Mesoporous Silica Nanoparticles in Biomedicine: Design Strategies, Functional Applications, and Safety Considerations for Advanced Drug Delivery Systems

In recent decades, the swift progress in materials science, together with significant improvements in experimental and analytical methodologies, has greatly broadened the scope of nanotechnology and deepened its scientific understanding. Nanomaterials have found extensive applications across multiple disciplines, including biomedical science, where they are used in drug development and disease diagnosis [1], physical sciences for advanced material engineering [2], and agricultural systems for improving crop productivity and protection [3]. This increasing interest has encouraged a large number of researchers to investigate the multifunctional potential of nanoscale materials. As a result, a wide variety of nanomaterials with distinct physicochemical properties, structural characteristics, and functional behaviors have been developed and optimized for application in diverse technological and biomedical fields [4–6].

Preclinical animal studies have demonstrated that several inorganic non-metallic nanomaterials, including graphene-based structures [7], carbon quantum dots [8], and mesoporous silica systems [9], exhibit considerable promise for biomedical use due to their favorable compatibility with biological systems. In particular, nanoparticles and layered double hydroxides (LDHs) have emerged as highly effective platforms for drug delivery applications. Copper carbonate nanoparticles, functioning as biomineralized carriers, have demonstrated high drug encapsulation efficiency along with pH-sensitive release behavior, enabling targeted delivery of therapeutic agents such as glucose oxidase and DNAzymes specifically to tumor microenvironments. These nanocarriers are capable of traversing biological barriers efficiently and releasing their payload under acidic tumor conditions, thereby improving therapeutic efficacy in oncological treatments [10–13]. Similarly, cobalt hydroxide nanosheets have exhibited selective toxicity toward malignant cells while simultaneously inhibiting metastatic cell migration, highlighting their potential role in anti-cancer strategies [10–13]. Furthermore, these two-dimensional nanostructures function effectively as delivery platforms that enhance cellular targeting and controlled release of therapeutic compounds.

In regenerative medicine, layered double hydroxides have attracted significant attention due to their high loading capacity and controllable release kinetics. These properties make them particularly suitable for applications in tissue repair, including bone regeneration, cartilage reconstruction, and skin healing, where they can deliver therapeutic molecules in response to specific physiological environments. Additionally, advancements in tricalcium silicate-based injectable cement systems, although not strictly classified as nanomaterials, illustrate how structurally engineered biomaterials can also function as effective drug delivery platforms, particularly within regenerative medical applications. Collectively, these findings emphasize the crucial role of nanomaterials in overcoming limitations of conventional drug delivery approaches, improving targeting precision, and enhancing therapeutic outcomes in fields such as oncology and tissue engineering [10–13].

Among the various nanostructures investigated, mesoporous silica nanoparticles (MSNs) have gained considerable attention due to their unique physicochemical and structural properties [14–15]. These materials are typically synthesized from amorphous mesoporous silica, which consists of silicate tetrahedral networks stabilized by covalent bonding interactions. This highly ordered porous architecture provides MSNs with exceptionally large surface areas and high drug-loading capacities, making them suitable for a wide range of biomedical applications including controlled drug delivery [14], targeted cancer therapy [15], and biosensing and fluorescence detection systems [16–20]. Although organic nanocarriers such as liposomes [21], exosomes [22], and polymeric micelles [23] generally exhibit superior biocompatibility compared to MSNs, their drug release behavior is often predominantly passive and dependent on systemic circulation dynamics, which limits their precision in targeted therapeutic applications [24–25].

In contrast, MSNs can be chemically functionalized through alkoxysilane-based surface modification strategies, enabling the development of gate-controlled nanocarriers with specific molecular recognition capabilities. This combination of internal porous architecture and external functionalization allows for controlled drug release, active targeting, and theranostic (therapeutic and diagnostic) applications. Consequently, mesoporous silica-based nanomaterials represent a highly promising platform for advancing precision medicine and biomedical engineering applications [26–34].

However, despite their significant advantages, several concerns have been raised regarding the biological safety of MSNs, particularly their potential cytotoxicity and inflammatory responses [34–36]. To enhance targeting specificity and improve gating mechanisms during MSN synthesis, researchers often modify nanoparticle surfaces with polymers or biological macromolecules, including monoclonal antibodies, to improve recognition and targeting efficiency [35–36]. Although such modifications enhance delivery performance, they may also increase particle size, molecular weight, and hydrodynamic diameter [37–39]. These changes can influence biodistribution and clearance mechanisms within the body.

Furthermore, prolonging circulation time is often a key design objective for improving therapeutic efficiency. However, the human endothelial and macrophage systems recognize foreign particles based on size and molecular weight characteristics [40], leading to rapid immune clearance. Surface-functionalized mesoporous silica materials may therefore exhibit increased immunogenicity, potentially triggering macrophage activation and cytokine release syndromes that disturb physiological homeostasis [41–44]. In addition, chemical surface modifications may introduce reactive functional groups or residual compounds that can contribute to cytotoxicity and tissue-level toxicity [45–46].

Moreover, current research on nano-silica materials lacks comprehensive tissue-specific evaluations across different organ systems [47]. Most existing studies remain focused on cellular-level observations, with insufficient systematic investigations addressing long-term biodegradation, cytotoxic effects, and tissue compatibility [48–51]. These limitations highlight the need for further in-depth in vivo studies to better understand the safety profile of MSNs.

Therefore, this review aims to systematically summarize the biomedical applications of mesoporous silica nanoparticles, particularly in drug delivery, cancer therapy, antibacterial strategies, and tissue regeneration. At the same time, it critically discusses their biological limitations, including potential cytotoxicity, biodegradation challenges, and immunological responses. By consolidating existing knowledge, this work provides a theoretical foundation for the future development and safer clinical translation of mesoporous silica-based nanomaterials.

Among the mesoporous silica nanoparticles (MSNs) that have been synthesized to date, MCM-41 is widely recognized as the most extensively studied and commonly utilized structure within the biomedical field. The conventional synthesis of MCM-41 typically involves tetraethyl orthosilicate (TEOS) as the silica precursor and cetyltrimethylammonium bromide (CTAB) as the structure-directing surfactant. These reactants are generally processed under alkaline conditions at approximately 80 °C, and the resulting products are obtained after several hours of reaction. However, it is frequently observed that residual surfactant molecules remain trapped within the mesoporous structure after synthesis. These residues may exhibit biological toxicity, and their incomplete removal can adversely affect the performance of MSNs in biological environments while simultaneously increasing biosafety concerns [1,2].

Therefore, post-synthesis purification is essential. Typically, the material undergoes high-temperature calcination at around 550 °C in a furnace or is alternatively subjected to acid reflux extraction to completely remove surfactant templates. This purification step yields the well-ordered hexagonal mesoporous structure characteristic of MCM-41, which generally exhibits pore sizes in the range of 2–3 nm [3]. In biomedical applications such as drug delivery and targeted molecular sensing, nanoparticles are required to possess small particle sizes while maintaining sufficiently large and tunable pore diameters. Accordingly, optimizing both particle size and pore architecture is critical to improving biological compatibility and functional performance. Recent studies have demonstrated that the incorporation of micelle-expanding agents during synthesis, along with precise control of precursor concentration, can significantly enhance porosity while maintaining nanoscale particle dimensions. This strategy improves drug loading efficiency and optimizes pharmacokinetic behavior of MSN-based systems [4,5].

Another important member of the M41S family is MCM-48, which has attracted substantial attention due to its unique three-dimensional bicontinuous cubic structure. Compared to MCM-41, MCM-48 offers improved mass transport properties and enhanced drug delivery potential because of its interconnected pore network. This architecture facilitates stronger interactions between drug molecules and cellular targets, thereby improving therapeutic efficiency. However, conventional synthesis methods for MCM-48 often require prolonged high-temperature reactions and the use of mixed cationic–anionic surfactant templates, resulting in relatively large particle sizes of approximately 1 µm. Such large dimensions are not ideal for in vivo applications, as they may trigger immune responses and potentially induce inflammatory cascades, including cytokine storms [6–8].

Recent progress has enabled the fabrication of monodisperse spherical MCM-48 nanoparticles with significantly reduced sizes ranging from 70 to 500 nm. These improvements have been achieved using modified Stöber synthesis approaches at room temperature, employing triblock copolymers such as Pluronic F127 as structure-directing agents. This advancement simplifies synthesis procedures and reduces particle size, thereby improving suitability for biomedical applications [9]. Nevertheless, the long-term biological safety and in vivo behavior of these smaller MCM-48 nanoparticles remain insufficiently investigated, and their interactions with complex biological systems are still not fully understood, posing important challenges for clinical translation [10,11].

In addition to MCM-41 and MCM-48, SBA-15 is another widely studied mesoporous silica material used in drug delivery applications. SBA-15 is typically synthesized under acidic conditions using triblock copolymers such as polyethylene oxide–polypropylene oxide (P123) as templates. Compared with MCM-41, SBA-15 generally exhibits larger pore diameters and improved structural stability. However, a notable limitation of SBA-15 is its relatively large particle size, which often remains in the submicron range. Such dimensions may restrict its ability to evade immune recognition, thereby limiting its effectiveness in systemic drug delivery applications. Reducing SBA-15 particle size to the nanoscale could significantly enhance its biomedical potential [12,13].

In addition, the surface charge density and hydrophobicity of mesoporous silica nanoparticles contribute to their tendency to aggregate in physiological environments, which compromises their monodispersity. Aggregation increases the likelihood of recognition by the immune system and may lead to interactions with blood components such as hemoglobin, resulting in deposition within the circulatory system and triggering inflammatory responses. To overcome these limitations, various surface engineering strategies such as ultrasonication, polymer coating, and chemical functionalization are employed to improve colloidal stability and reduce aggregation in biological fluids [14,15].

For example, Farooq et al. reported surface modification of MSNs with titanium dioxide coatings and subsequent loading with sodium nitroprusside, an antihypertensive agent. Their findings demonstrated that TiO?-modified MSNs exhibited improved dispersion stability and enhanced drug delivery efficiency. Moreover, such modifications extended circulation time within the bloodstream and improved targeted delivery performance [16,17].

Beyond conventional mesoporous silica nanoparticles, composite systems combining MSNs with other nanomaterials have emerged as a rapidly growing area of research due to their multifunctional capabilities. Among these, mesoporous silica–metal organic framework (MSN–MOF) composites have shown remarkable potential in biomedical applications. These hybrid materials combine high surface area, tunable pore structures, and excellent biocompatibility, making them highly suitable for drug delivery, imaging, and therapeutic applications. Their porous architecture allows efficient drug encapsulation and controlled release, thereby enhancing therapeutic efficiency and bioavailability [18–20].

Furthermore, MSN–MOF composites have demonstrated strong potential in biomedical imaging applications, including magnetic resonance imaging (MRI) and optical imaging, where they function as multifunctional contrast agents. In drug delivery systems, their structural tunability enables precise control over release kinetics, improving therapeutic outcomes. For instance, hollow MSN–MOF hybrids have been developed to achieve pH-responsive drug release, significantly enhancing cytotoxic effects against tumor cells while minimizing systemic toxicity [21–23].

The biocompatibility and biodegradability of these hybrid systems further support their application in biomedical fields. In addition, their multifunctional nature allows integration of diagnostic and therapeutic functions within a single platform, enabling theranostic applications. By incorporating magnetic nanoparticles or fluorescent agents, these systems can simultaneously perform imaging and drug delivery, improving diagnostic accuracy and treatment efficiency [24–27].

Moreover, stimulus-responsive mesoporous silica nanoparticles have attracted increasing attention in cancer therapy. In particular, pH- and reactive oxygen species (ROS)-responsive systems have been developed to achieve controlled drug release within tumor microenvironments. Since tumor tissues exhibit acidic conditions and elevated ROS levels, these systems enable selective and efficient drug release while minimizing damage to healthy tissues [28,29].

pH-responsive MSNs are particularly effective in cancer therapy because they remain stable in physiological conditions but degrade rapidly in acidic tumor environments, releasing their therapeutic payload. Similarly, ROS-responsive systems utilize tumor-associated oxidative stress to trigger drug release. Dual-responsive systems combining both pH and ROS sensitivity provide even greater precision, enabling synergistic release mechanisms that enhance anticancer efficacy while reducing systemic toxicity [30–34].

Finally, rapid developments in pharmaceutical sciences, chemistry, and traditional medicine have led to the discovery and synthesis of numerous new therapeutic agents. However, challenges such as antibiotic resistance, tumor heterogeneity, and insufficient tissue regeneration continue to limit conventional therapies. As a result, nanomaterial-based drug delivery systems have gained increasing attention. Mesoporous silica nanoparticles, in particular, have emerged as promising platforms due to their tunable physicochemical properties, modifiable surfaces, and high biocompatibility. They are widely applied in drug delivery, cancer therapy, antibacterial treatment, and tissue engineering, highlighting their broad potential in modern biomedical science [35–45].

Structure and Properties of Mesoporous Silica Nanoparticles

Mesoporous silica nanoparticles (MSNs) represent a highly advanced class of nanostructured materials that have attracted considerable attention in recent years due to their unique architectural features and multifunctional capabilities. These nanoparticles are composed of a silica-based framework that incorporates an organized arrangement of mesopores, typically within the size range of 2 to 50 nanometers. The presence of these uniformly distributed pores creates an interconnected internal network that significantly enhances the available surface area, enabling efficient adsorption, encapsulation, and controlled release of a wide variety of therapeutic agents. This structural organization is particularly advantageous in biomedical applications, where precise control over drug delivery is essential for improving therapeutic outcomes.

The synthesis of MSNs is most commonly achieved through template-directed sol–gel methods. In this process, silica precursors such as tetraethyl orthosilicate (TEOS) undergo hydrolysis and condensation reactions under controlled experimental conditions. Surfactants, including cetyltrimethylammonium bromide (CTAB) or triblock copolymers, act as structure-directing agents that self-assemble into micellar arrangements. These micelles serve as templates around which the silica framework is formed, resulting in highly ordered mesoporous structures. Following synthesis, the removal of the surfactant template—typically through calcination or solvent extraction—leads to the formation of well-defined porous channels. This approach enables precise control over structural parameters such as pore size, morphology, and particle dimensions, ensuring high reproducibility and uniformity, which are critical for nanomedicine applications [1,2].

The structural characteristics of MSNs include pore diameters ranging between 2 and 50 nm, particle sizes generally falling within 50 to 200 nm, and surface areas that can reach up to approximately 1000 m²/g. Additionally, these nanoparticles possess a large pore volume, which further contributes to their exceptional capacity for drug encapsulation. Such features allow MSNs to accommodate a wide spectrum of therapeutic molecules, ranging from small-molecule drugs to larger biomolecules such as proteins, peptides, and nucleic acids. The high internal surface area not only enhances drug loading efficiency but also provides numerous active sites for interaction between the drug molecules and the silica matrix.

One of the most significant advantages of MSNs lies in their tunable pore structure. By modifying synthesis conditions, including surfactant concentration, pH, and reaction temperature, researchers can precisely control pore size and distribution. This tunability allows MSNs to be customized for specific applications, enabling them to accommodate molecules of varying sizes and regulate drug release kinetics effectively. For example, smaller pores may be suitable for controlled release of low-molecular-weight drugs, while larger pores can facilitate the delivery of macromolecules such as enzymes or DNA.

In addition to their structural versatility, MSNs exhibit excellent chemical and thermal stability due to the presence of strong siloxane (Si–O–Si) bonds within the silica framework. These covalent bonds provide mechanical strength and resistance to degradation under physiological and environmental conditions, ensuring that the nanoparticles maintain their structural integrity during circulation in the body. This stability is crucial for ensuring consistent drug delivery performance and minimizing premature release of therapeutic agents.

Another important feature of MSNs is their relatively favorable biocompatibility. Silica is generally considered a safe material for biomedical use, and MSNs have demonstrated acceptable compatibility with biological systems when appropriately synthesized and modified. Their porous architecture not only facilitates drug encapsulation but also protects therapeutic agents from enzymatic degradation or chemical instability during circulation. As a result, MSNs can significantly enhance drug stability, prolong circulation time, and improve overall therapeutic efficacy. These characteristics make them particularly valuable in the treatment of complex diseases such as cancer, where targeted and controlled drug delivery is essential [1,3].

Physicochemical Properties

Mesoporous silica nanoparticles possess a distinctive combination of physicochemical properties that make them highly suitable for a wide range of biomedical applications. Among these properties, the exceptionally high specific surface area is one of the most important. With surface areas reaching up to 1000 m²/g, MSNs provide an extensive interface for drug adsorption and interaction. This feature significantly enhances drug loading capacity and allows for efficient encapsulation of therapeutic agents within the nanoporous structure.

The large pore volume of MSNs further contributes to their effectiveness as drug carriers. This characteristic enables the accommodation of various types of molecules, including hydrophilic and hydrophobic drugs, proteins, peptides, and nucleic acids. The ability to load diverse therapeutic agents makes MSNs highly versatile platforms for drug delivery applications. Additionally, the interconnected pore network facilitates efficient diffusion of molecules, ensuring controlled and sustained release of drugs over time [2,3]. Another key physicochemical property of MSNs is their tunable pore size and morphology. By adjusting synthesis parameters such as surfactant type, concentration, and reaction conditions, researchers can design nanoparticles with specific structural characteristics tailored to particular biomedical applications. This level of control enables the development of advanced drug delivery systems capable of achieving targeted and stimuli-responsive release.

The chemical stability of MSNs is primarily attributed to the siloxane bonds that form the backbone of the silica framework. These bonds provide resistance to chemical degradation and ensure structural stability under physiological conditions. As a result, MSNs can maintain their integrity during circulation in the bloodstream, preventing premature release of drugs and enhancing delivery efficiency. Surface chemistry is another critical aspect of MSNs. The presence of silanol (Si–OH) groups on the surface allows for easy functionalization with various chemical groups, polymers, and biomolecules. This capability enables the modification of surface properties to improve biocompatibility, targeting ability, and drug release behavior. For example, surface modification can enhance hydrophilicity, reduce aggregation, and improve interaction with biological membranes.

Biocompatibility is a crucial requirement for any nanomaterial intended for biomedical use. MSNs generally exhibit low toxicity and good compatibility with biological systems, particularly when their surface is appropriately modified. Functionalization strategies such as PEGylation can further improve their biocompatibility by reducing protein adsorption and immune system recognition. These modifications extend circulation time and enhance therapeutic efficacy. Overall, the combination of high surface area, large pore volume, tunable structure, chemical stability, and favorable biocompatibility makes MSNs highly promising candidates for advanced drug delivery systems and other nanomedicine applications [1,3].

Figure 1: Structure and Properties of Mesoporous Silica Nanoparticles

Types of Mesoporous Silica Nanoparticles

Mesoporous silica nanoparticles have been developed in a variety of structural forms, each with distinct characteristics that influence their performance in biomedical applications. These variations are primarily based on differences in pore arrangement, particle morphology, and structural organization.

One of the most widely studied types is MCM-41, which features a highly ordered hexagonal arrangement of one-dimensional cylindrical pores. This structure provides uniform channels that are well-suited for controlled drug release. The simplicity and uniformity of MCM-41 make it a popular choice for drug delivery applications. In contrast, MCM-48 exhibits a three-dimensional cubic pore structure with interconnected channels. This arrangement enhances molecular diffusion and improves drug release kinetics, making it more suitable for applications requiring rapid and efficient delivery of therapeutic agents. SBA-15 is another important type of MSN characterized by larger pore sizes and thicker silica walls. These features provide improved mechanical strength and thermal stability, making SBA-15 suitable for applications that require robust structural integrity. However, its larger particle size may limit its use in certain biomedical applications.

Hollow MSNs represent a more advanced structural design, featuring a central cavity surrounded by a porous shell. This configuration significantly increases drug loading capacity and allows for the simultaneous delivery of multiple therapeutic agents. The hollow structure also enables controlled release through the outer shell, providing additional flexibility in drug delivery strategies. Core–shell MSNs combine a functional core, such as magnetic or fluorescent materials, with a mesoporous silica shell. This design enables multifunctional applications, including simultaneous diagnosis and therapy (theranostics). The core can provide imaging or targeting capabilities, while the mesoporous shell serves as a drug carrier. These structural variations provide researchers with a wide range of options for designing customized nanocarriers tailored to specific biomedical applications, particularly in targeted cancer therapy [1,2,4].

Figure 2: Types of Mesoporous Silica Nanoparticles

 Synthesis Methods of Mesoporous Silica Nanoparticles

 Sol–Gel Method

The sol–gel method is the most commonly used technique for synthesizing MSNs due to its versatility and simplicity. In this process, silica precursors undergo hydrolysis and condensation reactions to form a three-dimensional silica network. Surfactants act as templates, guiding the formation of mesoporous structures. After removal of the template, a highly ordered porous material is obtained. This method allows precise control over particle size, pore diameter, and morphology, making it ideal for biomedical applications. Its reproducibility and scalability further contribute to its widespread use in research and industry [1,3].

Template-Assisted and Microemulsion Methods

Template-assisted synthesis involves the use of surfactants or polymers to direct the formation of specific pore structures. By adjusting synthesis conditions, researchers can achieve precise control over structural properties. The microemulsion method utilizes nanoscale droplets as confined reaction environments, resulting in highly uniform nanoparticles with narrow size distribution. This approach is particularly useful for applications requiring consistent pharmacokinetics [2].

Green Synthesis Approaches

Green synthesis methods focus on sustainability by using natural silica sources such as agricultural waste. These approaches reduce environmental impact and production costs while maintaining comparable material properties. They also support large-scale production and align with principles of green chemistry [5].

Surface Functionalization of Mesoporous Silica Nanoparticles

Surface functionalization plays a critical role in enhancing the performance of MSNs in biomedical applications. The presence of silanol groups allows for chemical modification with various functional groups, improving drug loading, stability, and targeting ability. Polymer coatings such as polyethylene glycol (PEG) are commonly used to improve circulation time and reduce immune system recognition. This modification enhances biocompatibility and increases therapeutic efficiency. Functionalization also enables the development of stimuli-responsive systems, where drug release can be triggered by environmental factors such as pH or redox conditions. Additionally, targeting ligands can be attached to achieve selective delivery to diseased tissues, improving treatment outcomes [2,4,5].

Figure 3: Synthesis methods of mesoporous silica nanoparticles

Drug Loading and Controlled Release Mechanisms

Drug Loading Strategies

Drug loading in MSNs is achieved through various interactions, including physical adsorption and chemical bonding. The porous structure allows efficient encapsulation of a wide range of therapeutic agents, improving stability and preventing premature degradation [1,3].

Controlled and Stimuli-Responsive Release

MSNs can be engineered to release drugs in response to specific stimuli, enabling targeted therapy. pH-responsive systems are particularly useful in cancer treatment, while other systems respond to temperature, light, or enzymes. These advanced mechanisms improve therapeutic precision and reduce side effects [4,5].

Application of Mesoporous Silica Nanoparticles in Tumor Therapy

In recent years, the global burden of malignant tumors has increased markedly, largely driven by environmental degradation and lifestyle-related stress factors, making cancer one of the leading threats to human health worldwide [1,2]. In response to this growing challenge, extensive efforts have been directed toward the development of chemotherapeutic agents for effective cancer management. However, tumor progression is often accompanied by evolutionary adaptations that enable cancer cells to develop resistance to drugs, including multidrug resistance, which significantly reduces the effectiveness of conventional therapies [3–5]. These limitations have severely hindered advances in oncological treatment strategies.

With the rapid growth of interdisciplinary research, nanotechnology has emerged as a promising alternative, particularly mesoporous silica nanoparticles (MSNs), which have demonstrated significant potential in cancer therapy. MSNs can function both as drug carriers and immune-modulating platforms, offering new opportunities for targeted and combination cancer treatments [6].

MSNs are typically composed of amorphous silica with particle sizes ranging from approximately 2 to 50 nm. They possess exceptionally high surface areas (up to ~1500 m²/g) and large pore volumes (~1 cm³/g), which allow efficient loading of therapeutic agents. Drug molecules can be released through their well-ordered porous network, enabling selective accumulation in tumor tissues, particularly within highly permeable tumor vasculature [7–9]. Additionally, MSNs can be chemically modified on their surfaces to improve targeting efficiency and biological compatibility, making them highly attractive as drug delivery platforms in oncology applications [10–12].

For instance, He et al. developed a selenium-loaded MSN system in which tetrasulfide bonds were incorporated into the silica framework to enhance degradability under intracellular reducing conditions. The nanocarrier is internalized in tumor cells with elevated glutathione levels, triggering degradation and controlled release of selenium compounds. This process generates reactive oxygen species, leading to oxidative damage in tumor cells, including membrane disruption and nuclear injury, ultimately inducing apoptosis in osteosarcoma cells [13].

Importantly, this system remains stable under normal physiological conditions, thereby minimizing toxicity to healthy tissues and improving selective tumor targeting. Similarly, Tsou et al. developed a diatomite-based MSN system doped with lanthanide particles (dMSN-EuGd), which enables both drug delivery and photodynamic therapy. Under near-infrared irradiation, this system produces reactive oxygen species that induce tumor cell death while simultaneously delivering fucoidan for chemotherapy against colorectal cancer cells. Experimental results demonstrated significantly reduced viability of HCT116 colon cancer cells, highlighting the effectiveness of MSN-based multimodal therapies [14].

Beyond drug delivery and combination therapy, MSNs have also gained attention in tumor immunotherapy. Unlike conventional chemotherapy, immunotherapy aims to activate the patient’s immune system to selectively target tumor cells while minimizing damage to healthy tissues [15]. This approach enhances cytotoxic T-cell activity, suppresses tumor angiogenesis, and regulates tumor-associated cytokine release [16–18]. Emerging immunotherapeutic strategies such as CAR-T cell therapy and immune checkpoint blockade have shown strong clinical potential, although their widespread application remains limited by cost, safety concerns, and developmental challenges [19–21]. To overcome these limitations, nanocarrier-based immunotherapy systems have been developed, including exosomes, liposomes, and MSNs [22–24]. Among them, MSNs are particularly attractive due to their large pore volume, tunable surface chemistry, and efficient loading capacity. For example, Yang et al. designed a hybrid nanoplatform consisting of gold nanorods embedded in MSNs loaded with doxorubicin (AuNR@MSN@Dox). This system induces immunogenic cell death, promoting the release of tumor-associated antigens and damage-associated molecular patterns, which activate dendritic cells, macrophages, and cytotoxic T lymphocytes to enhance anti-tumor immunity [25–27].

Additionally, this system incorporates DNA hairpin gate structures that respond to near-infrared-induced thermal effects from gold nanorods, enabling controlled drug release at tumor sites. This multifunctional design integrates photothermal therapy, chemotherapy, and immunotherapy into a single platform, significantly improving therapeutic outcomes while reducing systemic toxicity [28]. Furthermore, MSNs have been widely explored as nano-vaccine platforms for cancer prevention. These systems deliver tumor antigens and immune adjuvants to activate adaptive immune responses and generate memory T cells prior to tumor development, thereby providing long-term immunological protection [29]. For example, Cha et al. developed ultra-large pore MSNs loaded with Toll-like receptor 9 agonists, which effectively activated dendritic cells and induced strong immune surveillance, preventing tumor formation in experimental models [30].

Overall, MSNs represent a highly versatile platform in oncology, with applications ranging from drug delivery and photothermal therapy to immunotherapy and gene delivery. Their large pore structure and tunable surface chemistry enable synergistic therapeutic approaches [31–33]. However, challenges remain in terms of synthesis optimization, long-term biosafety, and control of physicochemical properties, which must be addressed before clinical translation becomes feasible [34–36].

Application of Mesoporous Silica Nanoparticles in Bacterial Therapy

Infectious diseases have historically posed a serious threat to human health and continue to significantly impact global mortality and morbidity. In response to bacterial infections, a wide range of antibiotic agents has been developed, each targeting specific bacterial structures or metabolic pathways [37–39]. However, since the 1980s, antibiotic discovery has slowed considerably, while bacterial resistance has continued to increase due to prolonged exposure to antimicrobial agents and environmental selection pressures [40,41].

Bacteria have evolved multiple resistance mechanisms, including enzymatic degradation or modification of antibiotics, reduced membrane permeability, and active efflux systems that expel drugs from bacterial cells [42–44]. These mechanisms enable pathogens to survive antibiotic exposure, proliferate within the host, and disrupt physiological homeostasis, posing serious risks to patient health.

To address these challenges, nanotechnology-based drug delivery systems have been developed to encapsulate antibiotics, improving targeted delivery, reducing enzymatic degradation, and enhancing intracellular accumulation within bacterial cells [45]. These approaches improve antibacterial efficiency and help overcome resistance mechanisms.

Among nanomaterials, mesoporous silica nanoparticles (MSNs) are particularly promising due to their tunable pore structure, high surface area, and ease of functionalization. Unlike organic nanocarriers, MSNs offer superior structural stability and controlled surface modification, making them highly suitable for antibacterial applications [46–48].

MSNs can be engineered into different morphologies, including spherical, rod-shaped, hollow, and core–shell structures, each offering distinct biological advantages. Hollow MSNs, for instance, provide high drug-loading capacity and are particularly effective for encapsulating macromolecular therapeutics such as proteins and nucleic acids [49,50]. These structural advantages make MSNs highly efficient antibacterial carriers.

Antibiotics can be loaded into the porous framework of MSNs through covalent or non-covalent interactions, protecting them from premature degradation and enhancing their stability. This also improves their ability to penetrate bacterial membranes and increases therapeutic efficacy while reducing toxicity to host tissues [51–53].

For example, Tabriz et al. synthesized silver-doped chitosan-modified MSNs loaded with meropenem and imipenem. This system generated reactive oxygen species within bacterial cells, damaging DNA and cellular structures, thereby enhancing antibacterial activity against Gram-negative bacteria [54].

Similarly, Aguilera-Correa et al. developed gelatin- and polymyxin-coated MSNs loaded with moxifloxacin and rifampicin for the treatment of methicillin-resistant Staphylococcus aureus. The system effectively disrupted bacterial biofilms and significantly enhanced antibacterial efficacy, particularly when used in combination therapy [55].

Despite these promising results, most studies remain limited to in vitro evaluations, and comprehensive long-term in vivo toxicity and biocompatibility assessments are still lacking. This represents a major barrier to clinical translation [56–58]. Furthermore, surface modification strategies often involve complex synthesis procedures, which may introduce unexpected biological interactions and potential cytotoxic effects [59].

Therefore, future research should focus on developing standardized synthesis protocols and improving long-term safety evaluations of MSNs. Interdisciplinary collaboration among chemists, materials scientists, and clinicians will be essential to translate MSN-based antibacterial systems into clinical and industrial applications, providing effective solutions to antibiotic resistance challenges [60–62].

Application of Mesoporous Silica Nanoparticles in Tissue Engineering

Tissue engineering represents a multidisciplinary field that combines principles of biomedical science with engineering strategies to promote tissue regeneration and repair, ultimately restoring the structural and functional integrity of damaged organs and systems. Despite significant progress, the complexity of tissue repair processes—particularly the involvement of multiple cytokines and signaling pathways—limits the effectiveness of single-component scaffolds in addressing diverse pathological conditions [1,2].

Advancements in materials science have significantly revitalized this field, particularly through the incorporation of nanomaterials into scaffold systems. Nanoparticles with diverse morphologies and functionalities can be integrated into biomaterial scaffolds to better replicate the natural cellular microenvironment and regulate the controlled release of cytokines essential for tissue repair [3–5].

Among various nanomaterials, mesoporous silica nanoparticles (MSNs) have attracted considerable attention due to their excellent biocompatibility and versatile surface chemistry. Through functionalization, MSNs can be engineered with a wide range of chemical groups, enabling both covalent and non-covalent interactions with scaffold matrices. These properties not only enhance scaffold performance but also reduce inflammatory responses in surrounding tissues, thereby improving overall biocompatibility. As a result, MSNs have emerged as highly promising candidates for applications in tissue engineering and regenerative medicine [6].

Bone regeneration remains one of the most extensively studied applications within tissue engineering. Although bone possesses an intrinsic capacity for self-repair through granulation tissue formation, the regenerated tissue often exhibits altered mechanical properties and reduced density. Tissue engineering strategies aim to overcome these limitations and improve clinical outcomes. Early studies dating back to the 1970s demonstrated that silicon plays a crucial role in bone formation, with elevated silicon levels observed in actively mineralizing regions [7]. Subsequent animal studies further confirmed that silicon supplementation enhances cartilage hydration, promotes ossification, and improves compressive strength [8,9]. These findings provided a strong scientific basis for the application of silica-based materials in bone regeneration.

Building on this foundation, Zhao et al. developed cobalt-doped mesoporous silica-coated magnetic nanoparticles (Co-MMSNs) and evaluated their performance in large bone defect models. Their results demonstrated that these nanoparticles significantly enhance osteogenesis by promoting angiogenesis-related gene expression in bone marrow mesenchymal stem cells. This process accelerates granulation tissue formation and improves bone healing outcomes, highlighting the potential of MSNs in orthopedic applications [10].

In addition to structural support, effective delivery of bioactive molecules is essential for tissue regeneration. Direct incorporation of growth factors into scaffolds often leads to uncontrolled release, negatively affecting pharmacokinetics and therapeutic efficiency [11]. MSNs offer a solution by serving as controlled drug delivery systems, enabling sustained and targeted release of bioactive compounds. For example, Gong et al. developed a chitosan-gated MSN system loaded with naringin, a natural flavonoid with osteogenic properties. This nanocarrier prolongs the half-life of naringin, inhibits osteoclast activity, and enhances bone formation by suppressing NF-κB and MAPK signaling pathways. Notably, this MSN-based system demonstrated superior therapeutic efficacy compared to free naringin, offering a promising strategy for bone regeneration therapies [12]. Despite these advancements, several challenges remain. Current research largely focuses on MSNs as drug delivery vehicles, while precise control over drug release kinetics remains difficult to achieve. Furthermore, insufficient attention has been given to the dynamic interactions between MSNs and biological systems, including cells and tissues over time. The in vivo behavior, degradation pathways, and long-term fate of MSNs are still not fully understood. Addressing these challenges will require advanced analytical approaches, including multimodal imaging and fluorescence-based tracking techniques, to better understand MSN behavior in biological environments [13–16].

Figure 4: Applications of Mesoporous Silica Nanoparticles