Hybrid smart mesoporous silica nanoparticles for theranostics.

Clever combinations of different types of functional nanostructured materials will enable the development of multifunctional nanomedical platforms for multimodal imaging or simultaneous diagnosis and therapy. Mesoporous silica nanoparticles (MSNs) possess unique structural features such as their large surface areas, tunable nanometer-scale pore sizes, and well-defined surface properties. Therefore, they are ideal platforms for constructing multifunctional materials that incorporate a variety of functional nanostructured materials. In this Account, we discuss recent progress by our group and other researchers in the design and fabrication of multifunctional nanocomposite nanoparticles based on mesoporous silica nanostructures for applications to simultaneous diagnosis and therapy. Versatile mesoporous silica-based nanocomposite nanoparticles were fabricated using various methods. Here, we highlight two synthetic approaches: the encapsulation of functional nanoparticles within a mesoporous silica shell and the assembly of nanoparticles on the surface of silica nanostructures. Various nanoparticles were encapsulated in MSNs using surfactants as both phase transfer agents and pore-generating templates. Using MSNs as a scaffold, functional components such as magnetic nanoparticles and fluorescent dyes have been integrated within these systems to generate multifunctional nanocomposite systems that maintain their individual functional characteristics. For example, uniform mesoporous dye-doped silica nanoparticles immobilized with multiple magnetite nanocrystals on their surfaces have been fabricated for their use as a vehicle capable of simultaneous magnetic resonance (MR) and fluorescence imaging and drug delivery. The resulting nanoparticle-incorporated MSNs were then tested in mice with tumors. These in vivo experiments revealed that these multifunctional nanocomposite nanoparticles were delivered to the tumor sites via passive targeting. These nanocomposite nanoparticles served as successful multimodal imaging probes and also delivered anticancer drugs to the tumor site. With innumerable combinations of imaging modalities and drug delivery available within these vehicles, multifunctional nanocomposite nanoparticles provide new opportunities for clinical diagnostics and therapeutics.

In the early 1990s the discovery of the MCM-41 and the M41S family of mesoporous materials had open new era in the chemistry and biology. They have prominent application inbiotechnological, biomedical and heterogeneous catalysts. Mesoporous silica nanoparticles (MSNs) exhibit unique structural features like as their large surface areas, tunable pore sizes in nanometer and well-defined surface properties. MSN materials which are comprised of a honeycomb-like porous structure with hundreds of empty mesoporous channel that are able to encapsulate relatively large amounts of biomolecules. They are ideal candidate for constructing multifunctional materials that encapsulate a variety of functional nanostructured materials. Multifunctional MSN materials have become one of the most attractive areas in nanobiotechnology and nanomedicine for various disease diagnosis and therapy. Multifunctional MSN have been successfully developed as a multifunctional platform to deliver therapeutic and diagnostic agents. Multifunctional MSNs are a highly promising platform for intracellular controlled release of drugs. In this review we discuss the recent developments in design and fabrication of multifunctional mesoporous silica nanoparticles in as efficient drug delivery applications such as the site-specific delivery and intracellular controlled release of drugs.Abbreviations;APTES; 3-aminopropyl triethoxy sialne, ATP; Adenosine triphospahate, CD; cyclodextrinCPT; camptothecin, CS; Chitosan,CTAB; cyltrimethylammonium bromide,DNA; Deoxyribonucleic acid,DOX; doxorubicin,EDC; 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide,FD; fluorescein disodium,FSP;Fluroscent particle ,IBU;ibuprofen,MCM; mobil composition material, MPS; 3-trimethoxylsilyl propyl methacrylate, MS; mesoporous silica,MSN; mesoporous silica nanoparticle, MSNs; mesoporous silica nanoparticles,MSNP; mesoporous silica nanoparticle,NPS; nanoparticles;PFDTES;perfluorodecyltriethoxysilane, PAA; polyacrylic acid,PR;photo responsive,PMAA; polymethyl methacrylate,SBF; simulated body fluid,TEOS;tetraethyl orthosilicate,TUNA;Thio undecyl-tetraethyleneglycoestero-nitrobenzylethyldimethyl ammonium bromide.

Purpose: Modern methods of pancreatic cancer diagnosis and treatment are severely lacking and have failed to provide effectual treatment options for patients. The root cause of this inadequacy stems from the hypovascularized nature of pancreatic cancer, making traditional chemotherapeutics and cancer detecting contrast agents nearly obsolete. A potential solution for tumor-targeting difficulties is through the implementation of nanotechnology, specifically targeting ligand capped, theranostic nanoparticles. We hypothesize that silica based, mesoporous nanoparticles capped with the targeting ligand, urokinase plasminogen activator (UPA) will serve as theranostic agents for treatment and diagnosis of pancreatic cancer. Methods: Mesoporous, silica nanoparticles (MSNs) were synthesized through the covering of acetyl trimethylammonium bromide (CTAB) scaffolding with tetraethyl orthosilicate (TEOS) in an aqueous environment. Refluxing was later used to remove the CTAB scaffolding and construct the desired mesoporous structure of the nanoparticles. MSNs were chemically engineered to be sensitive to acidic pH, contain fluorescent dye, and utilize a protein targeting ligand UPA. Multiple characterization techniques were employed to analyze the synthesized MSNs including UV-Vis spectroscopy, Zeta Potential, and Transmission Electron Microscopy (TEM). Pancreatic cancer tumor cells, S2CP9 and S2VP10, were treated with UPA-targeted or no-ligand encapsulated MSNs at pH 7.4 and 6.5. Following treatment, cells were washed to remove unbound particles followed by particle visualization based upon fluorescent dyes rhodamine or indocyanine green. Alternatively, cells treated with indocyanine green (ICG) loaded MSNs were placed into a tissue phantom and viewed using the Multispectral Optoacoustic Tomography system (MSOT). Mice with S2CP9 orthotopic pancreatic tumors were i.v. injected with 100 μL of UPA-ICG loaded MSNs. Particle localization was conducted using MSOT after 4h post injection. Results: Zeta potential and UV-Vis analysis confirmed the MSNs chemical conjugation, attributing the MSNs properties of pH sensitivity and fluorescence. pH sensitivity tests on the MSNs displayed drug release quantities at pH 6.5 to be ∼x2 the quantities of pH 6.8 and 7.4. Fluorescence microscopy showed the MSN uptake into S2VP10 and S2CP9 cell lines, while NIH3T3 cells (negative control) showed less binding. Use of UPAR antibody on S2VP10 and S2CP9 cell lines (positive control) blocked cellular binding. In tissue phantoms, UPA-ICG loaded MSNs at pH 6.5 demonstrated 20X and 7X more cell signal than without ligand or at pH 7.4, respectively. In-vivo, UPA-ICG loaded MSNs were detected within the orthotopic pancreatic tumor. Conclusion: UPA targeted, pH sensitive MSNs were found to possess substantial tumor cell binding against multiple cell lines and demonstrate potential as a theranostic nanoparticle for pancreatic cancer. Citation Format: Dillon S. Pender, Anil Khanal, Michael E. Egger, Lacey R. McNally. Development of theranostic mesoporous silica nanoparticles for pancreatic cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1481. doi:10.1158/1538-7445.AM2015-1481

Protean mesoporous silica nanoparticles (MSNs) are propitious candidates over decades for nanoscale drug delivery systems due to their unique characteristics, including (but not limited to) changeable pore size, mesoporosity, high drug loading capacity, and biodegradability. MSNs have been drawing considerable attention as competent, safer and effective drug delivery vehicles day by day by their towering mechanical, chemical and thermal characteristics. Straightforward and easy steps are involved in the synthesis of MSNs at a relatively cheaper cost. This review reports Stober's synthesis, the first proposed synthesis procedure to prepare micron-sized, spherical MSNs, followed by other modifications later on done by scientists. To ensure the safety and compatibility of MSNs with biological systems, the hemocompatibility evaluation of MSNs using human red blood cells (RBCs) is a widely welcomed exercise. Though our main vision of this overview is to emphasize more on the hemocompatibility of MSNs to RBCs, we also brief about the synthesis and widespread applications of multifaceted MSNs. The strike of different parameters of MSNs plays a crucial role concerning the hemolytic activity of MSNs, which also has been discussed here. The inference is derived by centering some feasible measures that can be adopted to cut down or stop the hemolytic activity of MSNs in the future.

The synthesis of drug delivery systems based on surface-modified mesoporous silica hollow structures remains a huge challenge. In this paper, we have obtained hollow mesoporous silica nanoparticles (MSNs) by surfactant directed sol-gel assisted hydrothermal treatment. The MSNs have the inorganic-organic hybrid frameworks with uniform diameter distribution (260 nm), and their specific surface area, mesoporous size and pore volume are 540 m2 g−1, 3.7 nm, 0.58 cm3 g−1, respectively. It was proved that the preparation of hollow ethane-bridged nanospheres with two silicon source was due to the high crosslinking of the silicone interface and hydrothermal treatment, providing a new approach for the study of drug-loaded and controlled release behavior. Based on the synthesis of MSNs, MSNs were modified by methacryloxy propyl trimethoxyl silane (MPS) on the surface of MSNs. Then N-isopropylacryamide (NIPAM) and acrylic acid (AA) were grafted onto the surface of modified MSNs. The hollow ethane-bridged PNA–MSNs (poly (NIPAM-co-acrylic acid)-MSNs) with two silicon source were prepared successfully. Due to their distinctive hollow structure, PNA–MSNs demonstrated high drug encapsulation efficiency (70.4% ± 2.9%). The experiment results proved that the modified hollow nanoparticles not only had good biocompatibility and stability, but also possessed pH-/thermal-dual responsiveness in drug release.

Biomacromolecules, such as miRNA/siRNA and proteins, have been drawing increasing attention because of their powerful application in treating disease. These biomolecules open new treatment opportunities for diseases which were previously considered as untreatable by conventional approaches. However, the broad clinical utilization of biomacromolecules is hindered by inefficient cellular uptake. Therefore, a variety of materials have been developed as carriers for biomacromolecule delivery. These materials include gold nanoparticles, lipid-based carriers, polymer spheres and silica nanoparticles. Among these carriers, mesoporous silica nanoparticles (MSNs) are particularly attractive due to their large surface area for cargo adsorption, tuneable pore size to encapsulate large molecules, and adjustable particle size to facilitate cellular uptake. In order to efficiently load cargos, a surface functionalization of MSN is often necessary to introduce functional groups. The covalent chemical functionalization of MSN usually requires multiple complicated chemical reactions and introduces extra cytotoxicity to the carrier. In some cases, the MSN modified by this approach cannot release the cargo efficiently. To address these challenges, this PhD thesis has developed two strategies to functionalize MSN for biomacromolecule delivery. These strategies are: i) developing and optimizing covalent chemical functionalization to enable the controlled release of miRNA, and; ii) developing non-covalent biological functionalization of MSN by using binding peptides/proteins as linkers to conjugate carriers and cargos through non-covalent binding. In the first approach, a cleavable S-S linker was introduced to enable a controlled release of miRNA. The density of functional groups (amine groups) was optimized on the surface of a large pore MSN (LP-MSN) with a pore size of 17 nm and a particle size of 200 nm. Three molecular layers were covalently attached on the surface of LP-MSN sequentially, including: i) a layer of oligo-lysine that controls the density of amine groups; ii) a layer containing the S-S linker that enables the release of miRNA, and; iii) a final polylysine layer that can efficiently bind miRNAs. From 5 different surface structures, LP-MSN-Epoxy-Trilysine-DSP-PLL has been identified as the optimal carrier that shows minimum cytotoxicity to normal rat kidney (NRK) cells while possessing a relatively high loading capacity and a controlled release for miRNA delivery. In the second approach, a non-covalent biological functionalization of MSN was developed based on self-assembly of the silica binding peptides/protein. Both the bi-functional peptides and the silica binding protein (the L2 protein) have been evaluated for functionalization of LP-MSN as delivery vehicles of biomacromolecules. Three bi-functional peptides that can bind both silica and nucleic acids have been designed, and it was found that the LP-MSN-RGRRRRLSCRLLK₈ complex is most effective in delivering a Cy3 labelled miRNA into NRK cells, while no cytotoxicity was observed at the working concentration. The function of miR-29B delivered by LP-MSN-RGRRRRLSCRLLK₈ was demonstrated by determining the down-regulated protein genes using a quantitative polymerase chain reaction (qPCR). The potential of the silica binding protein, the L2 protein, for functionalization of silica particles, was confirmed by the successful uptake of the LP-MSN-L2 complex into NRK cells. To further explore the influence of MSN properties on the delivery system, a dendritic mesoporous silica nanosphere (DMSN) modified by bi-functional peptides was evaluated for miRNA delivery. Although the fabricated DMSN-peptide complex shows relatively higher cytotoxicity to NRK cells compared with the LP-MSN-peptide complex, Alexa647-labelled miRNA was successfully delivered by DMSN-RGRRRRLSCRLLK₈ into NRK cells. Fundamental studies were carried out on the non-covalent biological functionalization system. Quartz crystal microbalance (QCM) results have quantified the binding amounts of bi-functional peptides on silica surfaces and confirmed rapid adsorption of these peptides. Small angel neutron scattering characterization of the L2 protein on a silica nanoparticle has shown that the affinity of L2 with silica is not affected by a high ionic strength up to 2 M MgCl₂, suggesting that the interaction between the L2 protein and silica particle is not just a charge interaction. Live cell imaging on the cellular uptake of DMSNS-RGRRRRLSCRLLK₈-Alexa647 labelled miRNA into NRK cells was performed, and the results suggest a phagocytotic pathway for the cluster of carrier-cargo complexes entering NRK cells. In summary, this PhD research has demonstrated two complementary approaches for functionalization of MSN as advanced delivery vehicles of macromolecules. The non-covalent biological functionalization approach, in particular, can serve as a powerful tool to modify silica surfaces by the self-assembly of designed bi-functional peptides. The method offers a simple fabrication process while decreasing cytotoxicity. The evaluation and fundamental study of these delivery systems provides valuable information to guide the functionalization of MSN as next generation of delivery vehicles for biomacromolecules (e.g. miRNA and proteins).

Mesoporous silica nanoparticles (MSNs) have been proposed as DNA and drug delivery carriers, as well as efficient tools for fluorescent cell tracking. The major limitation is that MSNs enter cells regardless of a target-specific functionalization. Here we show that non functionalized MSNs, synthesized using a PEG surfactant-based interfacial synthesis procedure, do not enter cells, while a highly specific, receptor mediated, cellular internalization of folic acid (FOL) grafted MSNs (MSN-FOL), occurs exclusively in folate receptor (FR) expressing cells. Neither the classical clathrin pathway nor macropinocytosis is involved in the MSN endocytic process, while fluorescent MSNs (MSN-FITC) enter cells through aspecific, caveolae-mediated, endocytosis. Moreover, internalized particles seem to be mostly exocytosed from cells within 96 h. Finally, cisplatin (Cp) loaded MSN-FOL were tested on cancerous FR-positive (HeLa) or normal FR-negative (HEK293) cells. A strong growth arrest was observed only in HeLa cells treated with MSN-FOL-Cp. The results presented here show that our mesoporous nanoparticles do not enter cells unless opportunely functionalized, suggesting that they could represent a promising vehicle for drug targeting applications.

MCM-41, a type ofmesoporous silica nanoparticle, has garneredwidespread interests as a useful carrier for drug delivery whereinthe drug gets adsorbed into the pores of the carrier. To understandthe adsorption mechanism and release of the drug at the molecularlevel, in the current study, it was attempted to generate a computationalmodel for the loading of 5-fluorouracil (5-FU), a chemotherapeuticagent into surface-modified MCM-41. The molecular surface models ofthe mesoporous silica (MCM-41) nanoparticle with different surfacesubstitutions were created. In the first stage, molecular mechanics(MM) simulations were carried out to obtain the optimized surfacestructures. Subsequently, a 5-FU drug molecule in its different formswas docked on top of different MCM-41 surfaces to understand the adsorptionorientation and energetics. To further validate the results, moreaccurate quantum mechanical (QM) calculations were also carried out,and the energetics between the QM and MM calculations are found tobe similar. All the substitutions (−NH2, −CN,−COOH) except the methyl substitution exhibited favorable interactionscompared to the unsubstituted MCM-41 surface which was in accordancewith the experimental observations. The release rate of 5-FU fromMCM-41 and aminopropyl-substituted MCM-41 (MCM-NH2) wasstudied using molecular dynamics simulations which revealed that therelease rate of 5-FU from the MCM-NH2 surface was slowercompared to that of plain MCM-41. The detailed surface characteristicsand the adsorption energies from the molecular simulations correlatingthe loading capacity and release are reported in here.

Tumor accumulation of neutron-activatable holmium-containing mesoporous silica nanoparticles in an orthotopic non-small cell lung cancer mouse model

Mesoporous silica nanoparticles (MSNs) are promising drug carriers for use in cancer treatment owing to their excellent biocompatibility and drug-loading capacity. However, MSN's incomplete drug release and toxic bioaccumulation phenomena limit their clinical application. Recently, researchers have presented redox responsive mesoporous organosilica nanoparticles containing disulfide (S-S) bridges (ss-MONs). These nanoparticles retained their ability to undergo structural degradation and increased their local release activity when exposed to reducing agents. Disulfide-based mesoporous organosilica nanoparticles offer researchers a better option for loading chemotherapeutic drugs due to their effective biodegradability through the reduction of glutathione. Although the potential of ss-MONs in cancer theranostics has been studied, few researchers have systematically compared ss-MONs with MSNs with regard to endocytosis, drug release, cytotoxicity, and therapeutic effect. In this work, ss-MONs and MSNs with equal morphology and size were designed and used to payload doxorubicin hydrochloride (DOX) for liver cancer chemotherapy. The ss-MONs showed considerable degradability in the presence of glutathione and performed comparably to MSNs on biocompatibility measures, including cytotoxicity and endocytosis, as well as in drug-loading capacity. Notably, DOX-loaded ss-MONs exhibited higher intracellular drug release in cancer cells and better anticancer effects in comparison with DOX-loaded MSNs. Hence, the ss-MONs may be more desirable carriers for a highly efficient and safe treatment of cancer.

As a drug delivery system (DDS), traditional mesoporous silica nanoparticles (MSNs) suffer from bioaccumulation in vivo and premature drug release in systemic circulation due to low degradation rate and lack of protective gatekeeper. Herein, we developed a safe and intelligent DDS with characteristics of pH-responsive biodegradation and controlled drug release based on mesoporous silica composite nanoparticles (MSCNs) capped with ZnO quantum dots (ZnO QDs). Acidic degradable MSCNs were successfully synthesized by doping Ca2+ and PO43− into the MSNs’ framework. The in vitro doxorubicin hydrochloride (DOX) release was inhibited at neutral pH 7.4 but triggered significantly at pH 5.0 due to the dissociation of ZnO caps. The internalization behavior and cytotoxicity of 4T1 cells indicated MSCNs-ZnO could efficiently deliver DOX into the cells with significant antitumor activity. Such a DDS with pH-responsive biodegradation and controlled drug release has promising potential for cancer therapy.

Pseudomonas aeruginosa (PA) is one of the most common bacteria isolated from chronic wounds and burns. Its treatment is a challenge due to antimicrobial drug resistance and biofilm formation. In this context, this study aimed to perform the synthesis and full characterization of hybrid nanosystems based on mesoporous silica nanoparticles (MSNs) functionalized with a nicotinic ligand and silver chloride nanoparticles, both phenytoin sodium (Ph)-loaded and unloaded, to evaluate the antibacterial properties against three different strains of PA (including two clinical strains) in a planktonic state and as biofilms. Ph is a well-known proliferative agent, which was incorporated into the hybrid nanomaterials to obtain an effective material for tissue healing and prevention of infection caused by PA. The Ph-loaded materials promoted a quasi-complete inhibition of bacterial growth in wound-like medium and biofilm development, with values of 99% and 96%, respectively, with selectivity indices above the requirements for drugs to become promising agents for the topic preventive treatment of chronic wounds and burns.

Background\n Cancer is one of the main causes of death in the world. In recent years, many studies have been conducted on the usage of nanomaterials in cancer treatment. In previous studies, the anti-tumor effects of mesoporous silica nanoparticles (MSN) on cancer cells have been shown. The aim of this study was to evaluate the effect of MSN loaded with Hematoporphyrin (HpD) on the cell proliferation and invasion of MCF7 (Michigan Cancer Foundation-7) breast cancer cell line. The antioxidant effects of MSN loaded with HpD were also investigated.\n \n \n Methods\n In this study, using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, the proliferation and viability of cancer cells were studied after exposure to MSN loaded with HpD. The wound healing assay technique (migration test) was used for the assessment of cancer cells’ invasion. The antioxidant effects of MSN loaded with HpD were studied by DPPH (2,2-diphenyl-1-picrylhydrazyl) assay and FRAP (ferric reducing/antioxidant power) assay techniques.\n \n \n Results\n Our results showed that the viability and proliferation of breast cancer cell line MCF7 in the presence of silica nanoparticles loaded with hematoporphyrin (HpD) significantly declined (P = 0.02). After exposure to mesoporous silica nanoparticles (MSN) loaded with hematoporphyrin (HpD), the cancer cell invasion decreased (P = 0.025). Silica nanoparticles alone and loaded with hematoporphyrin (HpD) showed considerable cytotoxic activities against cancer cell lines (IC50 = 20 - 30 μg.mL-1). The most promising result was achieved for MSN loaded with hematoporphyrin (HpD) with the minimum IC50 value. It was found that the proliferation rate of MCF7 cells decreased after treatment with this compound in a dose-dependent manner. The assessments with DPPH assay and FRAP assay techniques showed that MSN and MSN loaded with HpD have antioxidant activities.\n \n \n Conclusions\n MSN loaded with HpD have an inhibitory effect on the growth of the MCF7 cell line. MSN alone and in combination with HpD have an inhibitory effect on cell invasion in the MCF7 cell line. MSN alone and loaded with HpD have antioxidant effects. These results indicate that MSN has the potential to be used in cancer treatment as a carrier for anticancer drugs.

Stimuli-responsive controlled drug delivery systems have attracted the attention of researchers in recent decades due to their potential application in developing efficient drug carriers that are responsive to applied stimuli triggers. In this work, we present the synthesis of L-lysine (an amino acid that combines both amine and carboxylic acid groups in a single unit) modified mesoporous silica nanoparticles (MS@Lys NPs) for the delivery of the anticancer bioactive agent (curcumin, Cur) to cancer cells. To begin, mesoporous silica hybrid nanoparticles (MS@GPTS NPs) with 3-glycidoxypropyl trimethoxy silane (GPTS) were synthesized. The L-lysine groups were then functionalized onto the mesopore channel surfaces of the MS@GPTS NPs through a ring-opening reaction between the epoxy groups of the GPTS and the amine groups of the L-lysine units. Several instrumental techniques were used to examine the structural properties of the prepared L-lysine-modified mesoporous silica nanoparticles (MS@Lys NPs). The drug loading and pH-responsive drug delivery behavior of MS@Lys NPs were studied at different pH levels (pH 7.4, 6.5, and 4.0) using curcumin (Cur) as a model anticancer bioactive agent. The MS@Lys NPs' in vitro cytocompatibility and cell uptake behavior were also examined using MDA-MB-231 cells. The experimental results imply that MS@Lys NPs might be used in cancer therapy as pH-responsive drug delivery applications.

Mesoporous silica nanoparticles (MSNs) are attractive drug delivery carriers, and green synthesis from biowaste offers an eco-friendly alternative to conventional methods. Unlike previous studies limited to a single precursor, this work systematically compares multiple biosources, including rice husk (RH), wheat husk (WH), wheat stalk (WS), oat husk (OH), oat stalk (OS), and horsetail (HT), and establishes a standardized route to evaluate precursor influence. Among the tested precursors, RH and HT produced the highest purity silica and were selected for MSN synthesis. The resulting MSNs showed well-defined mesoporosity, high surface area, and controlled pore sizes, confirmed by FTIR, XRD, BET, and HR-TEM with pH-responsive Dox release enhanced under acidic conditions. They were biocompatible with HDFs, HUVECs, and U87 cells, while Dox-loaded MSNs exhibited strong anticancer effects against U87 cells at low drug concentration. The second novelty lies in evaluating MSN cellular uptake under physiologically relevant conditions using a microfluidic platform that mimics blood circulation, in contrast to conventional static assays. Cellular uptake was analyzed in 2D cultures and 3D microfluidic models, incorporating both static and dynamic conditions using HUVECs and U87. Notably, the dynamic 3D model, which simulates blood circulation, significantly enhanced MSN uptake by HUVECs and U87 compared to static conditions. These results emphasize the importance of physiological flow in optimizing nanoparticle-based drug delivery. This study introduces a dual innovation by establishing a consistent, multi-biosource approach for green MSN synthesis and validating their drug delivery potential in a realistic dynamic microenvironment, bridging sustainable nanomaterial development with advanced preclinical testing.