skip to main content


This content will become publicly available on July 1, 2024

Title: Disulfide-Modified Mesoporous Silica Nanoparticles for Biomedical Applications
Mesoporous silica nanoparticles (MSNs) are highly porous carriers used in drug and gene delivery research for biomedical applications due to their high surface area, narrow particle size distribution, and low toxicity. Incorporating disulfide (SS) bonds into the walls of MSNs (MSN-SSs) offers a dual pathway for drug release due to the pore delivery and collapsing porous structure after cellular engulfment. This study explores the effect of embedding disulfide bonds into MSNs through various structural and biological characterization methods. Raman spectroscopy is employed to detect the SS bonds, SEM and TEM for morphology analyses, and a BET analysis to determine the required amount of SSs for achieving the largest surface area. The MSN-SSs are further loaded with doxorubicin, an anticancer drug, to assess drug release behavior under various pH conditions. The MSN-SS system demonstrated an efficient pH-responsive drug release, with over 65% of doxorubicin released under acidic conditions and over 15% released under neutral conditions. Cleaving the SS bonds using dithiothreitol increased the release to 94% in acidic conditions and 46% in neutral conditions. Biocompatibility studies were conducted using cancer cells to validate the engulfment of the nanoparticle. These results demonstrate that MSN-SS is a feasible nanocarrier for controlled-release drug delivery.  more » « less
Award ID(s):
1924412
NSF-PAR ID:
10463352
Author(s) / Creator(s):
; ; ; ; ;
Date Published:
Journal Name:
Crystals
Volume:
13
Issue:
7
ISSN:
2073-4352
Page Range / eLocation ID:
1067
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. null (Ed.)
    Tumor microenvironment responsive drug delivery systems are potential approaches to reduce the acute toxicity caused by high-dose cancer chemotherapy. Notwithstanding the conventional nano-drug delivery systems, the redox and pH stimuli drug delivery systems are currently gaining attention. Therefore, the current study was designed to compare three different covalent carbon dots (C-dots) systems based on doxorubicin (dox) release profiles and cancer cell viability efficacy under acidic and physiological conditions. The C-dots nanosystems that were examined in this study are directly conjugated (C-dots-dox), pH triggered (C-dots-HBA-dox), and the redox stimuli (C-dots-S–S-dox) conjugates. The drug loading content (DLC%) of the C-dots-S–S-dox, C-dots-HBA-dox, and C-dots-dox was 34.2 ± 0.4, 60.0 ± 0.3, and 70.0 ± 0.2%, respectively, that examined by UV-vis spectral analysis. The dox release paradigms were emphasized that all three conjugates were promisingly released the dox from C-dots faster in acidic pH than in physiological pH. The displayed highest dox released percentage in the acidic medium was 74.6 ± 0.8% obtained by the pH stimuli, C-dots-HBA-dox conjugate. When introducing the redox inducer, dithiothreitol (DTT), preferentially, the redox stimuli C-dot-S–S-dox conjugate demonstrated a faster dox release at acidic pH than in the pH 7.4. The SJGBM2 cell viability experiments revealed that the pH stimuli, C-dots-HBA-dox conjugate, displayed a significant cell viability drop in the artificially acidified pH 6.4 medium. However, in the physiological pH, the redox stimuli, C-dots-S–S-dox conjugate, was promising over the pH stimuli C-dots-HBA-dox, exhibiting cell viability of 60%, though its’ efficacy dropped slightly in the artificially acidified pH 6.4 medium. Moreover, the current study illustrates the stimuli conjugates’ remarkable efficacy on sustain drug release than direct amide linkage. 
    more » « less
  2. Carbohydrate-based low molecular weight gelators (LMWGs) are compounds with the capability to self-assemble into complex molecular networks within a solvent, leading to solvent immobilization. This process of gel formation depends on noncovalent interactions, including Van der Waals, hydrogen bonding, and π–π stacking. Due to their potential applications in environmental remediation, drug delivery, and tissue engineering, these molecules have emerged as an important area of research. In particular, various 4,6-O-benzylidene acetal-protected D-glucosamine derivatives have shown promising gelation abilities. In this study, a series of C-2-carbamate derivatives containing a para-methoxy benzylidene acetal functional group were synthesized and characterized. These compounds exhibited good gelation properties in several organic solvents and aqueous mixtures. Upon removal of the acetal functional group under acidic conditions, a number of deprotected free sugar derivatives were also synthesized. Analysis of these free sugar derivatives revealed two compounds were hydrogelators while their precursors did not form hydrogels. For those protected carbamates that are hydrogelators, removal of the 4,6-protection will result in a more water-soluble compound that produces a transition from gel to solution. Given the ability of these compounds to form gels from solution or solution from gels in situ in response to acidic environments, these compounds may have practical applications as stimuli-responsive gelators in an aqueous medium. In turn, one hydrogelator was studied for the encapsulation and release of naproxen and chloroquine. The hydrogel exhibited sustained drug release over a period of several days, with the release of chloroquine being faster at lower pH due to the acid lability of the gelator molecule. The synthesis, characterization, gelation properties, and studies on drug diffusion are discussed.

     
    more » « less
  3. Abstract

    The controlled release of drugs using nanoparticle‐based delivery vehicles is a promising strategy to improve the safety and efficacy of chemotherapy. A simple, scalable, and reproducible strategy is developed to synthesize a drug delivery system (DDS) by loading 6‐maleimidocaproyl‐hydrazone doxorubicin (DOX‐EMCH) into the empty core of virus‐like particles (VLPs) derived from Physalis mottle virus (PhMV) via a combination of chemical conjugation to cysteine residues and π–π stacking interactions with the anchored doxorubicin molecule. The DOX‐EMCH prodrug features an acid‐sensitive hydrazine linker that triggers the release of doxorubicin in the slightly acidic extracellular tumor microenvironment or acidic endosomal or lysosomal compartments following cellular uptake. The VLP external surface is coated with polyethylene glycol (PEG) to prevent non‐specific uptake and improve biocompatibility. The DOX‐PhMV‐PEG particles are stable in vitro and show greater efficacy in vivo compared to free doxorubicin in a breast tumor mouse model (using MDA‐MB‐231 cells and nude mice): 92% of the tumor‐bearing mice treated with DOX‐PhMV‐PEG are completely cured compared to 27% of those treated with free doxorubicin under the same conditions, representing a 3.4‐fold improvement. These results lay a foundation for the further development of this biological drug delivery system for a new generation of chemotherapy products.

     
    more » « less
  4. Abstract

    The progress of nanoparticle (NP)-based drug delivery has been hindered by an inability to establish structure-activity relationships in vivo. Here, using stable, monosized, radiolabeled, mesoporous silica nanoparticles (MSNs), we apply an integrated SPECT/CT imaging and mathematical modeling approach to understand the combined effects of MSN size, surface chemistry and routes of administration on biodistribution and clearance kinetics in healthy rats. We show that increased particle size from ~32- to ~142-nm results in a monotonic decrease in systemic bioavailability, irrespective of route of administration, with corresponding accumulation in liver and spleen. Cationic MSNs with surface exposed amines (PEI) have reduced circulation, compared to MSNs of identical size and charge but with shielded amines (QA), due to rapid sequestration into liver and spleen. However, QA show greater total excretion than PEI and their size-matched neutral counterparts (TMS). Overall, we provide important predictive functional correlations to support the rational design of nanomedicines.

     
    more » « less
  5. Abstract

    Non‐spherical stimuli‐responsive polymeric particles have shown critical importance in therapeutic delivery. Herein, pH‐responsive poly(methacrylic acid) (PMAA) cubic hydrogel microparticles are synthesized by crosslinking PMAA layers within PMAA/poly(N‐vinylpyrrolidone) hydrogen‐bonded multilayers templated on porous inorganic microparticles. This study investigates the effects of template porosity and surface morphology on the PMAA multilayer hydrogel microcube properties. It is found that the hydrogel structure depends on the template's calcination time and temperature. The pH‐triggered PMAA hydrogel cube swelling depends on the hydrogel's internal architecture, either hollow capsule‐like or non‐hollow continuous hydrogels. The loading efficiency of the doxorubicin (DOX) drug inside the microcubes is analyzed by high‐performance liquid chromatography (HPLC), and shows the dependenceof the drug uptake on the network structure and morphology controlled by the template porosity. Varying the template calcination from low (300 °C) to high (1000 °C) temperature results in a 2.5‐fold greater DOX encapsulation by the hydrogel cubes. The effects of hydrogel surface charge on the DOX loading and release are also studied using zeta‐potential measurements. This work provides insight into the effect of structural composition, network morphology, and pH‐induced swelling of the cubical hydrogels and may advance the development of stimuli‐responsive vehicles for targeted anticancer drug delivery.

     
    more » « less