An indicator-guided photo-controlled drug delivery system based on mesoporous silica/gold nanocomposites

Abstract

A mesoporous silica/gold (MSN/Au) nanocomposite was designed for photocontrolled drug delivery targeted specifically at tumor cells. The MSN/Au nanocomposite was composed of MSN-based drug carriers and gold nanoparticle (AuNP)-based indicators. While the MSN-based drug carrier was a mesoporous silica nanoparticle immobilized with photo-switchable azobenzene (Azo) moieties, the AuNP-based indicator was a fluorescence-quenched AuNP modified with a matrix metalloproteinase (MMP) substrate and poly(ethylene glycol). The two kinds of nanoparticles were connected by an α,β cyclodextrin (α,β CD) dimer "bridge." In vitro studies demonstrated that the nanocomposite specifically interacted with tumor sites overexpressing MMP-2, which enabled guidance of the subsequent UV light irradiation for releasing entrapped drugs. Through integration of the AuNP-based indicator and the MSN-based drug carrier, the MSN/Au nanocomposite could precisely localize the released drug to tumor sites, thereby significantly improving therapeutic efficacy.

Drug‐Loaded Mesoporous Tantalum Oxide Nanoparticles for Enhanced Synergetic Chemoradiotherapy with Reduced Systemic Toxicity

“…Among numerous types of nano‐DDSs, nanoparticles with mesoporous structures, for which mesoporous silica nanoparticles (MSNs) are a typical example, have been extensively explored owing to their unique porous structure and large surface area to enable efficient loading of different types of therapeutic or imaging molecules . In particular, MSN‐based nano‐DDSs have shown great promises in the delivery of different types of therapeutics (e.g., chemotherapy, gene therapy, and photodynamic therapy) as demonstrated in numerous preclinical animal experiments . However, as far as chemoradiotherapy is concerned, MSNs are used only as carriers for chemotherapeutic agents, and themselves have no significant sensitizing effect to radiotherapy on account of their weak X‐ray absorption.…”

Advances in Peptide Functionalization on Mesoporous Silica Nanoparticles for Controlled Drug Release

“…Most importantly, results indicated the feasibility of MMP‐9 mediated drug release in an advanced mouse model and human lung tissue using the new experimental setup of ex vivo 3D lung tissue cultures. Besides, to precisely control the release timing, location, and dosage of therapeutic agents in a photo‐controlled triggered DDS, our group reported that gold nanoparticles (AuNPs) functionalized with carboxyfluorescein‐conjugated MMP‐2 sensitive peptides (FAM‐GGPLGLAC) were used as the tumor indicator for the photo‐switchable azobenzene (Azo)‐functionalized MSN . As shown in Figure , once it arrived at tumor site, the cleaved GGPLGLAC peptide led to the recovery of green fluorescence (FAM) and could be used to guide the subsequent ultraviolet (UV)‐irradiation, which would transform trans‐Azo to cis‐Azo, the MSNs pores would be open and release the entrapped DOX at tumor site.…”

“…I) Tumor tissue overexpressed MMP‐2; II) specific cleavage of the MMP‐2 substrate peptide, leading to subsequent fluorescence recovery; III) fluorescence‐guided UV light irradiation and DOX release; IV) tumor cells killed by the released DOX. Reproduced with permission . Copyright 2014, Springer.…”

“…Meanwhile, Lin et al proposed the concept of “gatekeeper” and the guest molecules were blocked in the reservoir of MSNs by capping the pores with a gatekeeper . MSNs can be end‐capped with multitudinous gatekeepers, such as nanoparticles, supramolecular nanovalves, polymers, biomolecules, peptides, which can be triggered by internal stimuli or external stimuli including redox, pH, temperature, photo, enzymes, and magnetic signals . As we know, among these various gatekeepers, peptides are one of the most attractive types due to their inherent bioactivity, biodegradability and good biocompatibility .…”

Reversible Nanogate System for Mesoporous Silica Nanoparticles Based on Diels–Alder Adducts

“…This arrangement would block pore outlets to prevent the release of the payload, while also allowing the anchoring of targeting elements easily. Similar strategies have been employed successfully, as reported in the literature, through which coating with AuNPs has been performed through electrostatic deposition, cyclodextrin– adamantane supramolecular interactions, acid‐sensitive linkers, or displaceable DNA sequences . Notwithstanding the above disadvantages, all reported models suffer from a low Au to MSNs ratio, which does not ensure efficient capping, as observed from published TEM images.…”