Stimulated Release of Size‐Selected Cargos in Succession from Mesoporous Silica Nanoparticles

Abstract

Combination drug therapy, [1] a regimen in which multiple drugs with different therapeutic outcomes are used in parallel or in sequence, has become one of the dominant strategies in the clinical treatment of HIV/AIDS, [2] diabetes, [3] and cancer. [4] In cancer therapy, for example, the U.S. Food and Drug Administration (FDA) approved the use in 2006 of Avastin in combination with Carboplatin and Paclitaxel for the initial systemic treatment of patients with lung cancer. Unlike monotherapy, combination therapy maximizes ther-apeutic efficacy against individual targets and is more likely to overcome drug resistance, while increasing the odds of a positive prognosis and reducing harmful side effects.Drug delivery systems, which administer medically active compounds to diseased cells in a targeted and controlled manner, [5] have gained much attention in the past couple of decades. While polymers, [6] dendrimers, [7] micelles, [8] vesicles, [9] and nanoparticles [10] have all been investigated for their use as possible drug delivery systems, most systems provide either delivery of a single drug or the simultaneous delivery [11] of multiple drugs. Using these systems, however, it is difficult to control [12] the administration order, timing, and dosage of each individual drug in a comprehensive manner. While it is possible to deliver a cocktail of drugs using several different co-administered drug delivery systems, this protocol has disadvantages. For example, it is not easy to expose several co-administered drug delivery systems to the same target at the right time, while also controlling the dosage rates and ratios of each individual drug. In order to administer chemotherapeutic combinations and produce synergistic actions, well-organized multidrug release systems, which can provide combination therapies by controlling the release behavior of each drug individually, need to be invented.Mesoporous silica nanoparticles (MSNs) have attracted widespread interest [13] in the past decade for use in integrated functional systems. They have large surface exteriors and porous interiors that can be harnessed as reservoirs for smallmolecule-drug storage. These MSNs are nontoxic to cells and can undergo cellular uptake [14] into acidic lysosomes by endocytosis when they are 100-200 nm in diameter, thus making them a popular candidate [15] for drug delivery systems. In particular, MSNs can be functionalized with molecular, as well as supramolecular, switches in order to control the release of drug molecules in response to external stimuli. Oncommand release systems, which respond to a range of stimuli, including pH changes, [16] light initiation, [17] competitive binding, [18] redox activation, [19] biological triggers, [20] and temperature changes, [21] have been reported by us and others. To the best of our knowledge, however, all the on-command release systems reported to date cannot release multiple drugs in a step-by-step fashion.Cyclodextrins (CDs), because of their abilities to form inclusion complexes with guest molecul...

Photoexpulsion of Surface-Grafted Ruthenium Complexes and Subsequent Release of Cytotoxic Cargos to Cancer Cells from Mesoporous Silica Nanoparticles

“…20 Silica nanoparticles with good biocompatibility are an ideal platform for biomedical applications 21 because they have robust and well-defined structures for functionalization with multiple labels, targeting or therapeutic agents, 22 and the ability to release a drug under specific conditions such as pH changes, 23 photonic signals, 24 redox activation, 25 or biological triggers. 26,27 The present work is a proof-of-concept demonstration of such a platform technology involving the marriage of an octahedral ruthenium(II) complex and inorganic nanoparticles, namely, MSNPs.…”

Activation of Snap-Top Capped Mesoporous Silica Nanocontainers Using Two Near-Infrared Photons

“…3, 14–17 Commonly used functionalizations include polymers attached to the outer surface, 14, 18 incorporation of molecules into the framework, 3, 7, 14, 19 and attachment of molecules including nanomachines around the pore openings. 15, 16, 20, 21 The latter derivatized particles can deliver drugs using various stimuli. 13 Several examples of photoactivated 2–4, 6, 7, 22–24 drug release from MSNs and snaptop 14, 21, 25, 26 caps have been reported.…”

Pillar[6]arene-Valved Mesoporous Silica Nanovehicles for Multiresponsive Controlled Release

“…■ ASSOCIATED CONTENT * S Supporting Information Synthesis details and 1 H and 13 C NMR characterizations, TEM and SEM images, XRD, nitrogen adsorption−desorption isotherms and pore size distributions, TGA, zeta potentials, 1 H NMR, 13 C NMR, FTIR, and UV−vis spectra. This material is available free of charge via the Internet at http://pubs.acs.org.…”

“…The MSN vehicles capped with supramolecular nanovalves have been extensively studied, in which cyclodextrins, 8−13 calixarenes, 14,15 and cucurbiturils 16−24 encircled the thread-like molecules immobilized on the MSN surface. The nanovalves can be activated for controlled release with a variety of stimuli, such as pH, 8,13,[16][17][18]20,23,24 redox, 13,19 light, 15,22 enzyme, 10,11,14,21 and competitive binding 20,21 in aqueous solutions.…”