Smart Porous Silicon Nanoparticles with Polymeric Coatings for Sequential Combination Therapy

Abstract

In spite of the advances in drug delivery, the preparation of smart nanocomposites capable of precisely controlled release of multiple drugs for sequential combination therapy is still challenging. Here, a novel drug delivery nanocomposite was prepared by coating porous silicon (PSi) nanoparticles with poly(beta-amino ester) (PAE) and Pluronic F-127, respectively. Two anticancer drugs, doxorubicin (DOX) and paclitaxel (PTX), were separately loaded into the core of PSi and the shell of F127. The nanocomposite displayed enhanced colloidal stability and good cytocompatibility. Moreover, a spatiotemporal drug release was achieved for sequential combination therapy by precisely controlling the release kinetics of the two tested drugs. The release of PTX and DOX occurred in a time-staggered manner; PTX was released much faster and earlier than DOX at pH 7.0. The grafted PAE on the external surface of PSi acted as a pH-responsive nanovalve for the site-specific release of DOX. In vitro cytotoxicity tests demonstrated that the DOX and PTX coloaded nanoparticles exhibited a better synergistic effect than the free drugs in inducing cellular apoptosis. Therefore, the present study demonstrates a promising strategy to enhance the efficiency of combination cancer therapies by precisely controlling the release kinetics of different drugs.

Quercetin‐Based Modified Porous Silicon Nanoparticles for Enhanced Inhibition of Doxorubicin‐Resistant Cancer Cells

“…A desired PSi‐based system should retain the loaded therapeutic agents within the porous nanostructure before reaching the targeted sites and further release the drug in a stimuli‐responsive manner, e.g., pH‐responsive. Several strategies have been investigated to construct a pH‐sensitive drug release nanosystem, i.e., by using a pH‐sensitive polymer coating/encapsulating or pH‐sensitive inorganic material gating . Despite the clear improvements in the developed nanosystems, quite often the processes require preloading the drug before the particle's surface modification or encapsulation.…”

Spatiotemporally and Sequentially-Controlled Drug Release from Polymer Gatekeeper–Hollow Silica Nanoparticles

“…The primary strategy to overcome MDR is co-administration of multiple drugs789. However, varying drug uptake and suboptimal drug concentrations in heterogeneous tumour environments limit the synergistic efficacy of administered drugs101112.…”

Biodegradable Periodic Mesoporous Organosilica (BPMO) Loaded with Daunorubicin: A Promising Nanoparticle‐Based Anticancer Drug

“…In addition, BPMO with protease sensitive bonds have been synthesized . BPMO possess all the advantageous features of pure inorganic MSN such as high surface area, large pore volume and fine control of the pore diameter . On the other hands, the organic groups confer degradability under biorelevant conditions thus contributing to the issue of safety of nanomaterials during clinical use.…”

“…[10] BPMO possess all the advantageous features of pure inorganic MSN such as high surface area, large pore volume and fine control of the pore diameter. [11][12] On the other hands, the organic groups confer degradability under biorelevant conditions thus contributing to the issue of safety of nanomaterials during clinical use. Uptake of BPMO into cancer cells and delivery of anticancer drugs such as camptothecin and doxorubicin have been reported.…”