pH/NIR-Responsive Polypyrrole-Functionalized Fibrous Localized Drug-Delivery Platform for Synergistic Cancer Therapy

摘要

Localized drug-delivery systems (LDDSs) are a promising approach for cancer treatment because they decrease systematic toxicity and enhance the therapeutic effect of the drugs via site-specific delivery of active compounds and possible gradual release. However, the development of LDDS with rationally controlled drug release and intelligent functionality holds great challenge. To this end, we have developed a tailorable fibrous site-specific drug-delivery platform functionalized with pH- and near-infrared (NIR)-responsive polypyrrole (PPy), with the aim of cancer treatment via a combination of photothermal ablation and chemotherapy. First, a paclitaxel (PTX)-loaded polycaprolactone (PCL) (PCL-PTX) mat was prepared by electrospinning and subsequently in situ membrane surface-functionalized with different concentrations of PPy. The obtained PPy-functionalized mats exhibited excellent photostability and heating property in response to NIR exposure. PPy-coated mats exhibited enhanced PTX release in a pH 5.5 environment compared to pH 7.4. Release was further accelerated in response to NIR under both conditions; however, superior release was observed at pH 5.5 compared to pH 7.4, indicating a dual stimuli-responsive (pH and NIR) drug-delivery platform. More importantly, the 808 nm NIR irradiation enabled markedly accelerated PTX release from PPy-coated PCL-PTX mats and slowed and sustained release following termination of laser irradiation, confirming representative stepwise drug-release properties. PPy-coated PCL-PTX mats presented significantly enhanced in vitro and in vivo anticancer efficacy under NIR irradiation compared to PPy-coated PCL-PTX mats not exposed to NIR or uncoated mats (PCL-PTX). This study has thus developed a promising fibrous site-specific drug-delivery platform with NIR- and pH-triggering that notably utilizes PPy as a dopant for synergistic photothermal chemotherapy.