PH/hypoxia programmable triggered cancer photo-chemotherapy based on a semiconducting polymer dot hybridized mesoporous silica framework.

Da Zhang,Haiyan Sun,Zuwu Wei,Zhixiong Cai,Naishun Liao,Shanyou Lan,Juan Li,Ming Wu,Xiaolong Liu

doi:10.1039/c8sc02408a

Abstract

Although photothermal therapy (PTT) has become a compelling strategy for cancer therapy, few studies concern the physiological consequences of PTT ablation. Herein, we discover that PTT-induced hyperthermia can aggravate tumor hypoxia, which may increase the risk of tumor recurrence and reduce PTT efficacy. We thus integrated the pH/hypoxia-triggered Fe(iii)-banoxantrone (AQ4N) prodrug and semiconducting polymer dots (SPs) for programmable triggered cancer photothermal-chemotherapy. A SP-hybridized mesoporous silica framework, decorated by dopamine and polyethylene glycol, named PPMSF, was synthesized by a simple method, and then served as an efficient photo-absorbing agent (PTA) and drug carrier. Fe(iii)-AQ4N and Mn(ii) were then coordinated with PPMSF (abbreviated Mn-APPMSF) via coordination effects. The nanohybrids exhibited tumor micro-environment pH triggered drug release. Under the irradiation of NIR light, magnetic resonance imaging (MRI) tracked the accumulation of the nanohybrids in tumors which then destroyed tumor cells by local hyperthermia, this can consequently aggravate the tumor hypoxia levels. Intriguingly, the aggravated hypoxia can further enhance the reduction of AQ4N to significantly improve therapeutic efficacy and effectively inhibit tumor growth when compared with traditional PTT. These results indicate the potential of our nanohybrids as a programmable synergistic agent for cancer therapy.

Highlights

Cancer is recognized as a systematic disease rather than a solo abnormality
PCPDTBT dots (SPs) were prepared by nanoprecipitation according to previously reported works.[18,19,20,21,22,23]
A erwards, the hydrophobic semiconducting polymer dots (SPs) were encapsulated into the inner core of cetyltrimethyl ammonium chloride (CTAC, as a template) by a self-assembly method in an alkaline environment for 1 h through hydrophobic interactions, subsequently tetraethylorthosilicate (TEOS, as a silicon source) was gently added to the above mixture at 80 C for condensation around the CTAC template

Summary

Introduction

Cancer is recognized as a systematic disease rather than a solo abnormality. Different types of benign cells surround the milieu of a tumor and actively facilitate malignant progression in a three-dimensional structure.[1]. The HepG2 cells were incubated with PMSF, PPMSF and MnAPPMSF with/without laser irradiation (670 nm, 1 W cmÀ2) in aerobic or hypoxic conditions, respectively.

Results

Conclusion