Smart nanoplatform for sequential drug release and enhanced chemo-thermal effect of dual drug loaded gold nanorod vesicles for cancer therapy

Falian Zhu,Zhiqiang Yu,Yaodong Jiang,Shuwen Liu,Lulu Cai,Guozhu Tan,Fei Ren,Yingtao Zhong

doi:10.1186/s12951-019-0473-3

Abstract

BackgroundThe combination of multiple chemotherapeutics has been used in the clinic for enhanced cancer chemotherapy, however, frequent relapse, chemo-resistance and side effects remains therapeutic hurdles. Thus, the development of co-delivery system with enhanced targeting and synergistic different modal treatments has been proposed as promising strategies for intensive improvement of the therapeutic outcomes.ResultsWe fabricated a nanocarrier based on gold nanorods (Au NRs), cRGD peptide-modified and multi-stimuli-responsive paclitaxel (PTX) and curcumin (CUR) release for synergistic anticancer effect and chemo-photothermal therapy (PTX/CUR/Au NRs@cRGD). The specific banding of cRGD to αvβ3 integrin receptor on the tumor cell surfaces facilitated the endocytosis of PTX/CUR/Au NRs@cRGD, and the near-infrared ray (NIR) further enhanced the drug release and chemotherapeutical efficiency. Compared to single drug, single model treatment or undecorated-PTX/CUR/Au NRs, the PTX/CUR/Au NRs@cRGD with a mild NIR showed significantly enhanced apoptosis and S phase arrest in three cancer cell lines in vitro, and improved drug accumulation in tumor sites as well as tumor growth inhibition in vivo.ConclusionsThe tumor targeted chemo-photothermal therapy with the synergistic effect of dual drugs provided a versatile strategy for precise cancer therapy.

Highlights

The combination of multiple chemotherapeutics has been used in the clinic for enhanced cancer chemotherapy, frequent relapse, chemo-resistance and side effects remains therapeutic hurdles
The typical 1H NMR peaks of mercaptoundecanoic acid (MUA)–poly(ethylene glycol) (PEG)–COOH are ascribed to a combination of those of MUA and H2N–PEG–COOH, showing the successful conjugation of MUA and H 2N– PEG–COOH (Additional file 1: Figure S1D)
We evaluated the synergist effect index (Additional file 1: Table S2); and the results showed that a synergistic effect was found between the chemotherapy and plasmonic photothermal therapy (PPTT) regardless of the cell types or the concentration of Au NRs

Summary

Introduction

The combination of multiple chemotherapeutics has been used in the clinic for enhanced cancer chemotherapy, frequent relapse, chemo-resistance and side effects remains therapeutic hurdles. Stimuli-responsive nanocarriers have been widely investigated as potential controllable drug-release and enhanced cancer-targeting drug delivery system (DDSs) in recent years [1,2,3]. The design system of combined PPTT with chemotherapy that acquires stimuli-responsive, resulting in tumor ablation and providing more opportunities for ondemand therapy [21]. To this end, a variety of Au NRs systems have been proposed for PPTT and carrying anticancer drugs, selectively released their payloads at the controlled NIR area, resulting in synergistic chemo and photothermo-therapeutic efficacy [22,23,24]

Methods

Results

Conclusion