Journal Article

Chiral polymer modified nanoparticles selectively induce autophagy of cancer cells for tumor ablation

Qi, Xiaowei, Yuan, Long, Deng, Jun, Yang, Yongjun, Zhang, Fan, Yan, Chang, Jiang, Jun

2018

Overview

Background Autophagy regulation through exogenous materials has aroused intensive attention to develop treatment protocols according to diverse human diseases. However, to the best of our knowledge, few examples have been reported to selectively control autophagy process and ultimately achieve efficient therapeutic potential. Results In this study, monolayers of poly (acryloyl- l , d and racemic valine) ( l -PAV-AuNPs, d -PAV-AuNPs and l / d -PAV-AuNPs) chiral molecules were anchored on the surfaces of gold nanoparticles (PAV-AuNPs), and the subsequent chirality-selective effects on autophagy activation were thoroughly studied. The cytotoxicity induced by PAV-AuNPs towards MDA-MB-231 cells (Breast cancer cells) was achieved mainly through autophagy and showed chirality-dependent, with d -PAV-AuNPs exhibiting high autophagy-inducing activity in vitro and in vivo. In contrast, the PAV-AuNPs exhibited autophagy inactivation for normal cells, e.g., 3T3 fibroblasts and HBL-100 cells. The chirality-selective autophagy activation effect in MDA-MB-231 cells was likely attributed to the chirality-variant ROS generation, cellular uptake and their continuous autophagy stimulus. Furthermore, the intratumoral injection of d -PAV-AuNPs could largely suppress the tumor growth but exhibit negligible toxicity in vivo. Conclusions As the first exploration on stereospecific NPs for autophagy induction, this work not only substantiates that chiral polymer coated NPs can selective induce autophagy-specific in cancer cells and achieve a high tumor eradication efficiency in vivo, but also opens up a new direction in discovering unprecedented stereospecific nanoagents for autophagy-associated tumor treatment.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Ablation / Ablation (Surgery) / Acrylates - chemistry / Activation / Animals / Antineoplastic Agents - chemistry / Antineoplastic Agents - pharmacology / Antineoplastic Agents - therapeutic use / Apoptosis - drug effects / Autophagy / Autophagy - drug effects / Biocompatibility / Biotechnology / Breast cancer / Cancer / Cancer therapies / Care and treatment / Cell Line, Tumor / Cell Survival - drug effects / Chemistry / Chemistry and Materials Science / Chiral polymer / Chirality / Cytotoxicity / Deactivation / Drug resistance / Fibroblasts / Gold / Gold - chemistry / Health aspects / Heterografts / Humans / Inactivation / Kinases / Medical research / Medical treatment / Medicine, Experimental / Metal Nanoparticles - chemistry / Metal Nanoparticles - therapeutic use / Mice, Inbred BALB C / Mice, Nude / Molecular Medicine / Nanomaterials / Nanomedicine / Nanoparticles / Nanotechnology / Particle Size / Phagocytosis / Polymer coatings / Polymers / Polymers - chemistry / Proteins / Reactive Oxygen Species - metabolism / Stereoisomerism / Surface Properties / Technology application / Tissue Distribution / Toxicity / Tumor ablation / Tumors / Valine / Valine - analogs & derivatives / Valine - chemistry