Tumor-adapting and tumor-remodeling AuNR@dendrimer-assembly nanohybrids overcome impermeable multidrug-resistant cancer

Abstract

Herein, smart Au nanorod@dendrimer-assembly nanohybrids (AuNR@DA NHs) were developed for adapting sequential biological barriers and remodeling tumor permeability, thereby achieving multimodal enhancement of penetration and internalization in multidrug-resistant poorly-permeable tumors. The AuNR@DA NHs possessed well-defined hybrid nanostructures, high dimensional stability, improved photothermal conversion efficiency, multistage transformations and on-demand therapeutic delivery. The tumor-adapting NHs could surmount complicated physiological barriers through enzyme/redox/pH triple-responsive features with tumor-tunable size, interface and disintegration, allowing for tumor site-specific photothermal conversion. More importantly, locally NIR-induced hyperthermia production would remodel the permeability of the tumor tissue and cell membrane to further facilitate penetration and internalization of organic drugs and inorganic nanoparticles. Encouragingly, in vitro and in vivo antitumor treatments suggested that supramolecular hybrid fabrication of theranostic AuNR@DA NHs successfully provided overwhelming chemo-photothermal effects against impermeable multidrug-resistant cancer.