A Nanotheranostic System Combining Lysosomal Cell Death and Nuclear Apoptosis Functions for Synergistic Cancer Therapy and Addressing Drug Resistance
Youmei Li, Qian Wu, Dan Li, Jiachang Huang, Haifei Wen, Yi Wu, Dong Wang, Ben Zhong Tang
Abstract
Abstract The lysosome is a prominent and crucial target for actualizing anticancer therapy due to the outstanding therapeutic effect of lysosomal cell death on apoptosis‐ and drug‐resistance cancer. Exploration of multifunctional materials involving lysosome‐targeting drugs for achieving efficient cancer treatment is definitely appealing, yet a significantly challenging task. Herein, a versatile nanotheranostic system allowing all cancer cell‐targeting, tumor microenvironment stimuli‐responsive, fluorescence imaging, lysosome‐targeting chemotherapy and nucleus‐targeting chemotherapy functions was tactfully designed and constructed, by encapsulating both doxorubicin and a lysosome‐specific targeting drug with aggregation‐induced emission features in functional amphiphilic polymers. Both in vitro and in vivo studies revealed that the presented nanotheranostic system exhibited synergistic anticancer therapy effects, negligible systemic toxicity, and remarkable inhibition of drug‐resistant cancer cells. This study thus brings a new insight into the development of a superior effective protocol for practical cancer treatment.