Modulating Cell Specificity and Subcellular Localization by Molecular Charges and Lipophilicity
Guangxue Feng, Can Wang, Chengjian Chen, Yutong Pan, Min Wu, Yuanbo Wang, Jie Liu, Bin Liu
Abstract
The precise treatment of cancer requires maximized lesion to cancer cells and minimized damage to normal cells; however, the current theranostic nanomaterials have limited generic theranostic specificity to cancer cells. Herein, as a proof of concept, a small-molecular system simultaneously possessing on-site fluorescence light-up feature, universal cancer cell selectivity, controllable subcellular localization, and activated therapeutic function is developed for cancer theranostics. These molecular probes are composed of photosensitizers (PSs) with the aggregation-induced emission (AIE) feature as the core and aliphatic chains containing lipophilic cations as the arms, which show fluorescence light-up upon entering cancer cells. The charges and lipophilicity of these light-up probes are fine-tuned by the number of lipophilic cations, which modulate their cancer cell selectivity and subcellular localization, where the synthesized AIE PS with four positive charges (TPETM-4+) shows the highest differentiation toward all tested cancer cells over normal ones; neutrally charged TPETM-2 with two arms stains the cytoplasm, TPETM-2+ with two positive charges stains the mitochondria, while TPETM-4+ labels the lysosome. Moreover, under light irradiation, TPETM-4+ exhibits specific photodynamic ablation toward cancer cells over normal ones. This study proposes a new approach to design delivery systems for generic cancer cell selectivity with subcellular localization control, which opens up new opportunities for precise cancer therapy.