A Golgi Apparatus-Targeted Photothermal Agent with Protein Anchoring for Enhanced Cancer Photothermal Therapy

Adv Healthc Mater. 2024 Mar 14:e2303749. doi: 10.1002/adhm.202303749. Online ahead of print.

Abstract

The Golgi apparatus (GA) is central in shuttling proteins from the endoplasmic reticulum to different cellular areas. Therefore, targeting the GA to precisely destroy its proteins through local heat could induce apoptosis, offering a potential avenue for effective cancer therapy. Herein, a GA-targeted photothermal agent based on protein anchoring is introduced for enhanced photothermal therapy of tumor through the modification of near-infrared molecular dye with maleimide derivative and benzene sulfonamide. The photothermal agent can actively target the GA and covalently anchor to its sulfhydryl proteins, thereby increasing its retention within the GA. Under laser irradiation, the heat generated by the photothermal agent efficiently disrupts sulfhydryl proteins in situ, leading to GA dysfunction and ultimately inducing cell apoptosis. In vivo experiments demonstrate that the photothermal agent can precisely treat tumors and significantly reduce side effects.

Keywords: Golgi apparatus targeting; cancer therapy; molecular photothermal agent; photothermal therapy; protein anchoring.