Polydopamine-Based Multifunctional Antitumor Nanoagent for Phototherapy and Photodiagnosis by Regulating Redox Balance

Abstract

The development of multifunctional nanoagents for the simultaneous achievement of high diagnostic and therapeutic performances is significant for precise cancer treatment. Herein, we report on a polydopamine (PDA)-based multifunctional nanoagent, <b>PML</b>, in which the methylene blue (MB) photosensitizer (PS) and l-arginine (l-Arg) tumor-targeting species are equipped. After selectively accumulating in tumor sites, glutathione (GSH)-responsive <b>PML</b> degradation can controllably release loaded MB to produce singlet oxygen (¹O₂) under near-infrared (NIR) photoirradiation. This GSH-depleted PS release process can not only weaken the body's antioxidant defence ability but also synergistically increase the ¹O₂ concentration. Therefore, GSH depletion-enhanced photodynamic therapy (PDT) efficiency is logically achieved by regulating the intracellular redox balance. In addition, our nanoagent can guide photoacoustic/NIR thermal dual-modal imaging and convert light into heat for cooperative cancer phototherapy because of the inherent photothermal conversion nature of PDA. As a result, excellent <i>in vivo</i> antitumor phototherapy (PDT + PTT) is achieved under the precise guidance of dual-modal imaging. This work not only realizes the integration of cancer diagnosis and treatment through PDA-based nanocarriers but also delivers dimensions in designing the next generation of multifunctional antitumor nanoagents for enhanced phototherapy and photodiagnosis by regulating the redox balance.