Smart photo-enabled micelles for cancer therapy: Mechanisms, challenges, and innovations

Phototherapy is a promising cancer treatment modality with inherent advantages including precise spatiotemporal controllability and minimal invasiveness. Recent years have witnessed the rapid development of various light-responsive nanoplatforms for realizing enhanced phototherapy. As a prominent class of intelligent nanodrug delivery platforms, light-responsive micelles can well overcome the limitations of free anticancer drugs (e.g., poor water solubility, limited in vivo stability, significant off-target toxicity, and resistance induction in cancer cells), effectively target the tumor sites, and realize controlled drug release under light irradiation to achieve improved anticancer efficacy. This review focuses on the recent advances in the development of smart photo-enabled micelles for achieving improved cancer therapy. We systematically introduce 6 different types of photo-enabled micelles based on their respective photo-activation mechanisms, including photocleavage, photodynamic effect, photothermal effect, photoisomerization, photo-induced rearrangement, and photo-triggered reduction. For each mechanism, the most representative studies are introduced in detail, and the innovations as well as limitations are discussed in-depth. We hope that this review will have broad implications for the future advancement of novel photo-activated nanoplatforms for precision cancer therapy.