A Sequential Dual-Model Strategy Based on Photoactivatable Metallopolymer for On-Demand Release of Photosensitizers and Anticancer Drugs

The synergistic combination of chemotherapy and photodynamic therapy has attracted considerable attention for its enhanced antitumoral effects; however, it remains challenging to successfully delivery photosensitizers and anticancer drugs while minimizing drug leakage at off-target sites. A red-light-activatable metallopolymer, Poly(Ru/PTX), is synthesized for combined chemo-photodynamic therapy. The polymer has a biodegradable backbone that contains a photosensitizer Ru complex and the anticancer drug paclitaxel (PTX) via a singlet oxygen (O-1(2)) cleavable linker. The polymer self-assembles into nanoparticles, which can efficiently accumulate at the tumor sites during blood circulation. The distribution of the therapeutic agents is synchronized because the Ru complex and PTX are covalently conjugate to the polymer, and off-target toxicity during circulation is also mostly avoided. Red light irradiation at the tumor directly cleaves the Ru complex and produces O-1(2) for photodynamic therapy. Sequentially, the generated O-1(2) triggers the breakage of the linker to release the PTX for chemotherapy. Therefore, this novel sequential dual-model release strategy creates a synergistic chemo-photodynamic therapy while minimizing drug leakage. This study offers a new platform to develop smart delivery systems for the on-demand release of therapeutic agents in vivo.