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

Abstract

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 ( 1 O 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 1 O 2 for photodynamic therapy. Sequentially, the generated 1 O 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.

Efficient Tumor Eradication at Ultralow Drug Concentration via Externally Controlled and Boosted Metallic Iron Magnetoplasmonic Nanocapsules

“…It is worth highlighting the achieved results using only one ultralow drug dose by intravenous injection, which enabled the tumor ablation by combining the magnetic concentration and the photothermally boosted chemotherapeutic effects, especially if they are compared to other light and paclitaxel multimodal therapies, which required multiple injections and/or a much higher drug amount, i.e., between 13- and 3000-fold higher than the MAPSULES treatment (Table ). − …”

Recent advances in redox-responsive nanoparticles for combined cancer therapy

“…The β-aminoacrylate linkage undergoes fast oxidative degradation, resulting in the cleavage of ester bonds. 106,107 Following the mechanism, our group 108 synthesized a red-light-responsive metallopolymer with a biodegradable backbone structure containing a Ru complex as the photosensitizer and a chemo-drug paclitaxel (PTX) linked via 1 O 2 activatable aminoacrylate linker (Fig. 8a).…”

Biodegradable Ru-Containing Polycarbonate Micelles for Photoinduced Anticancer Multitherapeutic Agent Delivery and Phototherapy Enhancement

“…This polymer with direct coordination and photoactivation strategy is more advantageous than the Rucontaining polymer which released Ru complexes and anticancer drugs separately, because the drug was released in this system through breaking the ROS-sensitive linker, which consumed a certain amount of 1 O 2 and reduced the PDT effect. 53 Because of the favorable degradability and biocompatibility of polycarbonate backbones, facile synthesis via direct Ru−N coordination reaction, amplified phototherapy efficiency via combined treatment modalities, and enhanced tissue penetration depth via red light irradiation, poly(DCARu) presents an attractive option for in vivo phototherapy (Figure 1b).…”

“…In the conjugate, dichloroacetate acid (DCA) is an inhibitor of pyruvate dehydrogenase kinase (PDK), which has great promise to realize much more efficient metabolic alterations and improved PDT outcomes. − Red light induced the cleavage of the drug–Ru complex conjugates from MPEG- b -PMCC, which was accompanied by the generation of 1 O 2 , resulting in enhanced therapeutic effects (Figure a). This polymer with direct coordination and photoactivation strategy is more advantageous than the Ru-containing polymer which released Ru complexes and anticancer drugs separately, because the drug was released in this system through breaking the ROS-sensitive linker, which consumed a certain amount of 1 O 2 and reduced the PDT effect . Because of the favorable degradability and biocompatibility of polycarbonate backbones, facile synthesis via direct Ru–N coordination reaction, amplified phototherapy efficiency via combined treatment modalities, and enhanced tissue penetration depth via red light irradiation, poly­(DCARu) presents an attractive option for in vivo phototherapy (Figure b).…”