IR780‐Loaded Hyaluronic Acid@Gossypol–Fe(III)–EGCG Infinite Coordination Polymer Nanoparticles for Highly Efficient Tumor Photothermal/Coordinated Dual Drugs Synergistic Therapy

Abstract A novel strategy called “two‐stage dual‐synergistic tumor therapy (TDTT),” which combines photothermal therapy with infinite coordination polymers (ICPs) chemotherapy at the first stage in the short term and two drugs of ICPs synergistic chemotherapy (coordinated dual drugs chemotherapy) at the second stage in the long term, is proposed. This strategy is achieved by preparing IR780‐loaded hyaluronic acid (HA) encapsulated gossypol–Fe(III)–epigallocatechin gallate (EGCG) ICP nanoparticles (HA@IRGFE ICP NPs), which have IR780 inclusions, a natural gossypol, and EGCG coordinated with Fe 3+ framework, and a HA shell. It is found that the HA@IRGFE ICP NPs’ diameter is 120.0 ± 39.5 nm and has tumor‐targeting ability and can be rapidly released in tumor environment. Their photothermal conversion efficiency is greatly improved to 47.8%, and the total combination index of TDTT is 0.38, which indicates an excellent synergistic therapy result. These HA@IRGFE ICP NPs show low toxicity with a high tolerated dose (30.0 mg kg −1 ), a high tumor inhibition rate of 98.7%, and a very low tumor recurrence rate over 60 days (12.5%) with TDTT strategy, indicating their great potential applications in the field of tumor therapy.