Paclitaxel prodrug nanoparticles boost antitumor efficacy via hitchhiking of human serum albumin

Improving drug delivery efficacy is the key point for enhancing the therapeutic index of medicines. Herein, we report fatty chain conjugated paclitaxel (PTX) prodrugs with a disulfide bond as linker. The formed prodrugs can self-assemble into stable nanoparticles in aqueous solutions, and rapidly transform into long-circulating nanocomplexes via the non-covalent binding to serum albumin in blood, enabling efficient drug delivery and robust antitumor effect. PTX prodrug (PC) with single-chain possess the improved self-assembly and interaction with albumins. The formed PC@albumin nanocomplexes reinforce the responsiveness of prodrug activation, and exhibit the enhanced tumor suppression ability. This strategy of hitchhiking albumin to deliver therapeutic agents holds great promise for enhanced chemotherapy.