Prodrug-designed nanocarrier co-delivering chemotherapeutic and vascular disrupting agents with exceptionally high...

Chemotherapy remains a vital component of cancer treatment, with combination therapy widely used in clinical practice to overcome the limitations of single-drug administration. However, challenges persist including pharmacokinetic discrepancies among different pharmaceutical agents, and insufficient synergistic efficiency in small-molecule drug combinations. There is an urgent need to develop more efficient combination therapy strategies. Nanocarriers have been extensively used to address issues associated with free drugs, but achieving high delivery efficiency of small-molecular pharmaceuticals through traditional drug delivery methods remains difficult. Herein, we report an exceptionally efficient drug delivery strategy mediated by prodrug design. A prodrug composed of paclitaxel (PTX) and combretastatin A-4 (CA4) was developed to achieve synchronous and efficient delivery of both drugs. When the prodrug was encapsulated by a nanocarrier, the drug loading capacity (DLC) could reach as high as 99 %, almost achieving quantitative drug loading. The good biocompatibility and potent anti-tumor efficacy of the prodrug-loaded nanoparticles were confirmed through both in vitro and in vivo experiments. Our work provides valuable insights into the safe and efficient combination cancer therapy.