Inhibitor-Decorated Nanoscale Semiconducting Polymer Prodrugs for Photodynamically Amplified Chemotherapy and Metastasis Inhibition

Although photodynamic therapy (PDT) can be adopted for treating malignant tumors, the therapeutic outcome is dissatisfactory due to the hypoxia state of solid tumors and tumor metastasis after treatment. To conquer these issues, the preparation of nanoscale semiconducting polymer prodrugs with decoration of a metastasis inhibitor for photodynamic-amplified chemotherapy and metastasis inhibition is reported. The inhibitor-decorated semiconducting polymer nanoprodrugs (SPNST) are formed through nanoprecipitation of a semiconducting polymer, metastasis inhibitor (SIS3), and hypoxia-responsive prodrug (tirapazamine, TPZ) in the presence of a singlet oxygen (1O2)-cleavable amphiphilic polymer. In the tumor sites with accumulation of nanoparticles, SPNST produce 1O2 via PDT effect under near-infrared (NIR) laser irradiation, leading to apoptosis of partial tumor cells and destruction of 1O2-cleavable amphiphilic polymers for light-activated release of SIS3 and TPZ. The hypoxia of tumors is aggravated due to oxygen consumption during PDT, triggering the activation of TPZ into a toxic form for chemotherapy, which results in photodynamic-amplified chemotherapy. Moreover, the released SIS3 can inhibit the metastasis of tumor cells into lungs. As a result, SPNST exhibit an enhanced efficacy for treating subcutaneous 4T1 tumors and suppressing lung metastasis. Thus, this study reports an NIR photoresponsive drug delivery nanosystem for simultaneous effective treatment of hypoxic tumor and metastasis inhibition.