| 单位： 摘要： | Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materialsand Devices, Soochow University, Suzhou, Jiangsu 215123, China The abnormal tumor microenvironment (TME) featured with hypoxia, acidosis, dense extracellular matrix andincreased tumor interstitial fluid pressure is closely related with the resistance of tumors to various therapies.Herein, a unique type of biocompatible nanoscale delivery system is fabricated by utilizing a chemotherapeuticdrug, paclitaxel (PTX), to induce co-assembly of catalase and human serum albumin (HSA), the latter of whichis pre-modified with chlorine e6 (Ce6), forming smart multifunctional HSA-Ce6-Cat-PTX nanoparticles via arather simple one-step method. Upon intravenous injection, HSA-Ce6-Cat-PTX nanoparticles show high tumor accumulation and efficient intra-tumoral diffusion, likely owning to their changeable sizes that can maintainlarge initial sizes (~100 nm) during blood circulation and transform into small protein-drug complexes(<20 nm) within the tumor. Meanwhile, catalase within those nanoparticles could trigger decomposition ofendogenic TME H2O2 to generate oxygen in-situ so as to relieve tumor hypoxia. This effect together with PTX-induced intra-tumoral perfusion enhancement is able to dramatically modulate TME to favor the anti-tumoreffect in the combined photodynamic/chemotherapy with HSA-Ce6-Cat-PTX. Thus, our work presents a simpledrug-induced self-assembly strategy to fabricate enzyme-loaded therapeutic albumin nanoparticles for synergisticcancer combination therapy. |
