کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5433393 | 1508987 | 2017 | 11 صفحه PDF | دانلود رایگان |
The abnormal tumor microenvironment (TME) featured with hypoxia, acidosis, dense extracellular matrix and increased 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 chemotherapeutic drug, paclitaxel (PTX), to induce co-assembly of catalase and human serum albumin (HSA), the latter of which is pre-modified with chlorine e6 (Ce6), forming smart multifunctional HSA-Ce6-Cat-PTX nanoparticles via a rather 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 maintain large initial sizes (~Â 100Â nm) during blood circulation and transform into small protein-drug complexes (<Â 20Â nm) within the tumor. Meanwhile, catalase within those nanoparticles could trigger decomposition of endogenic 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-tumor effect in the combined photodynamic/chemotherapy with HSA-Ce6-Cat-PTX. Thus, our work presents a simple drug-induced self-assembly strategy to fabricate enzyme-loaded therapeutic albumin nanoparticles for synergistic cancer combination therapy.
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Journal: Journal of Controlled Release - Volume 263, 10 October 2017, Pages 79-89