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Tumor associated macrophages and angiogenesis dual-recognizable nanoparticles for enhanced cancer chemotherapy
Authors:Duo Cao  Lin Liang  Yixin Xu  Ji Sun  Meng Lei  Man Wang  Yahui Wei  Zhenliang Sun
Institution:1. The College of Life Sciences, Northwest University, Xi’an, Shaanxi, China;2. Shanghai University of Medicine & Health Sciences Affiliated Sixth People''s Hospital South Campus, Shanghai, China;3. Department of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China;4. School of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai, China;5. Shanghai University of Medicine & Health Sciences, Shanghai, China
Abstract:Tumor-associated macrophages (TAMs) and angiogenesis are increasingly considered as the pivotal factors that affect tumor progress. Herein, we developed the paclitaxel (PTX)-loaded nanoparticles (NP/PTX) and decorated it with an innovative peptide YI (YINP/PTX) for simultaneously targeting delivery of drug to TAMs and angiogenesis. We demonstrated that the modification of YI peptide significantly enhanced the internalization of nanoparticles by cells and accumulation of nanoparticles in tumor tissues, but down regulated the distribution of them in normal tissues especially the liver. We also made a confirmation that the YI peptide decorated nanoparticles had an excellent co-localization with TAMs and angiogenesis in vivo. Finally, in the HT-26 colorectal tumor-bearing mice, a pharmacodynamic evaluation was performed and results showed that the YINP/PTX was more effective than other PTX formulations in anti-tumor growth. These results together suggested that the prepared nanoparticles are promising in targeting delivery of chemotherapeutics to tumor microenvironment for enhancing tumor therapy effect.
Keywords:Tumor microenvironment  Tumor-associated macrophages  Angiogenesis  Nanoparticles  Tumor therapy
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