PD-1/PD-L1 pathway and angiogenesis dual recognizable nanoparticles for enhancing chemotherapy of malignant cancer

Drug Delivery

Huanglong Qin¹  Hao Li¹  Linsheng Huang¹  Xiao Qu¹  Cheng Kong¹  Xuebing Yan¹  Zhenliang Sun²  Wei Xu³  Yang Zhang⁴  Xufeng Wang⁵  Lin Liang⁶  Man Wang⁶  Duo Cao⁷ 

[1]Department of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

[2]Department of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

[3]Shanghai University of Medicine and Health Sciences Affiliated Sixth People’s Hospital South Campus, Shanghai, China

[4]Department of Orthopaedic, Tong Ren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Chin

[5]Department of Pharmacy, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

[6]Haiwan Community Health Center, Shanghai, China

[7]Shanghai University of Medicine and Health Sciences Affiliated Sixth People’s Hospital South Campus, Shanghai, China

[8]The College of Life Sciences, Northwest University, Xi’an, China

关键词: Immunotherapy;    PD-L1;    tumor vasculature;    dual targeting;    anti-glioma;   

DOI  :  10.1080/10717544.2018.1509907

来源: publisher

【 摘 要 】

Although the cancer immunotherapy represents one of the most promising strategies for cancer treatment, the PD-1/PD-L1 pathway, which involves a receptor-ligand interaction, can induced immunosuppression by disabling tumor-infiltrating lymphocytes (TILs). In the present study, we coupled a PD-L1 (Programmed cell death 1 ligand 1) recognizable peptide DPPA-1 to the sequence of CGKRK, a namely tumor vasculature affinity peptide, to form a new molecule CD peptide. Thereafter, the paclitaxel (PTX)-loaded PCL nanoparticles were developed and modified with the above newly synthesized CD molecules for tumor cells and angiogenesis dual targeting drug delivery. Results of cellular experiments showed that the prepared nanoparticles have a high affinity to both tumor vasculature endothelial cells and tumor cells, which leads to an improved cytotoxicity to cancer cells and inhibition for angiogenesis. In addition, results of in vivo imaging assay exhibited a super tumor targeting efficacy for the CD peptide decorated nanoplatforms. Finally, the pharmacodynamic evaluation was performed and results shown that the tumor-bearing mice treated with CD-NP-PTX achieved the longest medium survival time when compared with others. Simultaneously, different nanoparticles un-loaded with drugs were also subjected to anti-tumor effect studies. Results demonstrated that the mice administrated with D-NP displayed a significantly higher ability of tumor growth inhibition when compared with the NP or C-NP, indicating a super blocking effect of PD-1/PD-L1 pathway for the DPPA-1 peptide. Collectively, these results indicated that the fabricated CD-NP-PTX holds great potential in improving the tumor-targeting drug delivery efficacy and anti-glioma effect.

【 授权许可】

CC BY