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

Abstract

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.

Keywords

• immunotherapy
• pd-l1
• tumor vasculature
• dual targeting
• anti-glioma