Novel nanotherapeutics for cancer immunotherapy by albumin nanoparticles functionalized with PD-1 and PD-L1 aptamers

• Published in: Cancer nanotechnology Vol. 15; no. 1; pp. 3 - 16
• Main Authors: Jiang, Qiping, Yao, Fengjiao, An, Yacong, Lai, Xialian, Li, Xundou, Yu, Zhen, Yang, Xian-Da
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.12.2024; Springer Nature B.V; BMC
• Subjects: Albumin; Albumins; Anticancer properties; Aptamers; Bioaccumulation; Biochemistry; Biocompatibility; Biomedical Engineering and Bioengineering; Cancer Research; Chemistry and Materials Science; Colorectal cancer; Effectiveness; Immunotherapy; Lymphocytes; Materials Science; Nanoparticles; Nanotechnology; New technology; PD-1; PD-L1; Toxicity; Nanoparticles; Colon cancer; Immune checkpoint blockade; Immunotherapy; Bispecific; Aptamers; Albumin; PD-L1; PD-1
• ISSN: 1868-6958; 1868-6966
• DOI: 10.1186/s12645-023-00239-x

Background PD-1/PD-L1 blockade plays a crucial role in cancer immunotherapy. Exploration of new technologies to further enhance the efficacy of PD-1/PD-L1 blockade is therefore of potential medical importance. Nanotherapeutics can accumulate in tumor tissues due to enhanced permeability and retention (EPR) effects. In this study, a novel nanotherapeutic for cancer immunotherapy was implemented with albumin nanoparticles functionalized by both PD-1 and PD-L1 aptamers. Results Albumin nanoparticles (NP) were functionalized with either PD-1 aptamers (PD1-NP), PD-L1 aptamers (PDL1-NP), or both types of aptamers (PD1-NP-PDL1). Average sizes of PD1-NP, PDL1-NP, and PD1-NP-PDL1 were 141.8 nm, 141.8 nm, and 164.2 nm, respectively. PD1-NP had good affinity for activated T cells that expresses PD-1. Similarly, PDL1-NP could bind with MDA-MB-231 or CT26 tumor cells that express PD-L1. Moreover, the bispecific PD1-NP-PDL1 could bind with both the activated T cells and the PD-L1-expressing tumor cells, and tether the two type of cells together. Functionally, aptamer-modified nanoparticles exhibited stronger immune-stimulating effects vs. free aptamers. Specifically, PD1-NP or PDL1-NP induced stronger lymphocyte-mediated cytotoxicity against PD-L1-expressing tumor cells in vitro vs. free PD-1 or PD-L1 aptamers. Animal studies also showed that PD1-NP or PDL1-NP significantly improved antitumor efficacy against CT26 colon cancer in vivo vs. free PD-1 or PD-L1 aptamers. Importantly, the bispecific PD1-NP-PDL1 further boosted the in vivo antitumor efficacy compared with PD1-NP or PDL1-NP, without raising systemic toxicity. Conclusion The results suggest that the bispecific PD1-NP-PDL1 is a promising nanotherapeutic to improve the efficacy of PD-1/PD-L1 blockade, and may have application potential in colon cancer treatment.