Novel Nanotherapeutics for Cancer Immunotherapy by PD-L1-Aptamer-Functionalized and Fexofenadine-Loaded Albumin Nanoparticles

Author:

Lai Xialian1,Yao Fengjiao1,An Yacong1,Li Xundou1,Yang Xian-Da1

Affiliation:

1. Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China

Abstract

Immune checkpoint blockade (ICB) is an important strategy for cancer treatment and has achieved remarkable clinical results. Further enhancement of the efficacy of ICB therapy with a new technical approach is of potential medical importance. In this study, we constructed a novel nanotherapeutic agent (PDL1-NP-FEXO) for cancer immunotherapy by attaching PD-L1 aptamers to albumin nanoparticles that were loaded with H1-antihitamine fexofenadine (FEXO). FEXO has been reported to enhance the immunotherapy response by reducing the immunosuppressive M2-like macrophages in the tumor microenvironment. The albumin nanoparticle was fabricated using a self-assembly method. A dynamic light scattering (DLS) study revealed that the average size of PD-L1 aptamer-modified nanoparticle without FEXO (PDL1-NP) was 135.5 nm, while that of PDL1-NP-FEXO was 154.6 nm. Similar to free PD-L1 aptamer, PDL1-NP could also bind with PD-L1-expressing tumor cells (MDA-MB-231). Of note, compared with free PD-L1 aptamer, PDL1-NP significantly boosted tumor inhibition in CT26-bearing mice. Moreover, PDL1-NP-FEXO further enhanced the antitumor efficacy vs. PDL1-NP in an animal model, without raising systemic toxicity. These results indicate that PDL1-NP-FEXO represents a promising strategy to improve ICB efficacy and may have application potential in cancer immunotherapy.

Funder

Chinese Ministry of Science and Technology

Publisher

MDPI AG

Subject

Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science

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