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

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.

Novel nanotherapeutics for cancer immunotherapy by CTLA-4 aptamer-functionalized albumin nanoparticle loaded with antihistamine.

INTRODUCTION: Immune checkpoint blockade (ICB) is a promising strategy for cancer treatment and has generated remarkable clinical results against multiple malignancies. Exploration of new technical approaches to further boost the therapeutic efficacy of ICB is of potential medical importance. In this study, we designed a novel nanotherapeutics for ICB immunotherapy. METHODS: CTLA-4 aptamers were conjugated to the surface of albumin nanoparticle to construct an aptamer-modified nanostructure (Apt-NP). To improve ICB efficacy, fexofenadine (FEXO), an antihistamine, was encapsulated into Apt-NP to make a drug-loaded nanoparticle (Apt-NP-FEXO). The antitumor efficacies of Apt-NP and Apt-NP-FEXO were evaluated in vitro and in vivo. RESULTS: Apt-NP and Apt-NP-FEXO had average diameters of 149 nm and 159 nm, respectively. Similar to free CTLA-4 aptamers, Apt-modified NPs could selectively bind with CTLA-4 positive cells and improve lymphocyte-mediated antitumor cytotoxicity in vitro. In animal studies, compared with free CTLA-4 aptamer, Apt-NP significantly enhanced antitumor immunity. Moreover, Apt-NP-FEXO further improved antitumor efficacy vs. Apt-NP in vivo. CONCLUSION: The results suggest that Apt-NP-FEXO represents a novel strategy to improve ICB outcome and may have application potential in cancer immunotherapy.