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

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.

Different Targeting Ligands-Mediated Drug Delivery Systems for Tumor Therapy

“…This subsection focuses on recent advances and challenges in aptamer-mediated targeted drug delivery systems in cancer therapy. It specifically discusses two main categories: aptamer-drug conjugates (ApDCs) and aptame-conjugated nanoparticles [ 79 , 80 ] ( Figure 4 ).…”

Engineered biological nanoparticles as nanotherapeutics for tumor immunomodulation

“…The PDL1-NP-FEXO bind to PD-L1 positive MDA-MB-231 cells in vitro and significantly inhibited CT26 tumor growth in vivo without generating systemic toxicity. 287 A similar formulation was fabricated by Yao et al with CTLA-4 aptamers (CTLA-4-NP-FEXO) which could bind CTLA-4 positive cells and improved antitumor immunity in vivo via lymphocyte activation. 288 Combination therapy was explored with HSA-PTX generated via albumin bound technology and then pooled with anti-PD-L1 monoclonal antibody through a pH-sensitive linker (Fig.…”

Recent Advancements of Aptamers in Cancer Therapy

“…Several such fluorescence aptasensors were successfully combined with photodynamic therapy, photothermal therapy, and chemotherapy techniques to diagnose and treat cancers. 26 ■ FUNCTIONALIZED NANOPARTICLES: GOLD,…”

“…This drug was very effective when loaded on self-assembled albumin nanoparticles that were further attached to PD-L1 aptamers (Figure ). This strategy was successfully proven to display enhanced efficacy against ICBs …”