ORGS2-0867
Fatty Acid–Integrated Gas-Generating Polymeric Nanoparticles for Enhancing Anti–PD-L1 Therapy in Melanoma
Topic
GS2. Graduate Student Oral Session II: Functional Biomaterials and Cosmetic Polymer Engineering
When and Where
Sep 28, 2026
14:12 - 14:24
Room 102
Session Chairs
Chaenyung CHA
Ilkoo NOH
Jun Shik CHOI
Presenter(s)
In young LEE (Hanyang University)
Co-Author(s)
Abstract
Melanoma is an aggressive skin cancer in which immune checkpoint blockade has improved treatment outcomes, but many tumors show limited or transient responses. Aggressive or drug-resistant cancers often rely on lipid uptake and fatty acid handling for survival, invasion, and adaptation to therapeutic stress. Therefore, we proposed palmitic acid-integrated gas-generating polymeric nanoparticles (PA-gPN) to induce necrotic melanoma cell death and improve the response to anti-PD-L1 therapy. PA-gPN consisted of PLGA, integrated palmitic acid for fatty acid-associated uptake, and calcium carbonate as an acid-responsive CO₂-generating component. In B16-F10 melanoma cells, PA-integrated nanoparticles showed higher cellular uptake than non-modified nanoparticles, and this uptake was reduced by inhibition of FABP and CD36, suggesting the involvement of fatty acid-associated pathways. After intracellular delivery, PA-gPN generated CO2 under acidic endosomal/lysosomal conditions, leading to membrane disruption and necrotic cell death. The treatment also increased the release of DAMPs, including ATP, HSP70, and HMGB1, and promoted macrophage-mediated phagocytosis of dying melanoma cells. In B16-F10 melanoma-bearing mice, intratumoral injection of PA-gPN combined with systemic anti-PD-L1 antibody suppressed tumor growth more effectively than either treatment alone. The combination reduced tumor weight, prolonged survival, and increased TUNEL-positive tumor cell death and CD8+ T cell infiltration. In a secondary tumor challenge model, the same combination suppressed both primary and secondary tumor growth and enhanced immune activation in tumor-draining lymph nodes, spleen, and tumor tissues. These results suggest that PA-gPN can link fatty acid-associated delivery, gas-generating necrotic cell death, and antitumor immune activation. This polymeric nanoparticle platform may provide a useful strategy for enhancing immune checkpoint blockade in lipid metabolism-active melanoma.
