Bioactive lipid-nanoparticles with inherent self-therapeutic and anti-angiogenic properties for cancer therapy

Angiogenesis inhibition has become a promising therapeutical strategy for cancer treatment. Current clin-ical anti-angiogenesis treatment includes antibodies against vascular endothelial growth factor (VEGF) or VEGF receptor, fusion proteins with high affinity to VEGF receptor, and tyrosine kinase inhibitors of VEGF receptor. However, current treatments are prone to systemic toxicity or acquiring drug resistance. A nat-ural bioactive lipid 1,2-dipalmitoyl-sn-glycero-3-phosphate (dipalmitoyl phosphatidic acid, DPPA) was re-ported to exhibit anti-angiogenic and anti-tumoral activity. However, the hydrophobic property of DPPA largely restricted its clinical use, while systemic infusion of free DPPA could result in undesirable side effects. Herein, we successfully developed DPPA-based lipid-nanoparticles (DPPA-LNPs) which turns the therapeutic payload into nanocarrier. This strategy could improve on DPPA's hydrophiliciy, thereby fa-cilitating its systemic administration. . DPPA-LNPs not only retained the therapeutic anti-angiogenic and anti-tumoral bioactivity of parental DPPA, but also greatly improved its tumor targeting ability via en-hanced permeability and retention (EPR) effect. This strategy not only eliminates the limitation of drug encapsulation rate, toxicity of the delivery vehicle; but also enhances DPPA bioacvtity in vitro and in vivo. Systemic administration of DPPA-LNPs significantly suppressed the blood vessel formation and tu-mor growth of triple negative breast cancer and liver cancer growth on both xenograft tumor models.Statement of significance This is the first-in-kind self-therapeutic inherent lipid to be made into a nanocarrier, with inherent anti-angiogenic and anti-tumor properties. DPPA nanocarrier is fully natural, fully compatible with min-imal systemic toxicity. DPPA nanocarrier can accumulate at high concentration at tumor via EPR effect, exerting both anti-angiogenic and anti-tumor effects in vivo. DPPA nanocarrier could be used to encapsu-late biologics or small molecules for synergistic anti-cancer therapy.(c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automated summary

Inhibition of angiogenesis is a promising strategy for cancer treatment. Current clinical anti-angiogenesis therapies have limitations such as systemic toxicity and drug resistance. By developing DPPA-based lipid-nanoparticles (DPPA-LNPs), the hydrophobicity of DPPA was improved, enabling its systemic administration and enhancing its anti-angiogenic and anti-tumoral effects. DPPA-LNPs significantly suppressed blood vessel formation and tumor growth, making it a potential therapeutic option for breast cancer and liver cancer.