Apigenin-Loaded PLGA-DMSA Nanoparticles: A Novel Strategy to Treat Melanoma Lung Metastasis

• DOI: 10.1021/acs.molpharmaceut.0c00977
• Publication Date: 2021-03-29T19:32:33Z
• Authors: Ramkrishna Sen; Soumya Ganguly; Shantanu Ganguly; Mita Chatterjee D...; Subrata Chakraborty; Biswajit Mukherjee; Dipankar Chattopa...
• Keywords: Internalization; PLGA

The flavone apigenin (APG), alone as well in combination with other chemotherapeutic agents, is known to exhibit potential anticancer effects various tumors and inhibit growth metastasis of melanoma. However, the nanoparticles (APG-NPs) prevent lung colonization malignant melanoma has not been investigated. APG-loaded PLGA-NPs were surface-functionalized meso-2,3-dimercaptosuccinic acid (DMSA) for treatment metastasis. DMSA-conjugated NPs (DMSA-APG-NPs) administered by an oral route exhibited sustained APG release showed considerable enhancement plasma half-life, Cmax value, bioavailability compared APG-NPs both lungs. comparably higher cellular internalization B16F10 A549 cell lines that plain NPs. Increased cytotoxicity was observed DMSA-APG-NPs cells. This difference between two formulations lower Significant depolarization mitochondrial transmembrane enhanced level caspase activity cells treated well. Western blot analysis proteins performed understand mechanism apoptosis prevention migration invasion. DMSA conjugation substantially increased accumulation given intravenous lungs at 6 8 h. also corroborated scintigraphic imaging studies radiolabeled route. Conjugation allowed comparatively penetration evident from vitro three-dimensional tumor spheroid model study. Finally, therapeutic efficacy formulation established experimental metastases, which suggested improved antitumor antimetastasis following administration.