Biological and Medicinal Chemistry

Evaluation of a Platinum–Acridine Anticancer Agent and Its Liposomal Formulation in an In Vivo Model of Lung Adenocarcinoma



Liposomal formulations have been developed for a highly cytotoxic platinum–acridine hybrid agent, [PtCl(pn)(C18H21N4)](NO3)2 (PA, pn = propane-1,3-diamine), and fully characterized. PEGylated nanoliposomes consisting of hydrogenated soybean phosphatidylcholine (HSPC), anionic 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1´-rac-glycerol) (DPPG), and polyethylene glycol-2000-distearoylphosphatidylethanolamine (DSPE-mPEG2k) were able to stably encapsulate PA at payload-to-lipid ratios ranging from approximately 2–20%. The fusogenic properties of the liposomes promote efficient cellular uptake of PA across the plasma membrane, which results in vesicular transport of payload to the nucleus, as confirmed by confocal fluorescence microscopy in cultured lung cancer cells. Unencapsulated PA and one of the newly designed liposomal formulations show promising efficacy in tumor xenografts derived from A549 cells (human lung adenocarcinoma). The findings underscore the utility of platinum–acridine agents for treating aggressive, chemoresistance cancers and validate nanoliposomes as a biocompatible, expandable platform for their intravenous delivery and other potential routes of administration.


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Supplementary material

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Lipos SI