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Evaluation of a Platinum–Acridine Anticancer Agent and Its Liposomal Formulation in an in vivo Model of Lung Adenocarcinoma
Author(s) -
Ding Song,
Hackett Christopher L.,
Liu Fang,
Hackett Ryan G.,
Bierbach Ulrich
Publication year - 2021
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000637
Subject(s) - liposome , cisplatin , in vivo , chemistry , pharmacology , acridine , cytotoxicity , phosphatidylcholine , polyethylene glycol , doxorubicin , cancer research , biochemistry , biophysics , chemotherapy , medicine , in vitro , membrane , biology , phospholipid , organic chemistry , microbiology and biotechnology
Liposomal formulations have been developed for a highly cytotoxic platinum–acridine agent, [PtCl(pn)(C 18 H 21 N 4 )](NO 3 ) 2 (PA, pn=propane‐1,3‐diamine), and fully characterized. Nanoliposomes consisting of hydrogenated soybean phosphatidylcholine (HSPC), 1,2‐dihexadecanoyl‐sn‐glycero‐3‐phospho‐(1'‐rac‐glycerol) (DPPG), and polyethylene glycol‐2000‐distearoylphosphatidylethanolamine (DSPE‐mPEG 2k ) were able to stably encapsulate PA at payload‐to‐lipid ratios of 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 in cultured lung cancer cells. Unencapsulated PA and one of the newly designed liposomal formulations show promising tumor growth inhibition in tumor xenografts derived from A549 lung adenocarcinoma cells of 76 % and 72 %, respectively. Cisplatin showed no significant efficacy at a 10‐fold higher dose. These findings underscore the utility of platinum‐acridine agents for treating aggressive, chemoresistant forms of cancer and validate nanoliposomes as a biocompatible, expandable platform for their intravenous delivery and other potential routes of administration.