Reversal of multidrug resistance in human lung cancer cells by delivery of 3-octadecylcarbamoylacrylic acid–cisplatin-based liposomes

Abstract

Liposome-based drug delivery system would be an innovative and promising candidate to circumvent multidrug resistance (MDR) of cisplatin (CDDP). However, the reversal efficacy of liposomal CDDP was severely impaired by weak cellular uptake and insufficient intracellular drug release. In this study, 3-octadecylcarbamoylacrylic acid–CDDP nanocomplex (OMI–CDDP–N)-based liposomes (OCP-L) with high cellular uptake and sufficient intracellular drug release were designed to circumvent MDR of lung cancer. OMI–CDDP–N was synthesized through a pH-sensitive monocarboxylato and an O→Pt coordinate bond, which is more efficient than CDDP. Also, OCP-L incorporated with OMI–CDDP–N could induce effective cellular uptake, enhanced nuclear distribution, and optimal cellular uptake kinetics. In particular, OCP-L presented superior effects on enhancing cell apoptosis and in vitro cytotoxicity in CDDP-resistant human lung cancer (A549/CDDP) cells. The mechanisms of MDR reversal in A549/CDDP cells by OCP-L could attribute to organic cation transporter 2 restoration, ATPase copper-transporting beta polypeptide suppression, hypoxia-inducible factor 1 α-subunit depletion, and phosphatidylinositol 3-kinase/Akt pathway inhibition. These results demonstrated that OCP-L may provide an effective delivery of CDDP to resistant cells to circumvent MDR and enhance the therapeutic index of the chemotherapy.

Chitosan-based self-assembled nanocarriers coordinated to cisplatin for cancer treatment

“…4 Preparation methods of cisplatin-loaded polymeric carriers have been reported, such as encapsulation, covalent attachment (conjugation), and complexation (co-ordination bound). Recently, drug delivery systems for cisplatin have been developed that utilize polymer-platinum conjugates or prodrugs, 5,6 complexes in nanotubes 7 and micro/nanoparticulates such as liposomes, [8][9][10] nanocomplexes, 3 gold nanoparticles, 11 and polymeric micelles. [12][13][14][15] The complex of cisplatin and poly(ethylene glycol)poly(aspartic acid) block copolymer (PEG-P(Asp)) in an aqueous medium has been reported as a successful system for drug delivery, 12,13 which also reduced nephrotoxicity.…”

Formoxanthone C Inhibits Malignant Tumor Phenotypes of Human A549 Multidrug Resistant-cancer Cells through Signal Transducer and Activator of Transcription 1-Histone Deacetylase 4 Signaling

“…Lung cancer represents the most common malignancy and is responsible for the leading cause of cancer-related mortality and death worldwide [ 1 ]. Unfortunately, the success of chemotherapy is hindered by the development of multidrug resistance (MDR) in cancer.…”