Complex of cisplatin with biocompatible poly(ethylene glycol) with pendant carboxyl groups for the effective treatment of liver cancer

Abstract

Cisplatin was incorporated into polymeric carriers through the coordination of Pt with the carboxylic groups of methoxypoly(ethylene glycol) (mPEG)-block-poly[(2-carboxy-ethylsulfanyl)-propyl glycidyl ether] (PCPGE). The mPEG-b-PCPGE/Pt complexes with a Pt content of 14 wt % could self-assemble into spheric micelles with diameter of about 80 nm in aqueous solution. The effective internalization of the polymer platinum micelles by the cells via an endocytosis mechanism was confirmed by confocal laser scanning microscopy and flow cytometry. The antitumor activity of the polymeric micelles was similar to that of cisplatin in vitro. The in vivo blood clearance of platinum was studied, and the results show that the micelles exhibited longer blood circulation than the free cisplatin. The biodistribution of cisplatin and its micelles in mice was studied through the measurement of the Pt content in plasma, organs, and tumors, especially in tumor cell DNA. Their antitumor activity in vivo, assessed in mice bearing H22 liver cancers, showed that the micelles exhibited greater antitumor efficacy than free cisplatin. Therefore, this polymer platinum micelle is a promising candidate as a smart antitumor drug carrier for malignancy therapy in future clinical applications.

Enhanced and Selective Antiproliferative Activity of Methotrexate-Functionalized-Nanocapsules to Human Breast Cancer Cells (MCF-7)

“…Nanocarrier drug delivery systems are very promising strategies for the treatment of tumors leading to improved therapeutic efficacy [ 1 , 2 , 3 ] and reduced drug doses [ 4 , 5 ]. The incorporation of drugs into nanocarriers can be performed by either encapsulation or surface functionalization [ 6 , 7 , 8 ]. Drug-loaded nanoparticles accumulate at the target tissues or organs due to diverse factors, such as permeability of barriers, tissue damage and pH environment [ 9 , 10 ].…”

Mitochondria-Localized Fluorescent BODIPY-Platinum Conjugate

“…We also quantified content of Pt in mtDNA from BODIPY-Pt and cisplatin. The HeLa cells were incubated with each of them at a concentration of 5 μM for 2 h. Then the collection and purification of the mtDNA was done by using a mitochondrial DNA isolation kit, and the Pt concentration in mtDNA was obtained by ICP-MS. , Agarose gel electrophoresis (Figure S5) demonstrated that the mtDNA (about 16.5 kb) had been isolated from the mitochondria of HeLa cells successfully. As shown in Figure S6, the Pt contents of BODIPY-Pt in the mtDNA are higher than that of cisplatin, which can also give a proof for the mitochondria localization of BODIPY-Pt.…”

Rethinking Alkylating(-Like) Agents for Solid Tumor Management

“…Indeed, DDS have been described to passively target tumor cells through the enhanced permeability and retention effect (EPR)[87,88]. Although controversial, this paradigm has given rise to the development of various DDS, including for vectorization of platinum derivatives [70,[88][89][90][91][92][93]. Interestingly, active targeting can be achieved by functionalizing nanocarriers with various ligands that specifically bind to…”