The Role of Cisplatin Prodrugs Bonded to Polymer Carriers for Nanodrug-targeted Treatment of In situ Hepatocellular Carcinoma


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Abstract

Background:The toxic effects of cisplatin limit its therapeutic efficacy on hepatocellular carcinoma (HCC). Cisplatin(IV) (Pt(IV)) with better stability needs an effective drug delivery strategy. Here, we explored the toxic and inhibitory effects and cell Pt contents of monomethoxyl poly(ethylene glycol)-block-poly(ecaprolactone)- block-poly(L-lysine) (MPEG-b-PCL-b-PLL)/Pt(IV) micelles (M(P3)) on HCC, and evaluated the therapeutic effect of (M (Pt (IV)) on HCC in vitro and in vivo.

Methods:We successfully constructed HCC model in BALB/c mice and prepared M(P3). The H22 and HepG2 cells were incubated with cisplatin, M(P3), and cisPt(IV)-(COOH)2 at 2, 10, 20, 50, 100 and 250 μM equivalent platinum (Pt) concentrations for 48 h and at 5 μM for 2/6 h. The HCC mice received cisplatin, M(P3), and cisPt(IV)-(COOH)2 (5 mg equivalent Pt/kg, once a week) for five weeks. The cell activity was assessed by MTT assay. The Pt contents were assayed by an inductively coupled plasma mass spectrometer (ICP-MS). The liver tumor weight was measured. The levels of liver tumor hepatorenal function indicators and malignant indicators were estimated by biochemical analysis and Western blot.

Results:The activity of H22 and HepG2 cells: cisPt(IV)-(COOH)2-treated > M(P3)-treated > cisplatin-treated. The Pt contents of H22 and HepG2 cells: M(P3)-treated > cisplatin-treated > cisPt(IV)-(COOH)2-treated cells. The hepatorenal function of HCC mice: M(P3)-treated > cisPt(IV)-(COOH)2-treated > cisplatin-treated. According to the weight and levels of malignant indicators of liver tumor, the therapeutic effect on HCC mice: cisplatintreated > M(P3)-treated > cisPt(IV)-(COOH)2-treated.

Conclusions:Although the inhibitory effect of M(P3) on HCC is not as good as cisplatin, M(P3) has significantly lower hepatorenal toxicity and remarkably higher cell Pt contents.

About the authors

Zhijian Li

Hepatobiliary Surgery Department, The People’s Hospital of Baoan Shenzhen

Email: info@benthamscience.net

Lan Luo

Gastroenterology Department, The People’s Hospital of Baoan Shenzhen

Email: info@benthamscience.net

Zhan Wang

Gastrointestinal Surgery Department, The People’s Hospital of Baoan Shenzhen

Email: info@benthamscience.net

Jie Hou

Gastrointestinal Surgery Department, The People’s Hospital of Baoan Shenzhen

Author for correspondence.
Email: info@benthamscience.net

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