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2000
Volume 25, Issue 19
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

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(e-caprolactone)-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 and .

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

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2025-05-26
2025-10-22

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The Role of Cisplatin Prodrugs Bonded to Polymer Carriers for Nanodrug-targeted Treatment of In situ Hepatocellular Carcinoma
Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) 25, 1564 (2025); https://doi.org/10.2174/0118715206347681250312142125
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  • Article Type:     Research Article
Keyword(s): Cisplatin(IV); hepatocellular carcinoma; HepG2 cells; micelles; MPEG-b-PCL-b-PLL; polymer; western blot

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