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Developing a Palladium(II) Agent to Overcome Multidrug Resistance and Metastasis of Liver Tumor by Targeted

Ming Jiang1, Wenjuan Li1, Jinzhe Liang2

  • 1State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources/Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, Guangxi 541004, PR China.

Journal of Medicinal Chemistry
|September 6, 2024
PubMed

Insights

This study developed a palladium (Pd) agent complexed with human serum albumin (HSA) to combat multidrug resistance (MDR) and metastasis in liver tumors. The novel HSA-Pd agent effectively inhibited tumor growth and spread by targeting cancer cells and modulating the tumor microenvironment.

Area of Science:

  • Biomedical Engineering
  • Materials Science
  • Oncology

Background:

  • Multidrug resistance (MDR) and metastasis pose significant challenges in liver tumor treatment.
  • Developing novel therapeutic agents that can overcome these challenges is crucial for improving patient outcomes.

Purpose of the Study:

  • To develop a palladium (Pd) agent based on human serum albumin (HSA) for multiacting on liver tumors.
  • To investigate the efficacy of the HSA-Pd complex in overcoming MDR and metastasis.
  • To elucidate the mechanisms underlying the therapeutic effects of the HSA-Pd complex.

Main Methods:

  • Optimization of Pd(II) 2-acetylpyridine thiosemicarbazone compounds to identify a potent agent (5b).
  • Construction and characterization of a human serum albumin-5b (HSA-5b) complex delivery system.
  • In vivo evaluation of the HSA-5b complex for inhibiting liver tumor growth and metastasis.

Main Results:

  • A Pd(II) compound (5b) demonstrated significant cytotoxicity against multidrug resistant liver cancer cells (HepG2/ADM).
  • The HSA-5b complex effectively inhibited the growth and metastasis of multidrug resistant liver tumors in vivo.
  • HSA conjugation enhanced the targeting of 5b and reduced its systemic side effects.

Conclusions:

  • The HSA-5b complex represents a promising strategy for overcoming MDR and metastasis in liver tumors.
  • The therapeutic efficacy involves multiaction on cancer cells, immune response activation, and inactivation of cancer-associated fibroblasts.
  • This approach offers a potential new avenue for liver cancer therapy.

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