Multifunctional Microparticles Incorporating Gold Compound Inhibit Human Lung Cancer Xenograft

Abstract

Purpose

Gold porphyrin (AuP) is a complex that has been shown to be potent against various tumors. A biocompatible interpenetrating network (IPN) system comprised of polyethyleneglycol diacrylate (PEGdA) and chemically-modified gelatin has been shown to be an effective implantable drug depot to deliver AuP locally. Here we designed IPN microparticles complexed with AuP to facilitate intravenous administration and to diminish systemic toxicity.

Methods

We have synthesized and optimized an IPN microparticle formulation complexed with AuP. Tumor cell cytotoxicity, antitumor activity, and survival rate in lung cancer bearing nude mice were analyzed.

Results

IPN microparticles maintained AuP bioactivity against lung cancer cells (NCI-H460). In vivo study showed no observable systemic toxicity in nude mice bearing NCI-H460 xenografts after intravenous injection of 6 mg/kg AuP formulated with IPN microparticles. An anti-tumor activity level comparable to free AuP was maintained. Mice treated with 6 mg/kg AuP in IPN microparticles showed 100% survival rate while the survival rate of mice treated with free AuP was much less. Furthermore, microparticle-formulated AuP significantly reduced the intratumoral microvasculature when compared with the control.

Conclusion

AuP in IPN microparticles can reduce the systemic toxicity of AuP without compromising its antitumor activity. This work highlighted the potential application of AuP in IPN microparticles for anticancer chemotherapy.

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Acknowledgements and Disclosures

The authors thank Dr. Regina Lo of Department of Pathology for histological analysis. The authors also thank Zhifeng Zhang for the synthesis of IPN and Ka Chung Tong for the preparation of gold porphyrin. This research was supported by Innovation and Technology Fund (ITS/130/14FP) and HKU Faculty Grant (WJK).

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Correspondence to Chi-Ming Che or Weiyuan John Kao.

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Lee, P.Y., Lok, CN., Che, CM. et al. Multifunctional Microparticles Incorporating Gold Compound Inhibit Human Lung Cancer Xenograft. Pharm Res 37, 220 (2020). https://doi.org/10.1007/s11095-020-02931-8

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KEY WORDS

  • drug delivery
  • drug formulation
  • gold porphyrin
  • interpenetrating network system
  • lung cancer