Multifunctional Microparticles Incorporating Gold Compound Inhibit Human Lung Cancer Xenograft
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RESEARCH PAPER
Multifunctional Microparticles Incorporating Gold Compound Inhibit Human Lung Cancer Xenograft Pui -Yan Lee 1 & Chun-Nam Lok 1 & Chi-Ming Che 1,2 & Weiyuan John Kao 2,3,4
Received: 8 July 2020 / Accepted: 17 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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 NCIH460 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
* Chi-Ming Che [email protected] * Weiyuan John Kao [email protected] 1
Laboratory for Synthetic Chemistry and Chemical Biology and State Key Laboratory of Synthetic Chemistry, Health at InnoHK, Hong Kong, Hong Kong
2
Department of Chemistry, The University of Hong Kong, Pokfulam, Hong Kong
3
Departments of Industrial and Manufacturing Systems Engineering and Biomedical Engineering, The University of Hong Kong, Pokfulam, Hong Kong
4
Li Ka Shing, Faculty of Medicine, Pokfulam, Hong Kong
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.
KEY WORDS drug delivery . drug formulation . gold porphyrin . interpenetrating network system . lung cancer
INTRODUCTION Cancer is the leading cause of death globally according to the World Health Organization and lung cancer is the most common cause of cancer-associated mortality (1). Tremendous efforts have been focused on the design of drug delivery strategy to facilitate the efficacy of promising cancer therapeutics. Microstructured or nanostructured delivery systems have provided a new opportunity for potent anti-cancer compounds. For example, a biodegradable algae-based system has enabled the lung-targeting delivery of drug in metastasized breast cancer (2). Modified lipophilic nanoparticles have been shown to enhance the delivery into tumor (3). Lipid
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