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Blood-triggered generation of platinum nanoparticle functions as an anti-cancer agent.

ABSTRACT: Since the discovery of metal nanoparticles (NPs) in the 1960s, unknown toxicity, cost and the ethical hurdles of research in humans have hindered the translation of these NPs to clinical use. In this work, we demonstrate that Pt NPs with protein coronas are generated in vivo in human blood when a patient is treated with cisplatin. These self-assembled Pt NPs form rapidly, accumulate in tumors, and remain in the body for an extended period of time. Additionally, the Pt NPs are safe for use in humans and can act as anti-cancer agents to inhibit chemotherapy-resistant tumor growth by consuming intracellular glutathione and activating apoptosis. The tumor inhibitory activity is greatly amplified when the Pt NPs are loaded in vitro with the chemotherapeutic drug, daunorubicin, and the formulation is effective even in daunorubicin-resistant models. These in vivo-generated metal NPs represent a biocompatible drug delivery platform for chemotherapy resistant tumor treatment.

SUBMITTER: Zeng X

PROVIDER: S-EPMC6987201 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Blood-triggered generation of platinum nanoparticle functions as an anti-cancer agent.

Zeng Xin X Sun Jie J Li Suping S Shi Jiyun J Gao Han H Sun Leong Wei W Wu Yiqi Y Li Minghui M Liu Chengxin C Li Ping P Kong Jing J Wu Yi-Zhou YZ Nie Guangjun G Fu Yuming Y Zhang Gen G

Nature communications 20200128 1

Since the discovery of metal nanoparticles (NPs) in the 1960s, unknown toxicity, cost and the ethical hurdles of research in humans have hindered the translation of these NPs to clinical use. In this work, we demonstrate that Pt NPs with protein coronas are generated in vivo in human blood when a patient is treated with cisplatin. These self-assembled Pt NPs form rapidly, accumulate in tumors, and remain in the body for an extended period of time. Additionally, the Pt NPs are safe for use in hum ...[more]

PMID: 31992692

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Project description:Metal nanoparticles and the combination of metal nanoparticles with graphene oxide are widely used in environmental, agriculture, textile, and therapeutic applications. The effect of graphene oxide-green platinum nanoparticles (GO-PtNPs) on human prostate cancer cells (LNCaP) is unclear. Therefore, this study aimed to synthesize a nanocomposite of GO-PtNPs and evaluate their effect on prostate cancer cells. Herein, we synthesized GO-PtNPs using vanillin and characterized GO-PtNPs. GO-PtNP cytotoxicity in LNCaP cells was demonstrated by measuring cell viability and proliferation. Both decreased in a dose-dependent manner compared to that by GO or PtNPs alone. GO-PtNP cytotoxicity was confirmed by increased lactate dehydrogenase release and membrane integrity loss. Oxidative stress induced by GO-PtNPs increased malondialdehyde, nitric oxide, and protein carbonyl contents. The effective reactive oxygen species generation impaired the cellular redox balance and eventually impaired mitochondria by decreasing the membrane potential and ATP level. The cytotoxicity to LNCaP cells was correlated with increased expression of proapoptotic genes (p53, p21, Bax, Bak, caspase 9, and caspase 3) and decreased levels of antiapoptotic genes (Bcl2 and Bcl-xl). Activation of the key regulators p53 and p21 inhibited the cyclin-dependent kinases Cdk2 and Cdk4, suggesting that p53 and p21 activation in GO-PtNP-treated cells caused genotoxic stress and apoptosis. The increased expression of genes involved in cell cycle arrest and DNA damage and repair, and increased levels of 8-oxo-deoxyguanosine and 8-oxoguanine suggested that GO-PtNPs potentially induce oxidative damage to DNA. Thus, GO-PtNPs are both cytotoxic and genotoxic. LNCaP cells appear to be more susceptible to GO-PtNPs than to GO or PtNPs. Therefore, GO-PtNPs have potential as an alternate and effective cancer therapeutic agent. Finally, this work shows that the combination of graphene oxide with platinum nanoparticles opens new perspectives in cancer therapy. However further detailed mechanistic studies are required to elucidate the molecular mechanism of GO-PtNPs induced cytotoxicity in prostate cancer.

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Blood-triggered generation of platinum nanoparticle functions as an anti-cancer agent.

Publications

Blood-triggered generation of platinum nanoparticle functions as an anti-cancer agent.

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