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Nat Commun ; 11(1): 567, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992692

RESUMO

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.


Assuntos
Antineoplásicos/sangue , Antineoplásicos/farmacologia , Nanopartículas Metálicas/química , Platina/sangue , Platina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Daunorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Tolerância a Medicamentos , Feminino , Glutationa/metabolismo , Células Hep G2 , Humanos , Células K562 , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Tamanho da Partícula , Coroa de Proteína , Fatores de Tempo , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra
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