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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.
Platinum based drugs like cisplatin are common chemotherapy treatments for cancer. Here, the authors report on the in situ formation of platinum nanoparticles in patients and demonstrated how platinum nanoparticles can be synthesized using patients’ blood and provide effective drug delivery and cancer treatments.
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1 Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China (GRID:grid.459791.7) (ISNI:0000 0004 1757 7869); Nanjing Medical University, Department of Cell Biology, School of Basic Medicine, Nanjing, China (GRID:grid.89957.3a) (ISNI:0000 0000 9255 8984)
2 Nanjing Medical University, Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, School of Public Health, Nanjing, China (GRID:grid.89957.3a) (ISNI:0000 0000 9255 8984)
3 CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, China, Beijing, China (GRID:grid.419265.d) (ISNI:0000 0004 1806 6075); University of Chinese Academy of Sciences, Center of Materials Science and Optoelectronics Engineering, Beijing, China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419)
4 Chinese Academy of Sciences, Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Beijing, China (GRID:grid.9227.e) (ISNI:0000000119573309)
5 Beihang University, School of Biological Science and Medical Engineering, Beijing, China (GRID:grid.64939.31) (ISNI:0000 0000 9999 1211)
6 Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, Cambridge, USA (GRID:grid.116068.8) (ISNI:0000 0001 2341 2786)
7 Nanjing Medical University, Department of Cell Biology, School of Basic Medicine, Nanjing, China (GRID:grid.89957.3a) (ISNI:0000 0000 9255 8984)
8 Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China (GRID:grid.459791.7) (ISNI:0000 0004 1757 7869)
9 CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, China, Beijing, China (GRID:grid.419265.d) (ISNI:0000 0004 1806 6075); University of Chinese Academy of Sciences, Center of Materials Science and Optoelectronics Engineering, Beijing, China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419); The University of Queensland, Australian Institute for Bioengineering and Nanotechnology, Brisbane Qld, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537)
10 Beihang University, School of Biological Science and Medical Engineering, Beijing, China (GRID:grid.64939.31) (ISNI:0000 0000 9999 1211); Beihang University, Beijing Advanced Innovation Center for Biomedical Engineering, Beijing, China (GRID:grid.64939.31) (ISNI:0000 0000 9999 1211)