Nano-palladium is a cellular catalyst for in vivo chemistry

被引:232
作者
Miller, Miles A. [1 ]
Askevold, Bjorn [1 ]
Mikula, Hannes [1 ]
Kohler, Rainer H. [1 ]
Pirovich, David [1 ]
Weissleder, Ralph [1 ,2 ]
机构
[1] Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA
[2] Harvard Med Sch, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA
来源
NATURE COMMUNICATIONS | 2017年 / 8卷
基金
美国国家卫生研究院;
关键词
POLYMERIC NANOPARTICLES; INTRAVITAL MICROSCOPY; DRUG-DELIVERY; DNA-DAMAGE; CANCER; COMPLEXES; DOXORUBICIN; CELLS; THERAPY; PRODRUG;
D O I
10.1038/ncomms15906
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Palladium catalysts have been widely adopted for organic synthesis and diverse industrial applications given their efficacy and safety, yet their biological in vivo use has been limited to date. Here we show that nanoencapsulated palladium is an effective means to target and treat disease through in vivo catalysis. Palladium nanoparticles (Pd-NPs) were created by screening different Pd compounds and then encapsulating bis[tri(2-furyl) phosphine] palladium(II) dichloride in a biocompatible poly(lactic-co-glycolic acid)-b-polyethyleneglycol platform. Using mouse models of cancer, the NPs efficiently accumulated in tumours, where the Pd-NP activated different model prodrugs. Longitudinal studies confirmed that prodrug activation by Pd-NP inhibits tumour growth, extends survival in tumour-bearing mice and mitigates toxicity compared to standard doxorubicin formulations. Thus, here we demonstrate safe and efficacious in vivo catalytic activity of a Pd compound in mammals.
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页数:13
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共 62 条
  • [1] Preclinical intravital microscopy of the tumour-stroma interface: invasion, metastasis, and therapy response
    Alexander, Stephanie
    Weigelin, Bettina
    Winkler, Frank
    Friedl, Peter
    [J]. CURRENT OPINION IN CELL BIOLOGY, 2013, 25 (05) : 659 - 671
  • [2] Factors affecting the clearance and biodistribution of polymeric nanoparticles
    Alexis, Frank
    Pridgen, Eric
    Molnar, Linda K.
    Farokhzad, Omid C.
    [J]. MOLECULAR PHARMACEUTICS, 2008, 5 (04) : 505 - 515
  • [3] Comparative reactivity of palladium(0) complexes generated in situ in mixtures of triphenylphosphine or tri-2-furylphosphine and Pd(dba)2
    Amatore, C
    Jutand, A
    Meyer, G
    Atmani, H
    Khalil, F
    Chahdi, FO
    [J]. ORGANOMETALLICS, 1998, 17 (14) : 2958 - 2964
  • [4] [Anonymous], 2007, DOXIL R PACK INS
  • [5] Biodistribution properties of nanoparticles based on mixtures of PLGA with PLGA-PEG diblock copolymers
    Beletsi, A
    Panagi, Z
    Avgoustakis, K
    [J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2005, 298 (01) : 233 - 241
  • [6] BERGSTEN P, 1990, J BIOL CHEM, V265, P2584
  • [7] Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology
    Bertrand, Nicolas
    Wu, Jun
    Xu, Xiaoyang
    Kamaly, Nazila
    Farokhzad, Omid C.
    [J]. ADVANCED DRUG DELIVERY REVIEWS, 2014, 66 : 2 - 25
  • [8] The power and potential of doxorubicin-DNA adducts
    Cutts, SM
    Nudelman, A
    Rephaeli, A
    Phillips, DR
    [J]. IUBMB LIFE, 2005, 57 (02) : 73 - 81
  • [9] Bio-palladium: from metal recovery to catalytic applications
    De Corte, Simon
    Hennebel, Tom
    De Gusseme, Bart
    Verstraete, Willy
    Boon, Nico
    [J]. MICROBIAL BIOTECHNOLOGY, 2012, 5 (01): : 5 - 17
  • [10] Biocompatible Copper(I) Catalysts for in Vivo Imaging of Glycans
    del Amo, David Soriano
    Wang, Wei
    Jiang, Hao
    Besanceney, Christen
    Yan, Amy C.
    Levy, Matthew
    Liu, Yi
    Marlow, Florence L.
    Wu, Peng
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2010, 132 (47) : 16893 - 16899