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Development of Facile and Versatile Platinum Drug Delivering Silicasome Nanocarriers for Efficient Pancreatic Cancer Chemo-Immunotherapy.
Liu, Xiangsheng; Jiang, Jinhong; Chang, Chong Hyun; Liao, Yu-Pei; Lodico, Jared J; Tang, Ivanna; Zheng, Emily; Qiu, Waveley; Lin, Matthew; Wang, Xiang; Ji, Ying; Mei, Kuo-Ching; Nel, Andre E; Meng, Huan.
Afiliação
  • Liu X; Division of Nanomedicine, Department of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Jiang J; California NanoSystems Institute, University of California, Los Angeles, CA, 90095, USA.
  • Chang CH; California NanoSystems Institute, University of California, Los Angeles, CA, 90095, USA.
  • Liao YP; California NanoSystems Institute, University of California, Los Angeles, CA, 90095, USA.
  • Lodico JJ; Division of Nanomedicine, Department of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Tang I; California NanoSystems Institute, University of California, Los Angeles, CA, 90095, USA.
  • Zheng E; Department of Physics and Astronomy, University of California, Los Angeles, CA, 90095, USA.
  • Qiu W; Division of Nanomedicine, Department of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Lin M; Division of Nanomedicine, Department of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Wang X; Division of Nanomedicine, Department of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Ji Y; Division of Nanomedicine, Department of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Mei KC; Division of Nanomedicine, Department of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Nel AE; Division of Nanomedicine, Department of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Meng H; Division of Nanomedicine, Department of Medicine, University of California, Los Angeles, CA, 90095, USA.
Small ; 17(14): e2005993, 2021 04.
Article em En | MEDLINE | ID: mdl-33682329
ABSTRACT
In this study a mesoporous silica nanoparticle (MSNP) based platform is developed for high-dose loading of a range of activated platinum (Pt) chemo agents that can be attached to the porous interior through the use of electrostatic and coordination chemistry under weak-basic pH conditions. In addition to the design feature for improving drug delivery, the MSNP can also be encapsulated in a coated lipid bilayer (silicasome), to improve the colloidal stability after intravenous (IV) injection. Improved pharmacokinetics and intratumor delivery of encapsulated activated oxaliplatin (1,2-diamminocyclohexane platinum(II) (DACHPt)) over free drug in an orthotopic Kras-derived pancreatic cancer (PDAC) model is demonstrated. Not only does IV injection of the DACHPt silicasome provide more efficacious cytotoxic tumor cell killing, but can also demonstrate that chemotherapy-induced cell death is accompanied by the features of immunogenic cell death (ICD) as well as a dramatic reduction in bone marrow toxicity. The added ICD features are reflected by calreticulin and high-mobility group box 1 expression, along with increased CD8+ /FoxP3+ T-cell ratios and evidence of perforin and granzyme B release at the tumor site. Subsequent performance of a survival experiment, demonstrates that the DACHPt silicasome generates a significant improvement in survival outcome, which can be extended by delayed administration of the anti-PD-1 antibody.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Preparações Farmacêuticas / Antineoplásicos Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Preparações Farmacêuticas / Antineoplásicos Idioma: En Ano de publicação: 2021 Tipo de documento: Article