Biodegradable Hollow Mesoporous Silica Nanoparticles for Regulating Tumor Microenvironment and Enhancing Antitumor Efficiency

Theranostics. 2017 Jul 23;7(13):3276-3292. doi: 10.7150/thno.19987. eCollection 2017.

Abstract

There is accumulating evidence that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Herein, to remodel tumor immune microenvironment and elicit synergistic antitumor effects, lipid-coated biodegradable hollow mesoporous silica nanoparticle (dHMLB) was constructed with co-encapsulation of all-trans retinoic acid (ATRA), doxorubicin (DOX) and interleukin-2 (IL-2) for chemo-immunotherapy. The nanoparticle-mediated combinational therapy provided a benign regulation on tumor microenvironment through activation of tumor infiltrating T lymphocytes and natural killer cells, promotion of cytokines secretion of IFN-γ and IL-12, and down-regulation of immunosuppressive myeloid-derived suppressor cells, cytokine IL-10 and TGF-β. ATRA/DOX/IL-2 co-loaded dHMLB demonstrated significant tumor growth and metastasis inhibition, and also exhibited favorable biodegradability and safety. This nanoplatform has great potential in developing a feasible strategy to remodel tumor immune microenvironment and achieve enhanced antitumor effect.

Keywords: cancer treatment.; drug delivery; immunosuppression; nanoparticles; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Biocompatible Materials / chemistry*
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Drug Liberation
  • Humans
  • Immunity / drug effects
  • Interleukin-2 / metabolism
  • Lipid Bilayers / chemistry
  • Melanoma, Experimental / drug therapy
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / pathology
  • Mice, Inbred C57BL
  • Myeloid-Derived Suppressor Cells / metabolism
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Neoplasm Metastasis
  • Porosity
  • Silicon Dioxide / chemistry*
  • Tissue Distribution / drug effects
  • Tumor Microenvironment / drug effects*

Substances

  • Antineoplastic Agents
  • Biocompatible Materials
  • Cytokines
  • Interleukin-2
  • Lipid Bilayers
  • Silicon Dioxide
  • Doxorubicin