Platelet-mimicking nanoparticles co-loaded with W18O49 and metformin alleviate tumor hypoxia for enhanced photodynamic therapy and photothermal therapy

Acta Biomater. 2018 Oct 15:80:296-307. doi: 10.1016/j.actbio.2018.09.017. Epub 2018 Sep 15.

Abstract

W18O49-mediated photodynamic therapy (PDT) and photothermal therapy (PTT) are limited by the easily oxidized property and tumor hypoxia. Here, we report the development of platelet membranes as nanocarriers to co-load W18O49 nanoparticles (NPs) and metformin (PM-W18O49-Met NPs). Platelet membranes can protect W18O49 from oxidation and immune evasion, and increase the accumulation of W18O49 in tumor sites via the passive EPR effect and active adhesion between platelets and cancer cells. The introduction of metformin (Met), a typical anti-diabetic drug, can alleviate the tumor hypoxia through reducing oxygen consumption. As a result, ROS and heat generation are both greatly increased, as revealed by ROS/hypoxia imaging in vitro, IR thermal imaging in vivo and PET imaging in vivo. PM-W18O49-Met NPs show the improved therapeutic effects with greatly inhibited tumor growth and induced tumor cell apoptosis. Therefore, our work provides a novel strategy for simultaneous enhanced PDT and PTT, which is promising in bioapplication. STATEMENTE OF SIGNIFICANCE: W18O49-mediated photodynamic therapy and photothermal therapy are limited by the poor delivery of nanoparticles to tumors, the easily oxidized property, and tumor hypoxia environment, which will induce tumor treatment failure. Herein, we report the development of platelet membranes as nanocarriers to co-load W18O49 nanoparticles and metformin (PM-W18O49-Met NPs). Platelet membranes can protect W18O49 from oxidation and immune evasion, and increase the accumulation of W18O49 in tumor sites via the passive EPR effect and active adhesion. Metformin can alleviate the tumor hypoxia through reducing oxygen consumption. Hence, ROS and heat generation are both greatly increased. PM-W18O49-Met NPs show the improved therapeutic effects with greatly inhibited tumor growth and induced apoptosis. Therefore, our work provides a novel strategy in bioapplication.

Keywords: Metformin; Photodynamic therapy; Photothermal therapy; Platelet membrane; Tumor hypoxia; W(18)O(49).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biomimetic Materials / chemistry*
  • Blood Platelets / metabolism*
  • Body Weight
  • Cell Line, Tumor
  • Humans
  • Hyperthermia, Induced*
  • Lymphoma / drug therapy
  • Lymphoma / pathology
  • Metformin / pharmacology*
  • Metformin / therapeutic use
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • Nanoparticles / ultrastructure
  • Oxides / pharmacology*
  • Oxides / toxicity
  • Oxygen Consumption / drug effects
  • Photochemotherapy*
  • Positron-Emission Tomography
  • Tumor Hypoxia / drug effects*
  • Tungsten / pharmacology*
  • Tungsten / toxicity

Substances

  • Antineoplastic Agents
  • Oxides
  • Metformin
  • tungsten oxide
  • Tungsten