A novel macrophage-mediated biomimetic delivery system with NIR-triggered release for prostate cancer therapy

J Nanobiotechnology. 2019 Jul 10;17(1):83. doi: 10.1186/s12951-019-0513-z.

Abstract

Background: Macrophages with tumor-tropic migratory properties can serve as a cellular carrier to enhance the efficacy of anti neoplastic agents. However, limited drug loading (DL) and insufficient drug release at the tumor site remain the main obstacles in developing macrophage-based delivery systems. In this study, we constructed a biomimetic delivery system (BDS) by loading doxorubicin (DOX)-loaded reduced graphene oxide (rGO) into a mouse macrophage-like cell line (RAW264.7), hoping that the newly constructed BDS could perfectly combine the tumor-tropic ability of macrophages and the photothermal property of rGO.

Results: At the same DOX concentration, the macrophages could absorb more DOX/PEG-BPEI-rGO than free DOX. The tumor-tropic capacity of RAW264.7 cells towards RM-1 mouse prostate cancer cells did not undergo significant change after drug loading in vitro and in vivo. PEG-BPEI-rGO encapsulated in the macrophages could effectively convert the absorbed near-infrared light into heat energy, causing rapid release of DOX. The BDS showed excellent anti-tumor efficacy in vivo.

Conclusions: The BDS that we developed in this study had the following characteristic features: active targeting of tumor cells, stimuli-release triggered by near-infrared laser (NIR), and effective combination of chemotherapy and photothermotherapy. Using the photothermal effect produced by PEG-BPEI-rGO and DOX released from the macrophages upon NIR irradiation, MAs-DOX/PEG-BPEI-rGO exhibited a significant inhibitory effect on tumor growth.

Keywords: Biomimetic delivery system (BDS); Cancer therapy; Macrophage; Photothermal effect.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry*
  • Biomimetic Materials / chemistry*
  • Cell Line, Tumor
  • Doxorubicin / administration & dosage
  • Doxorubicin / chemistry
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Graphite / chemistry
  • Humans
  • Hyperthermia, Induced
  • Infrared Rays
  • Lasers
  • Macrophages / metabolism*
  • Male
  • Mice, Inbred BALB C
  • Polyethylene Glycols / chemistry
  • Polyethyleneimine / analogs & derivatives
  • Polyethyleneimine / chemistry
  • Prostatic Neoplasms / drug therapy*
  • Tissue Distribution

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • branched polyethyleneimine-block-polyethylene glycol
  • graphene oxide
  • Polyethylene Glycols
  • Graphite
  • Doxorubicin
  • Polyethyleneimine