A mutually beneficial macrophages-mediated delivery system realizing photo/immune therapy

J Control Release. 2022 Jul:347:14-26. doi: 10.1016/j.jconrel.2022.04.038. Epub 2022 May 4.

Abstract

The accumulation of nanomedicines in tumor tissues determines their therapeutic efficacy. We herein exploit the tropism of macrophages to improve the accumulation and retention time of nanomedicine at tumors. Interestingly, macrophages are not merely as transporters, but killers activated by nanomedicine. The system(M@C-HA/ICG) was established by decorating macrophages with hyaluronic acid-modified hollow mesoporous carbon (C) nanoparticles loading indocyanine green (ICG). Notably, C nanoparticles with superior photothermal conversion capability not merely guarantee the efficient delivery of ICG through high drug loading efficiency and inhibiting the premature leaky, but effectually activate the polarization of macrophages. The results exhibited that those activated macrophages could release pro-inflammatory cytokines (NO, TNF-α, IL-12), while M@C-HA/ICG afforded about 2-fold higher tumor accumulation compared with pure nanoparticle C-HA/ICG and produced heat and singlet oxygen (1O2) under irradiation of an 808 nm laser, realizing the combination of photodynamic therapy (PDT), photothermal therapy (PTT) and cytokines-mediated immunotherapy. Specially, we also investigated the relationship of singlet oxygen (1O2) or temperature and tumor-killing activity for understanding the specific effectual procedure of PDT/PTT synergistic therapy. Overall, we firstly established an "all active" delivery system integrating the features of nanomedicine with biological functions of macrophages, providing a novel insight for cell-mediated delivery platform and tumor targeted multimodality anti-cancer therapy.

Keywords: Cell-based delivery; Immunotherapy; Macrophage polarization; Mesoporous carbon nanoparticles; Phototherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cytokines
  • Humans
  • Indocyanine Green / therapeutic use
  • Macrophages
  • Nanoparticles* / therapeutic use
  • Neoplasms* / drug therapy
  • Photochemotherapy* / methods
  • Phototherapy / methods
  • Singlet Oxygen

Substances

  • Cytokines
  • Singlet Oxygen
  • Indocyanine Green