In Vivo Monocyte/Macrophage-Hitchhiked Intratumoral Accumulation of Nanomedicines for Enhanced Tumor Therapy

J Am Chem Soc. 2020 Jan 8;142(1):382-391. doi: 10.1021/jacs.9b11046. Epub 2019 Dec 17.

Abstract

The inner region of solid tumors is found to be high-pressure, hypoxic, and immunosuppressive, providing a breeding ground for tumor aggressiveness and metastasis. While intratumoral accumulation of nanomedicines combined with immunomodulation would significantly enhance therapeutic efficacy, such potential is challenged by the compressed environment and distinct heterogeneity of the tumor bulk. By using an apoptotic body (AB) as the carrier, we develop an effective and universal intratumoral nanomedicine delivery system for the long-lasting remission of tumors. Our results show that the AB-encapsulated nanomedicine (using CpG immunoadjuvant-modified gold-silver nanorods as a model), after intravenous injection, can be specifically phagocytosed by inflammatory Ly-6C+ monocytes, which then actively infiltrate the tumor center via their natural tumor-homing tendency. With the integration of AB-facilitated intratumoral accumulation, the nanorod-based photothermal effect, and CpG-promoted immunostimulation, this cell-mediated delivery system can not only efficiently ablate primary tumors but also elicit a potent immunity to prevent tumors from metastasizing and recurring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Drug Delivery Systems
  • Gold / chemistry
  • Humans
  • Macrophages / metabolism*
  • Metal Nanoparticles / administration & dosage
  • Metal Nanoparticles / chemistry
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / metabolism*
  • Nanomedicine*
  • Neoplasm Metastasis / prevention & control
  • Neoplasm Recurrence, Local / prevention & control
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Phototherapy / methods
  • Xenograft Model Antitumor Assays

Substances

  • Adjuvants, Immunologic
  • Gold