Tumor associated macrophages and angiogenesis dual-recognizable nanoparticles for enhanced cancer chemotherapy

Nanomedicine. 2018 Apr;14(3):651-659. doi: 10.1016/j.nano.2017.12.018. Epub 2018 Jan 10.

Abstract

Tumor-associated macrophages (TAMs) and angiogenesis are increasingly considered as the pivotal factors that affect tumor progress. Herein, we developed the paclitaxel (PTX)-loaded nanoparticles (NP/PTX) and decorated it with an innovative peptide YI (YINP/PTX) for simultaneously targeting delivery of drug to TAMs and angiogenesis. We demonstrated that the modification of YI peptide significantly enhanced the internalization of nanoparticles by cells and accumulation of nanoparticles in tumor tissues, but down regulated the distribution of them in normal tissues especially the liver. We also made a confirmation that the YI peptide decorated nanoparticles had an excellent co-localization with TAMs and angiogenesis in vivo. Finally, in the HT-26 colorectal tumor-bearing mice, a pharmacodynamic evaluation was performed and results showed that the YINP/PTX was more effective than other PTX formulations in anti-tumor growth. These results together suggested that the prepared nanoparticles are promising in targeting delivery of chemotherapeutics to tumor microenvironment for enhancing tumor therapy effect.

Keywords: Angiogenesis; Nanoparticles; Tumor microenvironment; Tumor therapy; Tumor-associated macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A1 / chemistry
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / blood supply
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Drug Delivery Systems*
  • Humans
  • Macrophages / pathology*
  • Mice
  • Mice, Nude
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Neovascularization, Pathologic*
  • Paclitaxel / administration & dosage
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacology*
  • Peptide Fragments / chemistry*
  • Tumor Cells, Cultured
  • Tumor Microenvironment
  • Xenograft Model Antitumor Assays

Substances

  • Annexin A1
  • Antineoplastic Agents
  • Peptide Fragments
  • Paclitaxel