1. Academic Validation
  2. Responsive and activable nanomedicines for remodeling the tumor microenvironment

Responsive and activable nanomedicines for remodeling the tumor microenvironment

  • Nat Protoc. 2021 Jan;16(1):405-430. doi: 10.1038/s41596-020-00421-0.
Yinlong Zhang  # 1 2 Xuexiang Han  # 1 3 Guangjun Nie 4 5 6
Affiliations

Affiliations

  • 1 CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, China.
  • 2 Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, China.
  • 3 Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
  • 4 CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, China. niegj@nanoctr.cn.
  • 5 Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, China. niegj@nanoctr.cn.
  • 6 GBA Research Innovation Institute for Nanotechnology, Guangdong, China. niegj@nanoctr.cn.
  • # Contributed equally.
Abstract

Here we describe two protocols for the construction of responsive and activable nanomedicines that regulate the tumor microenvironment (TME). The TME is composed of all non-cellular and cellular components surrounding a tumor, including the surrounding blood vessels, immune cells, fibroblasts, signaling molecules, and extracellular matrix and has a crucial role in tumor initiation, growth, and metastasis. Owing to the relatively stable properties of the TME compared to tumor cells, which exhibit frequent genetic mutations and epigenetic changes, therapeutic strategies targeting the TME using multifunctional nanomedicines hold great potential for anti-tumor therapy. By regulating tumor-associated platelets and pancreatic stellate cells (PSCs), the two major players in the TME, we can effectively manipulate the physiological barriers for enhanced Drug Delivery and significantly improve the tumor penetration and therapeutic efficacy of chemotherapeutics. The preparation and characterization of the multifunctional nanoparticles takes ~10 h for tumor-associated platelet regulation and 16 h for PSC regulation. These nanoformulations can be readily applied to regulate other components in the TME to realize synergistic or additive anti-tumor activity.

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