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Photoactivatable Silencing Extracellular Vesicle (PASEV) Sensitizes Cancer Immunotherapy

Mei Lu1,2, Haonan Xing2,3, Wanxuan Shao1

  • 1Advanced Research Institute of Multidisciplinary Science, School of Life Science, School of Medical Technology (Institute of Engineering Medicine), Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, China.

Advanced Materials (Deerfield Beach, Fla.)
|July 6, 2022
PubMed

Insights

This study introduces photoactivatable silencing extracellular vesicles (PASEVs) to enhance cancer immunotherapy by silencing p21-Activated kinase 4 (PAK4) and boosting immune responses within the tumor microenvironment (TME).

Area of Science:

  • Oncology
  • Immunology
  • Nanomedicine

Background:

  • Cancer immunotherapy faces challenges due to poor immune cell infiltration and low immunogenicity in the tumor microenvironment (TME).
  • p21-Activated kinase 4 (PAK4) is identified as a key factor contributing to immune exclusion within tumors.

Purpose of the Study:

  • To develop a novel photoactivatable silencing extracellular vesicle (PASEV) system for sensitized cancer immunotherapy.
  • To overcome limitations of insufficient immune infiltration and poor immunogenicity in the TME.

Main Methods:

  • siPAK4 (small interfering RNA against PAK4) was combined with a ROS-sensitive polymer and M1 macrophage-derived extracellular vesicles to create PASEVs.
  • PASEVs were designed for targeted delivery, accumulation, and ROS-responsive release of siPAK4.
  • PASEVs utilize phototherapy to prime the TME and enhance immune activation.

Main Results:

  • PASEVs effectively delivered siPAK4, leading to potent PAK4 silencing.
  • The treatment successfully boosted intratumoral immune cell infiltration and immune activation.
  • Combined immunotherapy demonstrated robust anticancer immunity in preclinical models.

Conclusions:

  • PASEVs offer a dual-action approach to enhance cancer immunotherapy by silencing immune-suppressive factors and stimulating anti-tumor immunity.
  • This strategy shows significant promise for improving patient responses to cancer treatment by optimizing the TME.
Keywords:
PAK4RNA interferencecancer immunotherapyextracellular vesiclesimmunogenic phototherapy

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