Receptor clustering and activation by multivalent interaction through recognition peptides presented on exosomes

I Nakase1, N Ueno2, M Katayama2

  • 1Nanoscience and Nanotechnology Research Center, Research Organization for the 21st Century, Osaka Prefecture University, 1-2, Gakuen-cho, Naka-ku, Osaka 599-8570, Japan. i-nakase@21c.osakafu-u.ac.jp.

Chemical Communications (Cambridge, England)
|November 18, 2016
PubMed

Insights

Researchers developed a new exosome system to cluster cell surface receptors, activating them. This system targets cancer cells, delivering the anti-cancer protein saporin for effective cell death.

Area of Science:

  • Biotechnology
  • Cell Biology
  • Nanomedicine

Background:

  • Cell surface receptors play critical roles in cellular communication and signaling.
  • Dysregulation of receptor activity is implicated in various diseases, including cancer.
  • Exosomes are natural nanoscale vesicles involved in intercellular communication.

Purpose of the Study:

  • To develop a novel exosome-based system for inducing cell surface receptor clustering and activation.
  • To investigate the targeted delivery of therapeutic payloads to receptor-expressing cells using engineered exosomes.
  • To evaluate the efficacy of this system in inducing cancer cell death.

Main Methods:

  • Engineering exosomes to display recognition peptide segments that bind specific cell surface receptors.
  • Utilizing these engineered exosomes to induce receptor clustering and subsequent activation.
  • Loading exosomes with the cytotoxic anti-cancer protein saporin.
  • Assessing the targeted uptake of exosomes by receptor-expressing cells via endocytosis.
  • Evaluating the induction of cell death in targeted cancer cells.

Main Results:

  • Successfully demonstrated a novel system for inducing cell surface receptor clustering using engineered exosomes.
  • Achieved targeted delivery and facilitated endocytic uptake of exosomes by receptor-expressing cells.
  • Confirmed the successful delivery of the anti-cancer protein saporin into targeted cells.
  • Demonstrated significant cell death in cancer cells following exosome treatment.

Conclusions:

  • The developed exosome-based system effectively induces cell surface receptor clustering and activation.
  • Engineered exosomes provide a viable platform for targeted delivery of anti-cancer agents to specific cell populations.
  • This novel approach holds potential for targeted cancer therapy by inducing cancer cell death.

Related Concept Videos

Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.9K
Overview of Exosomes01:36

Overview of Exosomes

Exosomes are stable, lipid bilayer-enclosed vesicles capable of crossing biological barriers. They can carry a wide range of molecules required for intercellular communication. Once exosomes are released from the cell where they originated, they enter a recipient cell through various pathways such as fusion, receptor-mediated endocytosis, macropinocytosis, and phagocytosis.
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...
3.8K
Receptor-mediated Endocytosis01:20

Receptor-mediated Endocytosis

Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
10.9K
Receptor-mediated Endocytosis01:38

Receptor-mediated Endocytosis

Overview
112.7K
Receptor-Mediated Endocytosis01:20

Receptor-Mediated Endocytosis

5.6K
Antigen Processing Pathways01:31

Antigen Processing Pathways

MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...
2.8K