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Published on: May 24, 2019
Chiral Supramolecular Nanofibers Regulated Tumor-Derived Exosomes Secretion for Constructing an Anti-Tumor
Beibei Wu1, Xiaoqiu Dou1, Yu Zhao1
1State Key Lab of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200230, P. R. China.
Abstract:
Tumor-derived exosomes (TDEs) induced extracellular microenvironment has recently been validated to be critical for tumor progression and metastasis, however, remodeling it for oncotherapy still remains a major challenge due to difficulty in regulation of TDEs secretion. Herein, the supramolecular chiral nanofibers, composed of L/D-phenylalanine derivates (L/D-Phe) and linear hyaluronic acid (HA), are successfully employed to construct TDEs induced anti-tumor extracellular microenvironment. The left-handed L-Phe @HA nanofibers significantly inhibit TDEs secretion into extracellular microenvironment, which results in suppression of tumor proliferation and metastasis in vitro and vivo. Biological assays and theoretical modeling reveal that these results are mainly attributed to strong adsorption of the key exosomes transporters (Ras-related protein Rab-27A and synaptosome-associated protein 23) on left-handed L-Phe @HA nanofibers via enhanced stereoselective interaction, leading to degradation and phosphorylated dropping of exosomes transporters. Subsequently, transfer function of exosomes transporters is limited, which causes remarkable inhibition of TDEs secretion. These findings provide a promising novel insight of chiral functional materials to establish an anti-tumor extracellular microenvironment via regulation of TDEs secretion.
Insights
Chiral nanofibers effectively block tumor-derived exosome secretion by targeting exosome transporters. This novel approach suppresses tumor growth and metastasis, offering a new strategy for cancer therapy.
Area of Science:
- Biomaterials Science
- Cancer Biology
- Nanotechnology
Background:
- Tumor-derived exosomes (TDEs) are crucial for tumor progression and metastasis.
- Remodeling the tumor extracellular microenvironment for cancer therapy is challenging due to difficulties in regulating TDE secretion.
Purpose of the Study:
- To develop a supramolecular chiral nanofiber system to construct an anti-tumor extracellular microenvironment by regulating TDE secretion.
- To investigate the mechanism by which chiral nanofibers inhibit TDE secretion and suppress tumor progression.
Main Methods:
- Synthesis of supramolecular chiral nanofibers from L/D-phenylalanine derivatives (L/D-Phe) and hyaluronic acid (HA).
- In vitro and in vivo assays to evaluate the anti-tumor effects of L-Phe @HA nanofibers.
- Biological assays and theoretical modeling to elucidate the interaction between nanofibers and exosome transporters.
Main Results:
- Left-handed L-Phe @HA nanofibers significantly inhibited TDE secretion.
- Tumor proliferation and metastasis were suppressed in vitro and in vivo.
- Strong adsorption of exosome transporters (Rab-27A and synaptosome-associated protein 23) on L-Phe @HA nanofibers via stereoselective interaction was observed, leading to transporter degradation and reduced TDE secretion.
Conclusions:
- Chiral functional materials can establish an anti-tumor extracellular microenvironment by regulating TDE secretion.
- L-Phe @HA nanofibers offer a promising strategy for oncotherapy by inhibiting TDEs.
- Stereoselective interactions are key to the mechanism of TDE secretion inhibition.
