Engineering blood exosomes for tumor-targeting efficient gene/chemo combination therapy.

Theranostics
Qi ZhanChunsheng Kang

Abstract

Rationale: Developing an effective nanoplatform to realize 'multi-in-one' is essential to broaden the therapeutic potential of combination therapy. Exosomes are ideal candidates since their intrinsic abilities of integrating multiple contents and functions. However, only limited efforts have been devoted to engineering exosomes to integrate the needed properties, also considering the safety and yield, for tumor-targeted and efficient gene/chemo combination therapy. Methods: Herein, by manipulating the exosome membrane, blood exosomes with high abundance and safety are engineered as a versatile combinatorial delivery system, where the doxorubicin (Dox) and cholesterol-modified miRNA21 inhibitor (miR-21i) are co-embedded into the lipid bilayer of exosomes, and the magnetic molecules and endosomolytic peptides L17E are bind to the exosome membrane through ligand-receptor coupling and electrostatic interactions, respectively. Results: It is proved that such engineering strategy not only preserves their intrinsic features, but also readily integrates multiple properties of tumor targeting, efficient transfection and gene/chemo combination therapy into blood exosomes. The lipid bilayer structure of exosomes allows them to co-load Dox...Continue Reading

Citations

Dec 29, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Yu-Shui MaDa Fu
Jan 8, 2021·Endocrinology·Fernanda G KugeratskiRaghu Kalluri
Feb 3, 2021·Molecular and Cellular Biochemistry·Yifei YuGuangfan Chi
Feb 9, 2021·Bioactive Materials·Benilde AdrianoMurali M Yallapu
Feb 16, 2021·The AAPS Journal·Akhil SrivastavaRajagopal Ramesh
Mar 2, 2021·Advanced Materials·Xu ZhangHélder A Santos
Feb 12, 2021·Endocrinology·Fernanda G KugeratskiRaghu Kalluri
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Isha GauravZhijun Yang
Jun 16, 2021·Colloids and Surfaces. B, Biointerfaces·Su-Hyun KwonSukho Park
Aug 16, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Sangrok HanMinhyung Lee

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Methods Mentioned

BETA
dynamic light scattering
fluorescence imaging
electrophoresis
transfection
flow cytometry
protein assay
ELISA
protein determination assay
fluorescence spectroscopy
dynamic dialysis

Software Mentioned

Nanoparticles Tracking Analysis ( NTA )
GraphPad Prism
ImageJ

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