Journal Article

Engineering a HEK-293T exosome-based delivery platform for efficient tumor-targeting chemotherapy/internal irradiation combination therapy

Li, Ning, Zhang, Wenxin, Wang, Shen, Hou, Shasha, Meng, Zhaowei, Wang, Congcong, Jia, Qiang, Tan, Jian, Zhang, Ruiguo, Li, Yutian, Wang, Renfei

2022

Overview

Exosomes are nanoscale monolayer membrane vesicles that are actively endogenously secreted by mammalian cells. Currently, multifunctional exosomes with tumor-targeted imaging and therapeutic potential have aroused widespread interest in cancer research. Herein, we developed a multifunctional HEK-293T exosome-based targeted delivery platform by engineering HEK-293T cells to express a well-characterized exosomal membrane protein (Lamp2b) fused to the αv integrin-specific iRGD peptide and tyrosine fragments. This platform was loaded with doxorubicin (Dox) and labeled with radioiodine-131 ( 131 I) using the chloramine-T method. iRGD exosomes showed highly efficient targeting and Dox delivery to integrin αvβ3-positive anaplastic thyroid carcinoma (ATC) cells as demonstrated by confocal imaging and flow cytometry in vitro and an excellent tumor-targeting capacity confirmed by single-photon emission computed tomography-computed tomography after labeling with 131 I in vivo. In addition, intravenous injection of this vehicle delivered Dox and 131 I specifically to tumor tissues, leading to significant tumor growth inhibition in an 8505C xenograft mouse model, while showing biosafety and no side effects. These as-developed multifunctional exosomes (denoted as Dox@iRGD-Exos- 131 I) provide novel insight into the current treatment of ATC and hold great potential for improving therapeutic efficacy against a wide range of integrin αvβ3-overexpressing tumors. Graphical Abstract

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Anaplastic thyroid carcinoma / Angiogenesis / Animals / Antibiotics / Biomedical engineering / Biotechnology / Cancer / Cancer research / Cancer therapies / Care and treatment / Cell culture / Cell organelles / Chemistry / Chemistry and Materials Science / Chemotherapy / Chloramine-T / Combination therapy / Combined modality therapy / Computed tomography / Doxorubicin / Drug delivery systems / Drugs / Exosome / Exosomes / Exosomes - metabolism / FDA approval / Flow cytometry / Growth inhibition / Health aspects / HEK293 Cells / Humans / Integrin alphaVbeta3 - metabolism / Intravenous administration / Iodine 131 / Iodine radioisotopes / Iodine Radioisotopes - analysis / Iodine Radioisotopes - metabolism / iRGD peptide / Irradiation / Mammalian cells / Medical imaging / Membrane proteins / Membrane vesicles / Membranes / Metastasis / Methods / Mice / Molecular Medicine / Nanotechnology / Neoplasms - drug therapy / Neoplasms - radiotherapy / Oncology, Experimental / Peptides / Photon emission / Polyclonal antibodies / Proteins / Radiation / Radioiodine-131 / Radiotherapy / RNA polymerase / Side effects / Thyroid / Thyroid cancer / Thyroid carcinoma / Tumor targeting / Tumors / Tyrosine / Vehicles / Xenografts / Xenotransplantation