<p>Targeted delivery of doxorubicin to HER2 positive tumor models</p>

Abstract

Background Exosomes are natural nanovesicles with unique characteristics, such as long circulating half-life, the intrinsic ability to target tissues, biocompatibility, and minimal or no inherent systemic toxicity. Mesenchymal stem cells produce large amounts of exosomes with regenerative properties and more stability in human plasma. TUBO breast cancer cell lines overexpress rat HER2/neu protein. Methods Targeted exosomes were isolated from transduced bone marrow mesenchymal stem cells. Doxorubicin was encapsulated into exosomes by electroporation. Flow cytometry was used to assess the attachment of exosomes to the target cells. The in vitro cytotoxicity effect of targeted doxorubicin-loaded exosomes on TUBO cells was determined using MTT assay. Selective delivery of doxorubicin to tumor tissues was analyzed by measuring the auto-fluorescence of doxorubicin by in vivo imaging system. Moreover, tumor growth inhibition and body weight were monitored following injection of free doxorubicin, and targeted and untargeted doxorubicin-loaded exosomes in a TUBO breast cancer model. Finally, mouse tissues were examined for the presence of intrinsic fluorescence of doxorubicin. Results Flow cytometry results revealed significant differences in binding of targeted exosomes to HER2-positive (46.05%) and HER2-negative (13.9%) cells. The results of MTT assay showed that cytotoxicity of targeted doxorubicin-loaded exosomes was higher than free doxorubicin at 72 hours. Selective distribution of targeted doxorubicin-loaded exosomes in the target tissues of the murine breast cancer model suggested specific delivery of doxorubicin by targeted exosomes, rather than untargeted exosomes. Free doxorubicin and untargeted doxorubicin-loaded exosomes showed insignificant effects, whereas targeted doxorubicin-loaded exosomes reduced the tumor growth rate. Conclusion Herein, we report efficient delivery of targeted doxorubicin-loaded exosomes in vitro, corroborated with a significant reduction of murine breast cancer model tumor growth rate.

<p>Cancer-Derived Exosomes: Their Role in Cancer Biology and Biomarker Development</p>

“…116 There are growing interests in investigating engineered exosomes as potential therapeutic vehicles or an active drug delivery system. [117][118][119][120][121][122][123] Making use of the exosomal organotropic characteristics, exosomes loaded with therapeutic compounds could be employed to target a recipient cell to carry out gene therapy selectively.…”

Extracellular vesicles derived from different sources of mesenchymal stem cells: therapeutic effects and translational potential

“…Researchers demonstrated that with the chimeric LAMP2b-DARP in protein on the surface of exosomes, DOX-exo showed more efficient binding to HER2-positive TUBO cells. The designed exosomes increased the accumulation of DOX in the tumor site and reduce the growth rate of breast cancer cells [56].…”

“…The main part of extracting is the donor's abdomen and buttocks. Then special culture medium was used for filtrating MSCs [56].…”

<p>Preparation and Evaluation of Doxorubicin-Loaded PLA–PEG–FA Copolymer Containing Superparamagnetic Iron Oxide Nanoparticles (SPIONs) for Cancer Treatment: Combination Therapy with Hyperthermia and Chemotherapy</p>

“…[35][36][37][38] Loading of doxorubicin in nanoparticles increases its bioavailability and anti-tumor activity, DNA affinity and reduces its severe side-effects. [39][40][41] The idea of combined therapy by mixing more than two therapeutic agents in the form of a multifunctional nanoparticle platform has been introduced as a strategy to gain synergistic effects of therapeutic agents on disease treatment. 42,43 Hyperthermia or thermal therapy, ie raising the temperature of tumor tissues to 40-45°C, has provided acceptable benefits and is a promising approach for cancer treatment.…”