Docetaxel-loaded exosomes for targeting non-small cell lung cancer: preparation and evaluation in vitro and in vivo

Abstract

Non-small cell lung cancer (NSCLC) is a highly lethal disease and the majority of NSCLC patients are desperate for therapies that can effectively target their cancer and ultimately improve their overall survival. Docetaxel (DTX) represents the first-line of the antitumor agent that is used to treat NSCLC; however, it has poor solubility in water and unsatisfactory encapsulation efficiency. In our study, exosomes were isolated from A549 cancer cells by ultracentrifugation and then characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot (WB). The particle size changes of EXO and EXO-DTX were measured daily for seven days to test the stability. DTX was selected payload by electroporation (EXO-DTX). For the in vitro evaluation, cell proliferation, cell cycle, cell apoptosis, reactive oxygen species (ROS) assay and cellular uptake were evaluated in the A549 cells. Also, this study evaluated the target and therapeutic effect of DTX as an antitumor agent in vivo. As a result, EXO-DTX with a particle size of 149.5 nm were successfully prepared and the cytotoxicity of the EXO-DTX was much greater than that of DTX monomers. Exosomes significantly increased the cellular uptake in vitro evaluation and showed better targeting to tumor tissue compared to the free DTX in the mice. We also explored the potential of tumor cell-derived exosomes as a drug delivery agent to target the parent cancer. Hence, we conclude that exosomes might be used as a potential antitumor drug delivery system (DDS).

Wharton jelly-derived mesenchymal stem cell exosomes induce apoptosis and suppress EMT signaling in cervical cancer cells as an effective drug carrier system of paclitaxel

“…In addition, it has been determined that EXO-DTX triggers apoptosis, induces cell cycle arrest in the G2/M phase, and exerts an anti-cancer effect. In the in vivo experiment, it has been shown that EXO-DTX has a higher drug potential than free DTX and can be used as a good carrier system due to its faster entry into cells [ 41 ]. It is even suggested that the problems of water solubility and photosensitivity can be solved by these transport systems by loading photosensitizer anti-cancer drugs into exosomes [ 42 , 43 ].…”

Exosomes in Lung Cancer: Actors and Heralds of Tumor Development

“…Exosomes are important players in lung cancer development participating in tumor aggressiveness such as in metastasis, with organ polarization to brain and bone, angiogenesis, immune escape and even drug resistance. Due to their size and capability to transfer molecules into target recipient cells, exosomes also postulate as potential drug delivery vehicles [14]. As the tumor exosomal cargo includes molecules from the releasing cells and can be detected in circulation, exosomes can serve as non-invasive biomarkers providing a potential alternative or at least, a complementary tool to conventional biopsy with additional advantages in the diagnosis, prognosis, therapy election and follow-up.…”

“…Consequently, tumor-derived exosomes play an important role in tumor development. Therefore, their analysis can help to gain a deeper knowledge of tumor biology and they can even be targets for drug therapy or delivery [14]. In addition, exosomes are very attractive due to their potential role as cancer biomarkers that could improve the management of cancer patients in general, and specifically, in lung cancer patients.…”

Lipid-Based Nanovesicular Drug Delivery Systems

“…Neuroprotection and ischemia-reperfusion injury treatment [260] Inhibit the phosphorylation of Tau protein [261] Exosomes from mesenchymal stem cells Attenuate the progression of osteoarthritis [262] EVs from HEK293 cells Myocardial infarction treatment [263] Exosomes from bone marrow-derived mesenchymal stem cells Cerebral ischemia treatment [264] Exosomes from HEK293 cells Curcumin and RAGE-binding peptide Acute lung injury treatment [265] EVs from smooth muscle cells Cystatin C Protection and healing of the nervous system in different neurotoxic conditions [266] Exosomes from lung cancer Docetaxel Non-small cell lung cancer treatment [267] Exosomes from cervical cancer Cervical cancer treatment [268] Exosomes from blood samples Dopamine Parkinson's disease treatment [269] EVs from macrophages Doxorubicin Metastatic ovarian cancer treatment [270] Exosomes from mesenchymal stem cells Colorectal cancer treatment [271] Exosomes from human glioma Glioma treatment [272] Milk-derived exosomes Cancer treatment [273] Exosomes from HEK293 cells Cancer treatment [274] Exosomes from bone marrow-derived mesenchymal stem cells Osteosarcoma treatment [275] Exosomes from colon cancer Colorectal cancer treatment [276] Exosomes from human breast and ovarian cancer Breast and ovarian cancer treatment [277] Exosomes from macrophages Edaravone Permanent middle cerebral artery occlusion treatment [278] Exosomes from human fetal lung fibroblasts Erastin Triple-negative breast cancer therapy [279] Exosomes from pancreatic cells Gemcitabine Pancreatic cancer treatment [280] EVs from human plasma Imperialine Non-small cell lung cancer treatment [281] EVs from human umbilical vascular endothelial cells…”