Afterword

Dryden, Linda

doi:10.1057/9781137500120_8

Cited by 1 publication

(1 citation statement)

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“…Clinical trials on stage IV pancreatic cancer with EV-KRAS G12D siRNA were designed (NCT03608631). Currently, several studies have investigated the delivery of chemotherapeutic drugs using tumor cell-derived exosomes since the tumor-associated antigens they contain could induce T cell-mediated immune responses; however, tumor-derived exosomes have potential risks of tumor cell invasion. , Exosomes isolated from fruits and plants have also been evaluated for clinical use to deliver curcumin from grapes to the colon to treat colon cancer . Unfortunately, these exosomes cannot enhance the host immune system and lack the benefits of immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Umbilical Cord Blood-Derived M1 Macrophage Exosomes Loaded with Cisplatin Target Ovarian Cancer In Vivo and Reverse Cisplatin Resistance

Zhang,

Wang,

Liu

et al. 2023

Mol. Pharmaceutics

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We investigated the therapeutic efficacy of umbilical cord blood (UCB)-derived M1 macrophage exosomes loaded with cisplatin (CIS) in ovarian cancer and platinum resistance. M1 macrophages were purified by using CD14 magnetic beads and characterized by flow cytometry. Our analyses included morphology, particle size, particle concentration, potential, drug loading capacity, counts of entry into cells, antitumor effect in vivo, and the ability to reverse drug resistance. A2780, SKOV3, and A2780/ DDP, SKOV3/DDP ovarian cancer cells (CIS-sensitive and CISresistant cell lines, respectively) were treated with CIS or CISloaded M1 macrophage exosomes (M1exoCISs). The encapsulation efficiency of CIS loading into M1 macrophage exosomes was approximately 30%. In vitro, M1exoCIS treatment reduced the CIS IC50 values of both A2780, SKOV3, and A2780/DDP, SKOV3/DDP cells. We evaluated the effect of M1exoCIS on tumor growth using a mouse ovarian cancer subcutaneous transplantation tumor model inoculated with A2780/DDP cells. M1exoCIS was observed in the liver, spleen, and tumor sites 24 h posttreatment; the fluorescence intensity of M1exoCIS is higher than that of CIS. After 7 days, M1exoCIS significantly inhibited the growth of subcutaneously transplanted tumors compared with CIS alone and had a longer survival time. Moreover, the toxicity test shows that M1exoCIS has less hepatorenal toxicity than CIS. To investigate the mechanism of M1exoCIS targeting, homing, and reversing drug resistance, we performed RT-PCR, Western blotting, and Proteome Profiler Human Receptor Array analyses. We found that A2780 and A2780/DDP cells expressed the integrin β1/CD29 receptor, while M1 exosomes expressed integrin β1/CD29. In addition, M1exos carries long noncoding RNA H19, implicated in PTEN protein upregulation and miR-130a and Pgp gene downregulation, leading to the reversal of CIS drug resistance. Therefore, UCBderived M1exoCIS target tumor sites of ovarian cancer in vivo and can be used to increase the CIS sensitivity and cytotoxicity.

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Section: Introductionmentioning

confidence: 99%