Role of exosomes in tumour growth, chemoresistance and immunity: state-of-the-art

Hosseinikhah, Seyedeh Maryam; Gheybi, Fatemeh; Moosavian, Seyedeh Alia; Shahbazi, Mohammad‐Ali; Jaafari, Mahmoud Reza; Kesharwani, Prashant; Alavizadeh, Seyedeh Hoda; Sahebkar, Amirhossein

doi:10.1080/1061186x.2022.2114000

Cited by 18 publications

(12 citation statements)

References 163 publications

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“…Exosomes, due to its antigen-presenting properties and drug-loading properties, are widely used as drug carriers in researches [12]. In previous studies, Zhang and Liu discussed the application of exosome on drug delivery as carriers for DNA, messenger RNA, microRNA, smallinterfering RNA, and other nucleic acids [20].…”

Section: Discussionmentioning

confidence: 99%

“…The mEXOs and siKeap1 were mixed in a ratio of 1:1 (mass/mass) in PBS, and the final concentration of mEXOs in the mixture was 4 μg/ml. The sonication settings [12] were: 20% amplitude, 6 on/ off cycles of 30 s, with a cooling time of 2 min between each cycle. After sonication, the unencapsulated siKeap1 in the supernatant was measured using a microplate reader at 260 nm, and the siKeap1 load was calculated by the weight ratio of encapsulated siKeap1 to the nanovesicles loaded with siKeap1 [13].…”

Section: Ultrasonic Technologymentioning

confidence: 99%

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Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress

Xiang

Chen

Jiang

et al. 2023

Drug Deliv. and Transl. Res.

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Diabetic wounds are a serious complication of diabetes mellitus (DM) that can lead to persistent infection, amputation, and even death. Prolonged oxidative stress has been widely recognized as a major instigator in the development of diabetic wounds; therefore, oxidative stress is considered a promising therapeutic target. In the present study, Keap1/Nrf2 signaling was confirmed to be activated in streptozotocin (STZ)-induced diabetic mice and methylglyoxal (MGO)-treated human umbilical vein endothelial cells (HUVECs). Knockdown of Keap1 by siRNA reversed the increase in Keap1 levels, promoted the nuclear translocation of Nrf2, and increased the expression of HO-1, an antioxidant protein. To explore therapeutic delivery strategies, milk-derived exosomes (mEXOs) were developed as a novel, efficient, and non-toxic siRNA carrier. SiRNA-Keap1 (siKeap1) was loaded into mEXOs by sonication, and the obtained mEXOs-siKeap1 were found to promote HUVEC proliferation and migration while relieving oxidative stress in MGO-treated HUVECs. Meanwhile, in a mouse model of diabetic wounds, injection of mEXOs-siKeap1 significantly accelerated diabetic wound healing with enhanced collagen formation and neovascularization. Taken together, these data support the development of Keap1 knockdown as a potential therapeutic strategy for diabetic wounds and demonstrated the feasibility of mEXOs as a scalable, biocompatible, and cost-effective siRNA delivery system. Graphical Abstract The therapeutic effect of siKeap1-loaded mEXOs on diabetic wound healing was assessed. First, we found that the expression of Keap1 was upregulated in the wounds of diabetic mice and in human umbilical vein endothelial cells (HUVECs) pretreated with methylglyoxal (MGO). Next, we extracted exosomes from raw milk by differential centrifugation and loaded siKeap1 into milk-derived exosomes by sonication. The in vitro application of the synthetic complex (mEXOs-siKeap1) was found to increase the nuclear localization of Nrf2 and the expression of the antioxidant protein HO-1, thus reversing oxidative stress. Furthermore, in vivo mEXOs-siKeap1 administration significantly accelerated the healing rate of diabetic wounds (Scheme 1). Scheme 1 Schematic diagram. A Synthesis of mEXOs-siKeap1 complex. B Mechanism of mEXOs-siKeap1 in vitro. C The treatment effect of mEXOs-siKeap1 on an in vivo mouse model of diabetic wounds Supplementary Information The online version contains supplementary material available at 10.1007/s13346-023-01306-x.

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Section: Discussionmentioning

confidence: 99%

Section: Ultrasonic Technologymentioning

confidence: 99%

Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress

Xiang

Chen

Jiang

et al. 2023

Drug Deliv. and Transl. Res.

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“…They enhance the development of the pre-metastatic niche to promote tumor colonization and play a pivotal role in the early diagnosis and evaluation of future metastatic development ( Luo et al, 2023 ). Exosomes are used as drug carriers (e.g., chemotherapy and miRNA) and as biomarkers because they exhibit antigen-presenting traits that have a crucial function in cancer immunotherapy ( Hosseinikhah et al, 2023 ). Prakriti [phenotype-associated Ayurveda constitution] is linked with other fields like genomics, physiology, psychology, and therapeutics.…”

Section: Conclusion and Future Perspectivementioning

confidence: 99%

Exosomal miRNAs as novel avenues for breast cancer treatment

et al. 2023

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Breast cancer is the most commonly diagnosed cancer and a leading cause of death in women worldwide. It is a heterogeneous disease, as shown by the gene expression profiles of breast cancer samples. It begins in milk-producing ducts, with a high degree of diversity between and within tumors, as well as among cancer-bearing individuals. The enhanced prevalence of breast cancer is influenced by various hormonal, lifestyle, and environmental factors, and very early onset of the disease correlates strongly with the risk of local and distant recurrence. Many subtypes are difficult to treat with conventional therapeutic modalities, and therefore, optimal management and early diagnosis are the first steps to minimizing the mortality linked with breast cancer. The use of newer methods of nanotechnology extends beyond the concept of synthesizing drug delivery mechanisms into the creation of new therapeutics, such as delivering chemotherapeutics with nanomaterial properties. Exosomes, a class of nanovesicles, are emerging as novel tools for deciphering the patient-specific proteins and biomarkers across different disease models, including breast cancer. In this review, we address the role of exosomal miRNA in breast cancer diagnosis and treatment.

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“…The mEXOs and siKeap1 were mixed in a ratio of 1:1 (mass/mass) in PBS, and the nal concentration of mEXOs in the mixture was 4 μg/ml. For the concrete sonication method, the following settings [20] were 20% amplitude, 6 on/off cycles of 30 seconds, with a cooling time of 2 min between each cycle. After sonication, the solution was incubated at 37 ° C for 60 min to restore the exosome membrane.…”

Section: Ultrasonic Technologymentioning

confidence: 99%

Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress

Xiang

Chen

Jiang

et al. 2022

Preprint

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Diabetic wound, as a serious complication of diabetes mellitus (DM), leads to persistent infection, amputation and even death. Prolonged oxidative stress has been widely recognized as the main cause of diabetic wound and is considered as hopeful therapeutic target. In the present study, Keap1/Nrf2 signaling was confirmed to be activated in streptozotocin (STZ)-induced diabetic mice and methylglyoxal (MGO)-treated human umbilical vein endothelial cells (HUVEC). Knockdown of Keap1 by siRNA attenuated the raised Keap1 level, promoted the nuclear transfer of Nrf2, and then facilitated the expression of HO-1, an antioxidant protein. Then the milk-derived exosomes (mEXOs) were developed as a novel, efficient and non-toxic siRNA carrier. SiRNA-Keap1 (siKeap1) was loaded into mEXOs through ultrasonic technique, which promoted HUVEC proliferation, migration and relieved oxidative stress in MGO-treated HUVEC. In the meantime, the injection of mEXOs-siKeap1 significantly accelerated the diabetic wound healing with enhanced collagen formation and neovascularization in mice models. Totally, the present study puts forward a potential treatment for diabetic wound and proved the feasibility of mEXOs as a scalable, biocompatible, and cost-effective siRNA delivery system.

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Role of exosomes in tumour growth, chemoresistance and immunity: state-of-the-art

Cited by 18 publications

References 163 publications

Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress

Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress

Exosomal miRNAs as novel avenues for breast cancer treatment

Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress

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