Cannabidiol loaded extracellular vesicles sensitize triple-negative breast cancer to doxorubicin in both in-vitro and in vivo models

Patel, Nilkumar; Kommineni, Nagavendra; Surapaneni, Sunil Kumar; Kalvala, Anil Kumar; Yaun, Xuegang; Gebeyehu, Aragaw; Arthur, Peggy; Duke, Leanne C.; York, Sara B.; Bagde, Arvind; Meckes, David G.; Singh, Mandip

doi:10.1016/j.ijpharm.2021.120943

Cited by 34 publications

(32 citation statements)

References 140 publications

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“…Conditioned media from early and late organoids were collected during every media change (twice weekly) and stored at 4°C. Retinal organoids conditioned media were then treated with polyethylene glycol 6000 (80503, VWR International, USA) to extract the EVs which were further subjected to differential ultracentrifugation processes as described previously [28, 43, 44]. Briefly, the EV-containing conditioned media were centrifuged at 500 xg for 5 min at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Biophysical, Molecular and Proteomic profiling of Human Retinal Organoids derived Exosomes

Arthur

Kandoi

Lee

et al. 2022

Preprint

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Extracellular vesicles (EVs) are phospholipid bilayer-bound particles released by cells that play a role in cell-cell communication, signal transduction, and extracellular matrix remodeling. There is a growing interest in EVs for ocular applications as therapeutics, biomarkers, and drug delivery vehicles. EVs secreted from mesenchymal stem cells (MSCs) have shown to provide therapeutic benefits in ocular conditions. However, very little is known about the properties of bioreactors cultured-3D human retinal organoids secreted EVs. This study provides a comprehensive morphological, nanomechanical, molecular, and proteomic characterization of retinal organoid EVs and compares it with human umbilical cord (hUC) MSCs. Nanoparticle tracking analysis indicated the average size of EV as 100–250 nm. Atomic force microscopy showed that retinal organoid EVs are softer and rougher than the hUCMSC EVs. Gene expression analysis by qPCR showed a high expression of exosome biogenesis genes in late retinal organoids derived EVs (>120 days). Immunoblot analysis showed highly expressed exosomal markers Alix, CD63, Flotillin-2, HRS and Hsp70 in late retinal organoids compared to early retinal organoids EVs (<120 days). Protein profiling of retinal organoid EVs displayed a higher differential expression of retinal function-related proteins and EV biogenesis/marker proteins than hUCMSC EVs, implicating that the use of retinal organoid EVs may have a superior therapeutic effect on retinal disorders. This study adds supplementary knowledge on the properties of EVs secreted by retinal organoids and suggests their potential use in the diagnostic and therapeutic treatments for ocular diseases.

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Section: Methodsmentioning

confidence: 99%

Biophysical, Molecular and Proteomic profiling of Human Retinal Organoids derived Exosomes

Arthur

Kandoi

Lee

et al. 2022

Preprint

Self Cite

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“…Hence, Tu-EVs can be used as drug carriers in oncology owing to their excellent targeting capability with respect to parental cells. For instance, breast cancer cell-derived EVs loaded with doxorubicin can target breast cancer cells and inhibit tumor invasion by suppressing tumor angiogenesis [ 158 ]. Moreover, EVs derived from B16 melanoma cells transfected with a plasmid encoding the Mycobacterium tuberculosis antigen early secretory antigenic target-6 (ESAT-6) were found to be able to significantly inhibit tumor growth in syngeneic B16 tumor-bearing mice [ 159 ].…”

Section: Engineered Evs In Tumor Therapymentioning

confidence: 99%

Application of engineered extracellular vesicles for targeted tumor therapy

et al. 2022

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All cells, including prokaryotes and eukaryotes, could release extracellular vesicles (EVs). EVs contain many cellular components, including RNA, and surface proteins, and are essential for maintaining normal intercellular communication and homeostasis of the internal environment. EVs released from different tissues and cells exhibit excellent properties and functions (e.g., targeting specificity, regulatory ability, physical durability, and immunogenicity), rendering them a potential new option for drug delivery and precision therapy. EVs have been demonstrated to transport antitumor drugs for tumor therapy; additionally, EVs' contents and surface substance can be altered to improve their therapeutic efficacy in the clinic by boosting targeting potential and drug delivery effectiveness. EVs can regulate immune system function by affecting the tumor microenvironment, thereby inhibiting tumor progression. Co-delivery systems for EVs can be utilized to further improve the drug delivery efficiency of EVs, including hydrogels and liposomes. In this review, we discuss the isolation technologies of EVs, as well as engineering approaches to their modification. Moreover, we evaluate the therapeutic potential of EVs in tumors, including engineered extracellular vesicles and EVs' co-delivery systems.

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“…The EVs derived from mesenchymal stromal cells (MSCs) have been broadly investigated as in various drug delivery systems for cell-free therapy, possessing the natural ability of homing to BC tumor, low immunogenicity, and elastic properties ( Pinky et al, 2021 ). The EVs isolated from human umbilical cord mesenchymal stem cells (hUCMSCs) could upload cannabidiol (CBD) to increase the doxorubicin (DOX) sensitivity of MDA-MB-231 cells, leading to increased apoptosis expression and reduced tumor burden ( Patel et al, 2021 ). EV derived from adipose tissue-mesenchymal stromal cells (ADSCs), could mediate the transmission of miR-424-5p to inhibit the PD-L1/PD-1 signaling, thus conferring an inflammatory TME and enhancing immunotherapy ( Patel et al, 2021 ).…”

Section: Extracellular Vesicles In Triple-negative Breast Cancer Trea...mentioning

confidence: 99%

“…The EVs isolated from human umbilical cord mesenchymal stem cells (hUCMSCs) could upload cannabidiol (CBD) to increase the doxorubicin (DOX) sensitivity of MDA-MB-231 cells, leading to increased apoptosis expression and reduced tumor burden ( Patel et al, 2021 ). EV derived from adipose tissue-mesenchymal stromal cells (ADSCs), could mediate the transmission of miR-424-5p to inhibit the PD-L1/PD-1 signaling, thus conferring an inflammatory TME and enhancing immunotherapy ( Patel et al, 2021 ). Shojaei et al showed that the miR-381-carrying ADSC-exosomes could be internalized by MDA-MB-231 cells, resulting in inhibited proliferation, migration, and invasion by altering EMT-related gene expression ( Shojaei et al, 2021 ).…”

Section: Extracellular Vesicles In Triple-negative Breast Cancer Trea...mentioning

confidence: 99%

Extracellular Vesicles: The Landscape in the Progression, Diagnosis, and Treatment of Triple-Negative Breast Cancer

Dong

Liu

et al. 2022

Front. Cell Dev. Biol.

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Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer (BC) with diverse biological behavior, high aggressiveness, and poor prognosis. Extracellular vesicles (EVs) are nano-sized membrane-bound vesicles secreted by nearly all cells, and are involved in physiological and pathological processes. EVs deliver multiple functional cargos into the extracellular space, including proteins, lipids, mRNAs, non-coding RNAs (ncRNAs), and DNA fragments. Emerging evidence confirms that EVs enable pro-oncogenic secretome delivering and trafficking for long-distance cell-to-cell communication in shaping the tumor microenvironment (TME). The transferred tumor-derived EVs modify the capability of invasive behavior and organ-specific metastasis in recipient cells. In addition, TNBC cell-derived EVs have been extensively investigated due to their promising potential as valuable biomarkers for diagnosis, monitoring, and treatment evaluation. Here, the present review will discuss the recent progress of EVs in TNBC growth, metastasis, immune regulation, as well as the potential in TNBC diagnosis and treatment application, hoping to decipher the advantages and challenges of EVs for combating TNBC.

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Cannabidiol loaded extracellular vesicles sensitize triple-negative breast cancer to doxorubicin in both in-vitro and in vivo models

Cited by 34 publications

References 140 publications

Biophysical, Molecular and Proteomic profiling of Human Retinal Organoids derived Exosomes

Biophysical, Molecular and Proteomic profiling of Human Retinal Organoids derived Exosomes

Application of engineered extracellular vesicles for targeted tumor therapy

Extracellular Vesicles: The Landscape in the Progression, Diagnosis, and Treatment of Triple-Negative Breast Cancer

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