Tumor cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs

Qiao, Li; Hu, Shiqi; Huang, Ke; Su, Teng; Li, Zhenhua; Vandergriff, Adam C.; Cores, Jhon; Dinh, Phuong‐Uyen; Allen, Tyler A.; Shen, Deliang; Liang, Hongxia; Li, Yongjun

doi:10.7150/thno.39434

Cited by 277 publications

(233 citation statements)

References 45 publications

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“…To date, different types of exosomes have been developed to deliver drugs to tumors; tumor cell-derived exosomes (TEx), adipose stem cell-derived exosomes (AEx), and epidermal cell-derived exosomes are among the most promising ones [ 13 – 17 ]. Exosomes from different cells have differential properties, and TEx have inherent tumor-targeting capabilities [ 18 ]. Additionally, various biomedical imaging modalities have been modified to trace exosomes.…”

Section: Introductionmentioning

confidence: 99%

Hydrophobic insertion-based engineering of tumor cell-derived exosomes for SPECT/NIRF imaging of colon cancer

et al. 2021

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Background Tumor cell-derived exosomes (TEx) have emerged as promising nanocarriers for drug delivery. Noninvasive multimodality imaging for tracing the in vivo trafficking of TEx may accelerate their clinical translation. In this study, we developed a TEx-based nanoprobe via hydrophobic insertion mechanism and evaluated its performance in dual single-photon emission computed tomography (SPECT) and near-infrared fluorescence (NIRF) imaging of colon cancer. Results TEx were successfully isolated from HCT116 supernatants, and their membrane vesicle structure was confirmed by TEM. The average hydrodynamic diameter and zeta potential of TEx were 110.87 ± 4.61 nm and –9.20 ± 0.41 mV, respectively. Confocal microscopy and flow cytometry findings confirmed the high tumor binding ability of TEx. The uptake rate of 99mTc-TEx-Cy7 by HCT116 cells increased over time, reaching 14.07 ± 1.31% at 6 h of co-incubation. NIRF and SPECT imaging indicated that the most appropriate imaging time was 18 h after the injection of 99mTc-TEx-Cy7 when the tumor uptake (1.46% ± 0.06% ID/g) and tumor-to-muscle ratio (8.22 ± 0.65) peaked. Compared with radiolabeled adipose stem cell derived exosomes (99mTc-AEx-Cy7), 99mTc-TEx-Cy7 exhibited a significantly higher tumor accumulation in tumor-bearing mice. Conclusion Hydrophobic insertion-based engineering of TEx may represent a promising approach to develop and label exosomes for use as nanoprobes in dual SPECT/NIRF imaging. Our findings confirmed that TEx has a higher tumor-targeting ability than AEx and highlight the potential usefulness of exosomes in biomedical applications.

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Section: Introductionmentioning

confidence: 99%

Hydrophobic insertion-based engineering of tumor cell-derived exosomes for SPECT/NIRF imaging of colon cancer

et al. 2021

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“…Taken together, we believe that tumor cell‐derived suicide gene exosomes, as well as suicide gene exosomes derived from MSCs, 11 may serve as a novel intracellular anti‐cancer drug overcoming resistance induction and avoiding unpleasant side effect of chemotherapy. Very recently, it was reported clear evidence that tumor cell‐derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs 29 . All in all, suicide gene exosomes open up a plethora of possibilities for modification of their features to improve their tumor targeting, as well as stability in an effort to become “off‐the‐shelf drugs.”…”

Section: Discussionmentioning

confidence: 99%

Intracellular prodrug gene therapy for cancer mediated by tumor cell suicide gene exosomes

Altanerova¹,

Jakubechova²,

Benejova³

et al. 2020

Intl Journal of Cancer

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Recently, we reported about exosomes possessing messenger RNA (mRNA) of suicide gene secreted from mesenchymal stem/stromal cells (MSCs) engineered to express the suicide gene-fused yeast cytosine deaminase::uracil phospho-ribosyltransferase (yCD::UPRT). The yCD::UPRT-MSC exosomes are internalized by tumor cells and intracellularly convert prodrug 5-fluorocytosine (5-FC) to cytotoxic drug 5-fluorouracil (5-FU). Human tumor cells with the potential to metastasize release exosomes involved in the creation of a premetastatic niche at the predicted organs. We found that cancer cells stably transduced with yCD::UPRT gene by retrovirus infection released exosomes acting similarly like yCD::UPRT-MSC exosomes. Different types of tumor cells were transduced with the yCD::UPRT gene. The homogenous cell population of yCD::UPRT-transduced tumor cells expressed the yCD::UPRT suicide gene and secreted continuously exosomes with suicide gene mRNA in their cargo. All tumor cell suicide gene exosomes upon internalization into the recipient tumor cells induced the cell death by intracellular conversion of 5-FC to 5-FU and to 5-FUMP in a dosedependent manner. Most of tumor cell-derived suicide gene exosomes were tumor tropic, in 5-FC presence they killed tumor cells but did not inhibit the growth of human skin fibroblast as well as DP-MSCs. Tumor cell-derived suicide gene exosomes home to their cells of origin and hold an exciting potential to become innovative specific therapy for tumors and potentially for metastases. K E Y W O R D S gene-directed enzyme prodrug therapy, intracellular therapy, suicide gene, tumor suicide gene exosomes 1 | INTRODUCTION Further progress in cancer therapy of aggressive tumors and metastases requires an innovative therapeutic modality. The main problem in an improvement of cancer patient survival lays in difficulty of a localized therapeutic attack and distant tumor cell metastasis. Tumor progression is enhanced by circulating tumor cells that disseminated away from the primary tumor and form metastases. The cells retain their original homing character and they possess the ability to re-home to the site of their origin. 1 In addition, standard chemoand radiotherapies do not attack slowly dividing or dormant cancer stem cells. 2,3 All cells in the body release extracellular vesicles

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“…Exosomal integrins reveal the metastatic sites of the primary tumor cells 2 . TDEs can be used to deliver cancer drugs because of their ability to home back to their origin 29 . Moreover, they contain antigens from the tumor which can be used to develop cancer vaccines 5 .…”

Section: Discussionmentioning

confidence: 99%

The role of tumor-derived exosomes in tumor immune escape: A concise review

et al. 2020

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Exosomes are small vesicles secreted by viable cells into the microenvironment. These vesicles bring various compositions, including lipids, RNAs and proteins, which carry information from producer cells to target cells. Cancer cells also produce exosomes, termed as tumor-derived exosomes (TDEs), which play important roles in immune modulation, angiogenesis and metastasis of tumors. This review summarizes the roles of TDEs in tumor immune escape mechanisms. TDEs affect all kinds of tumor-associated immune cells, including natural killer (NK) cells, dendritic cells (DCs), T and B lymphocytes, and myeloid-derived suppressor cells (MDSCs). Generally, TDEs suppress the immune system to promote tumor immune escape, thereby significantly contributing to tumorigenesis and metastasis.

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Tumor cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs

Cited by 277 publications

References 45 publications

Hydrophobic insertion-based engineering of tumor cell-derived exosomes for SPECT/NIRF imaging of colon cancer

Hydrophobic insertion-based engineering of tumor cell-derived exosomes for SPECT/NIRF imaging of colon cancer

Intracellular prodrug gene therapy for cancer mediated by tumor cell suicide gene exosomes

The role of tumor-derived exosomes in tumor immune escape: A concise review

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