Gemcitabine loaded autologous exosomes for effective and safe chemotherapy of pancreatic cancer

Li, Yong-Jiang; Wu, Jun-Yong; Wang, Jiemin; Hu, Xiong-Bin; Cai, Jiaxin; Xiang, Da‐Xiong

doi:10.1016/j.actbio.2019.10.022

Cited by 223 publications

(147 citation statements)

References 51 publications

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“…A total of 100 μl of cellular suspension containing 1×10 7 PANC-1 or BxPC-3 cells or shNrf2 PANC-1 or BxPC-3 cells were injected subcutaneously into the right hind limbs of the mice. When the tumours grew tõ 50 mm 3 , the mice were randomly divided into four groups (n = 5) following simple randomization procedures: control group, shNrf2 group, anlotinib group and shNrf2 combined with anlotinib group. Then, 4 mg/kg anlotinib 10,20 was infused into the mice in the anlotinib group and the co-treatment group by intragastric administration, and an equal volume of PBS was infused into the mice in the other two groups in the same manner.…”

Section: Xenograft Studiesmentioning

confidence: 99%

“…Despite progress in treatments, patients with PDAC respond poorly to chemotherapy, mainly due to drug resistance. First-line chemotherapy with gemcitabine 3 or the FORFIRINOX regime (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) 4 has only a 5.4% partial response rate in patients with PDAC. Hence, there is an urgent demand to enhance the treatment of this malignant cancer.…”

Section: Introductionmentioning

confidence: 99%

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Reactive oxygen species mediate anlotinib-induced apoptosis via activation of endoplasmic reticulum stress in pancreatic cancer

et al. 2020

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Anlotinib (AL3818), a novel multi-targeted receptor tyrosine kinase inhibitor, has recently been proven to be an antitumour drug. This study aimed to explore the antitumour effect of anlotinib and its underlying molecular mechanisms in human pancreatic cancer (PC) cells. The anti-proliferative effect of anlotinib for three PC cell lines was validated using CCK-8, colony formation and EdU detection assays. Cell cycle, cell apoptosis, and reactive oxygen species (ROS) detection assays, a PC xenograft model and immunohistochemistry were performed to elucidate the mechanisms by which anlotinib induced tumour lethality in vitro and in vivo. These results demonstrated that anlotinib inhibited proliferation, induced G2/M phase arrest and triggered apoptosis in PC cell lines. Anlotinib induced PC’s apoptosis through the accumulation of ROS which activated the endoplasmic reticulum (ER) stress via PERK/p-eIF2α/ATF4 pathway. Furthermore, we demonstrated that the expression level of Nrf2, an antioxidant protein, increased with anlotinib treatment. Nrf2 knockdown enhanced the pro-apoptotic effect of anlotinib and the expression of the PERK/p-eIF2α/ATF4 pathway. The in vivo results suggested that suppressing Nrf2 improved the antitumour effect of anlotinib on PC cells. These data indicated that the apoptotic effect of anlotinib on PC cells was induced by ER stress via the accumulation of ROS. In the future, anlotinib combined with an Nrf2 inhibitor may provide a new therapeutic strategy for the treatment of human PC.

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Section: Xenograft Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reactive oxygen species mediate anlotinib-induced apoptosis via activation of endoplasmic reticulum stress in pancreatic cancer

et al. 2020

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“…For example, PTX was loaded into sEVs more efficiently by sonication than electroporation and incubation [ 139 ]. However, the sonicating probe produces consistent heat during the sonication and the operation has to be done on ice, with intervals between strokes [ 153 ]. There is no doubt that sonication may compromise the membrane integrity of sEVs, with the therapeutics occasionally being attached to the outer membrane of the sEV, which affects the drug distribution in vivo [ 139 ].…”

Section: Evs As Drug Carriers In Cancer Treatmentmentioning

confidence: 99%

Extracellular Vesicles in the Development of Cancer Therapeutics

Sun

Burrola

et al. 2020

IJMS

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Extracellular vesicles (EVs) are small lipid bilayer-delimited nanoparticles released from all types of cells examined thus far. Several groups of EVs, including exosomes, microvesicles, and apoptotic bodies, have been identified according to their size and biogenesis. With extensive investigations on EVs over the last decade, it is now recognized that EVs play a pleiotropic role in various physiological processes as well as pathological conditions through mediating intercellular communication. Most notably, EVs have been shown to be involved in cancer initiation and progression and EV signaling in cancer are viewed as potential therapeutic targets. Furthermore, as membrane nanoparticles, EVs are natural products with some of them, such as tumor exosomes, possessing tumor homing propensity, thus leading to strategies utilizing EVs as drug carriers to effectively deliver cancer therapeutics. In this review, we summarize recent reports on exploring EVs signaling as potential therapeutic targets in cancer as well as on developing EVs as therapeutic delivery carriers for cancer therapy. Findings from preclinical studies are primarily discussed, with early phase clinical trials reviewed. We hope to provide readers updated information on the development of EVs as cancer therapeutic targets or therapeutic carriers.

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“…Before sEVs isolation, the supernatant from Panc-1 cells was handled as previously described 18 . Brie y, supernatant was centrifuged at 300 g for 10 min to remove cells, centrifuged at 2,000 g for 10 min to remove the dead cells, and then centrifuged at 10,000 g (Thermo Fisher ST 16R, USA) for 1 h to remove the cell debris and microvesicles 19 .…”

Section: Preparation Of Sevs-containing Mediummentioning

confidence: 99%

“…Generally, EV biomarker study demanded the purest EVs for exploring the relationship between EV and diseases 13,14 , and EV therapeutic study demanded pure and large quantities of EVs 15 . Pancreatic cancer-derived sEVs have shown potentials for early disease detection 16 and therapeutic application 17 .…”

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confidence: 99%

Comparative Evaluation of Methods for Isolating Small Extracellular Vesicles Derived from Pancreatic Cells

Wang

et al. 2020

Preprint

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Background: Small extracellular vesicles (sEVs) are nanosized vesicles involved in cell-to-cell communication. sEVs have been widely studied for clinical applications such as early detection of diseases and as therapeutics. Various methods for sEVs isolation have been using, but different methods may result in different qualities of sEVs and impact downstream analysis and applications. Here, we compared current isolation methods and performed a comparative analysis of sEVs derived from pancreatic cancer cells.Results: Ultracentrifugation, ultrafiltration and co-precipitation as concentration methods were firstly evaluated for yield, size, morphology and protein level of pellets. Then, isolate sEVs obtained by four different purification methods: size exclusion chromatography, density gradient ultracentrifugation, ultracentrifugation, and immunoaffinity capturing, were analysed and compared. For the concentration process, ultracentrifugation method obtained high quality and concentration pellets. For the purification process, immunoaffinity capturing method obtained the purest sEVs with less contaminants, while density gradient ultracentrifugation-based method obtained sEVs with the smallest size. Proteomic analysis revealed distinct protein contents of purified sEVs. Conclusions: For isolating sEVs derived from pancreatic cancer cells, ultracentrifugation-based method is recommended for concentration of sEVs, density gradient ultracentrifugation-based method may be suitable for isolation of sEVs for therapeutic study, immunoaffinity capturing may be applied for studies exploring sEVs as biomarkers.

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Gemcitabine loaded autologous exosomes for effective and safe chemotherapy of pancreatic cancer

Cited by 223 publications

References 51 publications

Reactive oxygen species mediate anlotinib-induced apoptosis via activation of endoplasmic reticulum stress in pancreatic cancer

Reactive oxygen species mediate anlotinib-induced apoptosis via activation of endoplasmic reticulum stress in pancreatic cancer

Extracellular Vesicles in the Development of Cancer Therapeutics

Comparative Evaluation of Methods for Isolating Small Extracellular Vesicles Derived from Pancreatic Cells

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