Transplantation of autologous extracellular vesicles for cancer-specific targeting

Villa, Alessandro; Garofalo, Mariangela; Crescenti, Daniela; Rizzi, Nicoletta; Brunialti, Electra; Vingiani, Andrea; Belotti, Paolo; Sposito, Carlo; Franzè, Silvia; Cilurzo, Francesco; Pruneri, Giancarlo; Recordati, Camilla; Giudice, Chiara; Giordano, Alessia; Tortoreto, Monica; Beretta, Giangiacomo; Stefanello, D.; Manenti, Giacomo; Zaffaroni, Nadia; Mazzaferro, Vincenzo; Ciana, Paolo

doi:10.7150/thno.51344

Cited by 39 publications

(38 citation statements)

References 41 publications

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“…The authors demonstrated that fluorescently labelled EVs from colorectal cancer patients, when injected in mice, selectively target patient-derived xenografts. Furthermore, their preliminary experiments performed in mast cells and mammary tumour-bearing dogs also showed tumour tropism of autologous plasma EVs that were fluorescently labelled [ 170 ]. These results not only show the participation of circulating EVs in tumour intercellular communication, but also open up interesting possibilities for human tumour detection and precision surgery.…”

Section: Potential Applications Of Extracellular Vesicles Introduced In Circulationmentioning

confidence: 99%

Extracellular Vesicles in Blood: Sources, Effects, and Applications

Alberro

Iparraguirre

Fernandes

et al. 2021

IJMS

105

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Extracellular vesicles (EVs) are important players for intercellular communication. EVs are secreted by almost all cell types; they can transfer information between nearby or distant cells, and they are highly abundant in body fluids. In this review, we describe the general characteristics of EVs, as well as isolation and characterization approaches. Then, we focus on one of the most relevant sources of EVs: the blood. Indeed, apart from EVs secreted by blood cells, EVs of diverse origins travel in the bloodstream. We present the numerous types of EVs that have been found in circulation. Besides, the implications of blood-derived EVs in both physiological and pathological processes are summarized, highlighting their potential as biomarkers for the diagnosis, treatment monitoring, and prognosis of several diseases, and also as indicators of physiological modifications. Finally, the applications of EVs introduced in the circulatory system are discussed. We describe the use of EVs from distinct origins, naturally produced or engineered, autologous, allogeneic, or even from different species and the effects they have when introduced in circulation. Therefore, the present work provides a comprehensive overview of the components, effects, and applications of EVs in blood.

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Section: Potential Applications Of Extracellular Vesicles Introduced In Circulationmentioning

confidence: 99%

Extracellular Vesicles in Blood: Sources, Effects, and Applications

Alberro

Iparraguirre

Fernandes

et al. 2021

IJMS

105

View full text Add to dashboard Cite

show abstract

“…While strong fluorescence signals of Lipo were observed in the liver, but Lipo showed less accumulation at the tumor site than MP-LP, demonstrating that the membrane protein modification enhanced the tumor-targeting effects of the nanoparticle. The autologous targeting or homing properties has been reported (Li et al, 2019 ; Villa et al, 2021 ). It might be difficult to specify the key protein or other components that mediate the targeting.…”

Section: Resultsmentioning

confidence: 99%

Membrane protein-chimeric liposome-mediated delivery of triptolide for targeted hepatocellular carcinoma therapy

et al. 2021

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Triptolide (TPL) is a diterpenoid triepoxide with broad antitumor efficacy, while lack of mechanism of action, severe systemic toxicity, and poor water solubility of TPL limited its usage. To unveil the mechanism of action and improve the pharmaceutical properties of TPL, here we explored the molecular mechanism of TPL and then fabricated TPL-loaded membrane protein-chimeric liposomes (TPL@MP-LP) and tested its anticancer efficacy against hepatocellular carcinoma (HCC). CCK8 assay, colony formation assay, EdU assay, and flow cytometry were used to examine the activity of TPL. RNA sequence and gain-and-loss of function assays were used to explore the molecular mechanisms. TPL@MP-LP was characterized by size, zeta potential, polydispersity index, and transmission electron microscopy. Cellular uptake and cell viability assay were performed to evaluate the internalization and anticancer efficacy of TPL@MP-LP in vitro . Biodistribution and in vivo antitumor efficacy of TPL@MP-LP were evaluated on orthotopic HCC mice models. TPL robustly inhibited HCC cells by inducing cell proliferation arrest, apoptosis via the mitochondrial pathway, and necroptosis via RIPK1/RIPK3/MLKL signaling. TPL was successfully loaded into MP-LP, with a drug-loading capacity of 5.62 ± 0.80%. MP-LP facilitated TPL internalization and TPL@MP-LP exerted enhanced anticancer efficacy against Huh7 cells. TPL@MP-LP showed targeting ability to the tumor site. More importantly, TPL@MP-LP treatment suppressed tumor growth but showed minimal damage to liver and renal functions. TPL exerted anticancer effects on HCC via inducing cell proliferation arrest, apoptosis, and necroptosis, and the MP-LP might be a promising delivery strategy to improve the antitumor efficacy while mitigating toxicity of TPL for HCC therapy.

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“…EVs can also convey RNAs, including mRNAs, miRNAs, and lncRNAs, which represent their cells of origin [ 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. Interestingly, EVs possess the capacity to transfer specific proteins and genetic materials to the recipient cells and, also, EV membranes can be engineered using organ-specific therapeutic proteins or drugs for treating the incurable disease of target organs [ 85 , 86 , 87 , 88 , 89 , 90 ]. Moreover, the application of EVs obviates the biosafety issues incurred by the direct application of whole stem cells, including tumorigenicity and immunogenic reactions [ 91 , 92 ].…”

Section: Discussionmentioning

confidence: 99%

High Therapeutic and Esthetic Properties of Extracellular Vesicles Produced from the Stem Cells and Their Spheroids Cultured from Ocular Surgery-Derived Waste Orbicularis Oculi Muscle Tissues

et al. 2021

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Extracellular vesicles (EVs) are paracrine factors that mediate stem cell therapeutics. We aimed at evaluating the possible therapeutic and esthetic applications of EVs prepared from the waste human facial tissue-derived orbicularis oculi muscle stem cells (OOM-SCs). OOM-SCs were isolated from the ocular tissues (from elders and youngsters) after upper eyelid blepharoplasty or epiblepharon surgeries. EVs were prepared from the OOM-SCs (OOM-SC-EVs) and their three-dimensional spheroids. OOM-SCs showed a spindle-like morphology with trilineage differentiation capacity, positive expression of CD105, CD 90, and CD73, and negative expression of CD45 and CD34, and their stem cell properties were compared with other adult mesenchymal stem cells. OOM-SC-EVs showed a high inhibitory effect on melanin synthesis in B16F10 cells by blocking tyrosinase activity. OOM-SC-EVs treatment led to a significant attenuation of senescence-associated changes, a decrease in reactive oxygen species generation, and an upregulation of antioxidant genes. We demonstrated the regeneration activity of OOM-SC-EVs in in vitro wound healing of normal human dermal fibroblasts and upregulation of anti-wrinkle-related genes and confirmed the therapeutic potential of OOM-SC-EVs in the healing of the in vivo wound model. Our study provides promising therapeutic and esthetic applications of OOM-SC-EVs, which can be obtained from the ocular surgery-derived waste human facial tissues.

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Transplantation of autologous extracellular vesicles for cancer-specific targeting

Cited by 39 publications

References 41 publications

Extracellular Vesicles in Blood: Sources, Effects, and Applications

Extracellular Vesicles in Blood: Sources, Effects, and Applications

Membrane protein-chimeric liposome-mediated delivery of triptolide for targeted hepatocellular carcinoma therapy

High Therapeutic and Esthetic Properties of Extracellular Vesicles Produced from the Stem Cells and Their Spheroids Cultured from Ocular Surgery-Derived Waste Orbicularis Oculi Muscle Tissues

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