Dataset Information

Exosome-Encased Nucleic Acid Scaffold Chemotherapeutic Agents for Superior Anti-Tumor and Anti-Angiogenesis Activity.

ABSTRACT: Extracellular vesicles (EVs), or exosomes, play a pivotal role in tumor growth and metastasis, such as in the case of Kaposi Sarcoma. By loading tumor-derived EVs with chemotherapeutic drugs, we noted that their pro-tumor/pro-angiogenic phenotype was converted into an anti-tumor phenotype in vivo. Drug concentration in EVs was significantly higher than in clinically approved liposome formulation, as retention was facilitated by the presence of miRNAs inside the natural EVs. This demonstrates a new mechanism by which to increase the payload capacity of nanoparticles. By exploiting the targeting preferences of tumor-derived EVs, chemotherapeutics can be directed to specifically poison the cells and the microenvironment that enables metastasis.

SUBMITTER: McNamara RP

PROVIDER: S-EPMC9026271 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Exosome-Encased Nucleic Acid Scaffold Chemotherapeutic Agents for Superior Anti-Tumor and Anti-Angiogenesis Activity.

McNamara Ryan P RP Eason Anthony B AB Zhou Yijun Y Bigi Rachele R Griffith Jack D JD Costantini Lindsey M LM Rudek Michelle A MA Anders Nicole M NM Damania Blossom A BA Dittmer Dirk P DP

ACS bio & med chem Au 20220120 2

Extracellular vesicles (EVs), or exosomes, play a pivotal role in tumor growth and metastasis, such as in the case of Kaposi Sarcoma. By loading tumor-derived EVs with chemotherapeutic drugs, we noted that their pro-tumor/pro-angiogenic phenotype was converted into an anti-tumor phenotype <i>in vivo</i>. Drug concentration in EVs was significantly higher than in clinically approved liposome formulation, as retention was facilitated by the presence of miRNAs inside the natural EVs. This demonstra ...[more]

PMID: 35480227

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Project description:Background: Pathological angiogenesis is the hallmark of many vision-threatening diseases. Anti-VEGF is a primary treatment with substantial beneficial effects. However, such agents require frequent intravitreal injections. Our previous work established a method for effectively modifying exosomes (EXOs) for loading therapeutic peptides. Here, we used this system to load the anti-angiogenic peptide KV11, aiming to establish an EXO-based therapy strategy to suppress neovascularization in the retina. Methods: Using an anchoring peptide, CP05, we linked KV11 to endothelial cell (EC) derived EXOs, yielding EXOKV11. We tested the delivery efficiency of EXOKV11 via two commonly used ocular injection methods: retro-orbital injection and intravitreal injection. Deploying an oxygen-induced retinopathy (OIR) model and a VEGF injection model, we tested the effects of EXOKV11 on neovascular formation, EC proliferation, and vascular permeability. In vitro experiments were used to test the mechanism and to analyze the effects of EXOKV11 on EC proliferation, migration, and sprouting. Results: By using the EXO loading system, KV11 was more efficiently delivered to the blood vessels of the mouse retina via retro-orbital injection. In both OIR model and VEGF injection model, EXOKV11 was more effective than KV11 alone in inhibiting neovascularization and vessel leakage. The therapeutic effect of retro-orbital injection of EXOKV11 was comparable to the intravitreal injection of VEGF-trap. Mechanistically, KV11 alone inhibited VEGF-downstream signaling, while EXOKV11 showed a stronger effect. Conclusions: We used EXOs as a carrier for intraocular delivery of KV11. We showed that KV11 itself has an anti-angiogenic effect through retro-orbital injection, but that this effect was greatly enhanced when delivered with EXOs. Thus, this system has the potential to treat proliferative retinopathy via retro-orbital injection which is a less invasive manner compared with intravitreal injection.

Dataset Information

Exosome-Encased Nucleic Acid Scaffold Chemotherapeutic Agents for Superior Anti-Tumor and Anti-Angiogenesis Activity.

Publications

Exosome-Encased Nucleic Acid Scaffold Chemotherapeutic Agents for Superior Anti-Tumor and Anti-Angiogenesis Activity.

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