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Treatment of breast cancer with autophagy inhibitory microRNAs carried by AGO2-conjugated nanoparticles.

ABSTRACT: Nanoparticle based gene delivery systems holds great promise. Superparamagnetic iron oxide nanoparticles (SPIONs) are being heavily investigated due to good biocompatibility and added diagnostic potential, rendering such nanoparticles theranostic. Yet, commonly used cationic coatings for efficient delivery of such anionic cargos, results in significant toxicity limiting translation of the technology to the clinic. Here, we describe a highly biocompatible, small and non-cationic SPION-based theranostic nanoparticles as novel gene therapy agents. We propose for the first-time, the usage of the microRNA machinery RISC complex component Argonaute 2 (AGO2) protein as a microRNA stabilizing agent and a delivery vehicle. In this study, AGO2 protein-conjugated, anti-HER2 antibody-linked and fluorophore-tagged SPION nanoparticles were developed (SP-AH nanoparticles) and used as a carrier for an autophagy inhibitory microRNA, MIR376B. These functionalized nanoparticles selectively delivered an effective amount of the microRNA into HER2-positive breast cancer cell lines in vitro and in a xenograft nude mice model of breast cancer in vivo, and successfully blocked autophagy. Furthermore, combination of the chemotherapy agent cisplatin with MIR376B-loaded SP-AH nanoparticles increased the efficacy of the anti-cancer treatment both in vitro in cells and in vivo in the nude mice. Therefore, we propose that AGO2 protein conjugated SPIONs are a new class of theranostic nanoparticles and can be efficiently used as innovative, non-cationic, non-toxic gene therapy tools for targeted therapy of cancer.

SUBMITTER: Unal O

PROVIDER: S-EPMC7189576 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Treatment of breast cancer with autophagy inhibitory microRNAs carried by AGO2-conjugated nanoparticles.

Unal Ozlem O Akkoc Yunus Y Kocak Muhammed M Nalbat Esra E Dogan-Ekici Asiye Isin AI Yagci Acar Havva H Gozuacik Devrim D

Journal of nanobiotechnology 20200428 1

Nanoparticle based gene delivery systems holds great promise. Superparamagnetic iron oxide nanoparticles (SPIONs) are being heavily investigated due to good biocompatibility and added diagnostic potential, rendering such nanoparticles theranostic. Yet, commonly used cationic coatings for efficient delivery of such anionic cargos, results in significant toxicity limiting translation of the technology to the clinic. Here, we describe a highly biocompatible, small and non-cationic SPION-based thera ...[more]

PMID: 32345308

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Project description:Interaction of nanomaterials with the mammalian cells remains to be poorly understood at the molecular level. Here we report the first synthesis of hybrid nanomaterial termed phage mimetic nanorods (PMN’s) inspired from filamentous bacteriophage present in nature. We emulate filamentous bacteriophage structure by combining two separate nanoscale entities, one functionalized gold nanorods and the other is coat proteins isolated from filamentous bacteriophage obtained through landscape phage screening. Utilizing biochemical interactions between a phage-derived protein and functionalized gold nanorods, we synthesized novel phage mimetic nanorods. The resulting nanovectors showed excellent multi functional properties including target specificity, imaging and photo destruction ability in a model SKBR-3 breast cancer cells. In addition, to gain insight into the molecular interactions involved during internalization of PMNs by SKBR-3 cells, we performed gene expression profiling of cells exposed to PMNs as compared with naive cells. We identified 70 upregulated and 26 downregulated genes responding to PMNs. Heparin binding internalization was identified as most plausible mechanisms of PMNs entry. Members of Major Histocompatibility complex I (MHC class I) were activated by PMNs, leading to enhanced lysosome and proteasome activity. Seven members of poorly annotated G antigen family (GAGE) of genes were upregulated, and may represent novel mechanism of PMNs entry recognition by cells. In summary, we present a versatile technique of PMNs production as any protein isolated from phage libraries selected against any in vitro and in vivo cells can be used as a source to synthesize PMN’s. This study also opens new avenues to understand the role of nanomaterials at the molecular level. Investigate the effect of phage mimetic nanorods onto SKBT-3 cells Two groups were compared, three biological replicates each. One group was control cells and the other was test.

Dataset Information

Treatment of breast cancer with autophagy inhibitory microRNAs carried by AGO2-conjugated nanoparticles.

Publications

Treatment of breast cancer with autophagy inhibitory microRNAs carried by AGO2-conjugated nanoparticles.

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