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Nanoparticle-Based Delivery of Tumor Suppressor microRNA for Cancer Therapy.

ABSTRACT: Improved understanding of microRNA expression and function in cancer has revealed a range of microRNAs that negatively regulate many oncogenic pathways, thus representing potent tumor suppressors. Therapeutic targeting of the expression of these microRNAs to the site of tumors and metastases provides a promising avenue for cancer therapy. To overcome challenges associated with microRNA degradation, transient expression and poor targeting, novel nanoparticles are being developed and employed to shield microRNAs for tumor-targeted delivery. This review focuses on studies describing a variety of both natural and synthetic nanoparticle delivery vehicles that have been engineered for tumor-targeted delivery of tumor suppressor microRNAs in vivo.

SUBMITTER: O'Neill CP

PROVIDER: S-EPMC7072816 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Nanoparticle-Based Delivery of Tumor Suppressor microRNA for Cancer Therapy.

O'Neill Clodagh P CP Dwyer Róisín M RM

Cells 20200224 2

Improved understanding of microRNA expression and function in cancer has revealed a range of microRNAs that negatively regulate many oncogenic pathways, thus representing potent tumor suppressors. Therapeutic targeting of the expression of these microRNAs to the site of tumors and metastases provides a promising avenue for cancer therapy. To overcome challenges associated with microRNA degradation, transient expression and poor targeting, novel nanoparticles are being developed and employed to s ...[more]

PMID: 32102476

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Project description:PurposeIn radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits.Methods and materialsHere we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy. The spacers are made of poly(lactic-co-glycolic) acid (PLGA) as matrix and are physically identical in size to the commercially available brachytherapy spacers (5 mm × 0.8 mm). The silica nanoparticles, 250 nm in diameter, were conjugated with near infrared fluorophore Cy7.5 as a model drug, and the INCeRT spacers were characterized in terms of size, morphology, and composition using different instrumentation techniques. The spacers were further doped with an anticancer drug, docetaxel. We evaluated the in vivo stability, biocompatibility, and biodegradation of these spacers in live mouse tissues.ResultsThe electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked by the use of optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue in contrast to the control Cy7.5-PLGA spacer, which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth in contrast to control mice over 16 days.ConclusionsThe imaging with the Cy7.5 spacer and therapeutic efficacy with docetaxel spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in a slow, sustained manner in conjunction with brachytherapy, in contrast to the rapid clearance of the drugs when administered systemically. The results demonstrate that these spacers with tailored release profiles have potential in improving the combined therapeutic efficacy of chemoradiation therapy.

Dataset Information

Nanoparticle-Based Delivery of Tumor Suppressor microRNA for Cancer Therapy.

Publications

Nanoparticle-Based Delivery of Tumor Suppressor microRNA for Cancer Therapy.

Similar Datasets

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