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Aptamers as Delivery Agents of siRNA and Chimeric Formulations for the Treatment of Cancer.

ABSTRACT: Both aptamers and siRNA technologies have now reached maturity, and both have been validated with a product in the market. However, although pegaptanib reached the market some time ago, there has been a slow process for new aptamers to follow. Today, some 40 aptamers are in the market, but many in combination with siRNAs, in the form of specific delivery agents. This combination offers the potential to explore the high affinity and specificity of aptamers, the silencing power of siRNA, and, at times, the cytotoxicity of chemotherapy molecules in powerful combinations that promise to delivery new and potent therapies. In this review, we report new developments in the field, following up from our previous work, more specifically on the use of aptamers as delivery agents of siRNA in nanoparticle formulations, alone or in combination with chemotherapy, for the treatment of cancer.

SUBMITTER: Dinis Ano Bom AP

PROVIDER: S-EPMC6956146 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Aptamers as Delivery Agents of siRNA and Chimeric Formulations for the Treatment of Cancer.

Dinis Ano Bom Ana Paula AP da Costa Neves Patrícia Cristina PC Bonacossa de Almeida Carlos Eduardo CE Silva Dilson D Missailidis Sotiris S

Pharmaceutics 20191216 12

Both aptamers and siRNA technologies have now reached maturity, and both have been validated with a product in the market. However, although pegaptanib reached the market some time ago, there has been a slow process for new aptamers to follow. Today, some 40 aptamers are in the market, but many in combination with siRNAs, in the form of specific delivery agents. This combination offers the potential to explore the high affinity and specificity of aptamers, the silencing power of siRNA, and, at t ...[more]

PMID: 31888119

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Project description:Small interfering RNA (siRNA)-based therapies have great promise in the treatment of a number of prevalent pulmonary disorders including lung cancer, asthma and cystic fibrosis. However, progress in this area has been hindered due to the lack of carriers that can efficiently deliver siRNA to lung epithelial cells, and also due to challenges in developing oral inhalation (OI) formulations for the regional administration of siRNA and their carriers to the lungs. In this work we report the ability of generation four, amine-terminated poly(amidoamine) (PAMAM) dendrimer (G4NH2)-siRNA complexes (dendriplexes) to silence the enhanced green fluorescent protein (eGFP) gene on A549 lung alveolar epithelial cells stably expressing eGFP. We also report the formulation of the dendriplexes and their aerosol characteristics in propellant-based portable OI devices. The size and gene silencing ability of the dendriplexes was seen not to be a strong function of the N/P ratio. Silencing efficiencies of up to 40% are reported. Stable dispersions of the dendriplexes encapsulated in mannitol and also in a biodegradable and water-soluble co-oligomer were prepared in hydrofluoroalkane (HFA)-based pressurized metered-dose inhalers (pMDIs). Their aerosol characteristics were very favorable, and conducive to deep lung deposition, with respirable fractions of up to 77%. Importantly, siRNA formulated as dendriplexes in pMDIs was shown to keep its integrity after the particle preparation processes, and also after long-term exposures to HFA. The relevance of this study stems from the fact that this is the first work to report the formulation of inhalable siRNA with aerosol properties suitable to deep lung deposition using pMDIs devices that are the least expensive and most widely used portable inhalers. This study is relevant because, also for the first time, it shows that siRNA-G4NH2 dendriplexes can efficiently target lung alveolar epithelial A549 cells and silence genes even after siRNA has been exposed to the propellant environment.

Dataset Information

Aptamers as Delivery Agents of siRNA and Chimeric Formulations for the Treatment of Cancer.

Publications

Aptamers as Delivery Agents of siRNA and Chimeric Formulations for the Treatment of Cancer.

Similar Datasets

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