Aptamer Chimeras for Therapeutic Delivery: The Challenging Perspectives

Esposito, Carla Lucia; Catuogno, Silvia; Condorelli, Gerolama; Ungaro, Paola; Franciscis, Vittorio de

doi:10.3390/genes9110529

Cited by 34 publications

(29 citation statements)

References 110 publications

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“…When compared with typical targeted molecules antibodies, aptamers have a number of advantages, such as high affinity for binding to target molecules, limited synthesis cost, no batch-to-batch variability, higher target potential ranging from ions to live cells, small sizes that allows them to penetrate tissues and non-immunogenic, which may facilitate long-term therapeutic efficacy and safety 21. Most noteworthy is that on account of geometrical conformational flexibility and synthesis dynamics, aptamers can be readily synthesized and chemically modified for various therapeutic applications 22. Thus, since the first RNA aptamer developed in 1992,23 aptamers have been extensively developed and used in clinical diagnostics, therapeutic agents and tissue engineering applications.…”

Section: Introductionmentioning

confidence: 99%

<p>Novel Aptamer-Functionalized Nanoparticles Enhances Bone Defect Repair By Improving Stem Cell Recruitment</p>

Wang¹,

Wu²,

Qiao³

et al. 2019

IJN

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BackgroundThe restoration and repair method in the clinic of delayed fracture healing and non-union after comminuted fractures are urgently needed to improve the prognosis of patients. The recruitment of endogenous stem cells has been considered a promising approach in bone defect repair.ProposeThe aim of this study was to generate a de novel MSCs aptamer and developed the first, feasible, economical, bio-compatible, and functional MSCs aptamer-directed nanoparticles without complex manufacture to recruit mesenchymal stem cells (MSCs) for bone defect regeneration.MethodsWhole-cell SELEX was used to generate a de novel MSCs aptamer. Flow cytometry was applied to assess the binding specificities, affinities and sorting abilities of the aptamers. Nano-Aptamer Ball (NAB) was constructed by NHS/EDC reaction. The diameter and zeta of NAB were assessed by dynamic light scattering. CCK8 assay was utilized to evaluate whether NAB could cause non-specific cytotoxicity and induce cell proliferation. To evaluate the bone repair capacity of NAB, histomorphological staining, alizarin red and micro X-ray were used to observe the repair degree of defect in vivo. ELISA was used to detect osteopontin (OPN), osteocalcin (BGP) by, and alkaline phosphatase (ALP) in peripheral blood.ResultsMSCs aptamer termed as HM69 could bind with MSCs with high specificity and Kd of 9.67 nM, while has minimal cross-reactivities to other negative cells. HM69 could capture MSCs with a purity of >89%. In vitro, NAB could bind and capture MSCs effectively, whereas did not cause obvious cytotoxicity. In vivo, serum OPN, BGP, and ALP levels in the NAB group of rats were increased at both 2 and 4 weeks, indicating the repair and osteogenesis generation. The healing of bone defects in the NAB group was significantly better than control groups, the defects became blurred, and local trabecular bone growth could be observed in X-ray. The organized hematoma and cell growth in the bone marrow of the NAB group were more vigorous in bone sections staining.ConclusionThese suggested that HM69 and HM69-functionalized nanoparticles NAB exhibited the ability to recruit MSCs both in vitro and in vivo and achieved a better outcome of bone defect repair in a rat model. The findings demonstrate a promising strategy of using aptamer-functionalized bio-nanoparticles for the restoration of bone defects via aptamer-introduced homing of MSCs.

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Section: Introductionmentioning

confidence: 99%

<p>Novel Aptamer-Functionalized Nanoparticles Enhances Bone Defect Repair By Improving Stem Cell Recruitment</p>

Wang¹,

Wu²,

Qiao³

et al. 2019

IJN

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“…It is well established that aptamers function as highly selective vehicles for therapeutic substances, such as noncoding RNAs (ncRNAs),16, 17, 18, 19 to a specific target cell. Because of the significant internalization of 40L and A40s by target cells, both represent good candidates for selective delivery of therapeutic molecules to GSCs.…”

Section: Resultsmentioning

confidence: 99%

The Discovery of RNA Aptamers that Selectively Bind Glioblastoma Stem Cells

Affinito

Quintavalle

Esposito³

et al. 2019

Molecular Therapy - Nucleic Acids

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Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. Despite progress in surgical and medical neuro-oncology, prognosis for GBM patients remains dismal, with a median survival of only 14-15 months. The modest benefit of conventional therapies is due to the presence of GBM stem cells (GSCs) that cause tumor relapse and chemoresistance and, therefore, that play a key role in GBM aggressiveness and recurrence. So far, strategies to identify and target GSCs have been unsuccessful. Thus, the development of an approach for GSC detection and targeting would be fundamental for improving the survival of GBM patients. Here, using the cell-systematic evolution of ligand by exponential (SELEX) methodology on human primary GSCs, we generated and characterized RNA aptamers that selectively bind GSCs versus undifferentiated GBM cells. We found that the shortened version of the aptamer 40L, which we have called A40s, costained with CD133-labeled cells in human GBM tissue, suggestive of an ability to specifically recognize GSCs in fixed human tissues. Of note, both 40L and A40s were rapidly internalized by cells, allowing for the delivery of the microRNA miR-34c and the anti-microRNA anti-miR-10b, demonstrating that these aptamers can serve as selective vehicles for therapeutics. In conclusion, the aptamers 40L and A40s can selectively target GSCs. Given the crucial role of GSCs in GBM recurrence and therapy resistance, these aptamers represent innovative drug delivery candidates with a great potential in the treatment of GBM.

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“…Aptamers have been used to direct therapeutic RNA molecules to target sites [ 75 ] ( Figure 2 C). In terms of specificity and affinity, they are highly comparable to antibodies but are smaller, have a higher stability, and are easier to generate [ 76 ].…”

Section: Delivery Of Rna Therapeuticsmentioning

confidence: 99%

Paving the Road for RNA Therapeutics

Dammes

Peer

2020

Trends in Pharmacological Sciences

163

152

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Therapeutic RNA molecules possess high potential for treating medical conditions if they can successfully reach the target cell upon administration. However, unmodified RNA molecules are rapidly degraded and cleared from the circulation. In addition, their large size and negative charge complicates their passing through the cell membrane. The difficulty of RNA therapy, therefore, lies in the efficient intracellular delivery of intact RNA molecules to the tissue of interest without inducing adverse effects. Here, we outline the recent developments in therapeutic RNA delivery and discuss the wide potential in manipulating the function of cells with RNAs. The focus is not only on the variety of delivery strategies but also on the versatile nature of RNA and its wide applicability. This wide applicability is especially interesting when considering the modular nature of nucleic acids. An optimal delivery vehicle, therefore, can facilitate numerous clinical applications of RNA.

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Aptamer Chimeras for Therapeutic Delivery: The Challenging Perspectives

Cited by 34 publications

References 110 publications

<p>Novel Aptamer-Functionalized Nanoparticles Enhances Bone Defect Repair By Improving Stem Cell Recruitment</p>

<p>Novel Aptamer-Functionalized Nanoparticles Enhances Bone Defect Repair By Improving Stem Cell Recruitment</p>

The Discovery of RNA Aptamers that Selectively Bind Glioblastoma Stem Cells

Paving the Road for RNA Therapeutics

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