Delivery Of Aptamers Research Articles

Sequential Delivery of Aptamer and STING Agonist Shuttled by Graphene Oxide

Stimulator of interferon genes (STING) is a prospective target spot of immunological therapy. The development of STING is still in the preliminary stage and full of challenges. such as lack of tumor specificity, and high-dose-induced T-cell apoptosis. Herein, the STING agonists were selectively delivered and released in the tumor through an aptamer (Apt) modified graphene oxide (GO). The STING agonist was released controllably from GO on account of the acidic tumor microenvironment, and then binds specifically to the STING protein, aiming to active STING pathway and stimulate immunosuppressive factors secretion via phosphorylating TBK1 and IFN IRF3, and secreta high-level IL-6. The resulting immunotherapy exhibited significant inhibition of colorectal tumors, and the producing stimulus was sufficient to activate plentiful enough T-cells with adaptability to inhibit the growth and metastasis of tumors. This work helps to promote sustaining study on the targeted delivery of STING agonists and enhanced activation of the STING pathway, and the translation of novel understanding to clinical applications will enhance the efficiency of immunotherapy for cancer with STING agonists.

Bone marrow mesenchymal stem cells derived exosomal miRNAs can modulate diabetic bone-fat imbalance.

Diabetes mellitus is a chronic metabolic disease with systemic complications. Patient with diabetes have increased risks of bone fracture. Previous studies report that diabetes could affect bone metabolism, however, the underlying mechanism is still unclear. We isolated exosomes secreted by bone marrow mesenchymal stem cells of normal and diabetic mice and test their effects on osteogenesis and adipogenesis. Then we screened the differential microRNAs by high-throughput sequencing and explored the function of key microRNA in vitro and in vivo. We find that lower bone mass and higher marrow fat accumulation, also called bone-fat imbalance, exists in diabetic mouse model. Exosomes secreted by normal bone marrow mesenchymal stem cells (BMSCs-Exos) enhanced osteogenesis and suppressed adipogenesis, while these effects were diminished in diabetic BMSCs-Exos. miR-221, as one of the highly expressed miRNAs within diabetic BMSCs-Exos, showed abilities of suppressing osteogenesis and promoting adipogenesis both in vitro and in vivo. Elevation of miR-221 level in normal BMSCs-Exos impairs the ability of regulating osteogenesis and adipogenesis. Intriguingly, using the aptamer delivery system, delivery normal BMSCs-Exos specifically to BMSCs increased bone mass, reduced marrow fat accumulation, and promoted bone regeneration in diabetic mice. We demonstrate that BMSCs derived exosomal miR-221 is a key regulator of diabetic osteoporosis, which may represent a potential therapeutic target for diabetes-related skeletal disorders.

Zn-based physiometacomposite nanoparticles: distribution, tolerance, imaging, andantiviral and anticancer activity.

The aim of this study was toinvestigate the distribution, tolerance, and anticancerandantiviral activity of Zn-based physiometacomposites (PMCs).Manganese, iron, nickel and cobalt-doped ZnO, ZnS or ZnSe were synthesized. Cell uptake, distribution into 3D culture and mice, andbiochemical and chemotherapeutic activity were studied by fluorescence/bioluminescence, confocal microscopy, flow cytometry, viability, antitumor and virus titer assays.Luminescence and inductively coupled plasma mass spectrometry analysis showed that nanoparticle distribution was liver >spleen >kidney >lung >brain, without tissue or blood pathology. Photophysical characterization as ex vivo tissue probes and LL37 peptide, antisense oligomeror aptamer delivery targeting RAS/Ras binding domain (RBD) was investigated. Treatment at25μg/ml for48 h showed ≥98-99% cell viability, 3D organoid uptake, 3-log inhibition of β-Galactosidase and porcine reproductive respiratory virus infection. Data support the preclinical development of PMCs for imaging and delivery targeting cancer and infectious disease.

In situ bone regeneration with sequential delivery of aptamer and BMP2 from an ECM-based scaffold fabricated by cryogenic free-form extrusion

In situ tissue engineering is a powerful strategy for the treatment of bone defects. It could overcome the limitations of traditional bone tissue engineering, which typically involves extensive cell expansion steps, low cell survival rates upon transplantation, and a risk of immuno-rejection. Here, a porous scaffold polycaprolactone (PCL)/decellularized small intestine submucosa (SIS) was fabricated via cryogenic free-form extrusion, followed by surface modification with aptamer and PlGF-2123-144*-fused BMP2 (pBMP2). The two bioactive molecules were delivered sequentially. The aptamer Apt19s, which exhibited binding affinity to bone marrow-derived mesenchymal stem cells (BMSCs), was quickly released, facilitating the mobilization and recruitment of host BMSCs. BMP2 fused with a PlGF-2123-144 peptide, which showed “super-affinity” to the ECM matrix, was released in a slow and sustained manner, inducing BMSC osteogenic differentiation. In vitro results showed that the sequential release of PCL/SIS-pBMP2-Apt19s promoted cell migration, proliferation, alkaline phosphatase activity, and mRNA expression of osteogenesis-related genes. The in vivo results demonstrated that the sequential release system of PCL/SIS-pBMP2-Apt19s evidently increased bone formation in rat calvarial critical-sized defects compared to the sequential release system of PCL/SIS-BMP2-Apt19s. Thus, the novel delivery system shows potential as an ideal alternative for achieving cell-free scaffold-based bone regeneration in situ.

MicroRNA-29b Promotes Subchondral Bone Loss in TMJ Osteoarthritis

Abnormal subchondral bone remodeling plays important roles during osteoarthritis (OA) pathology. Recent studies show that bone marrow mesenchymal stem cells (BMSCs) in osteoarthritic subchondral bones exhibit a prominent pro-osteoclastic effect that contributes to abnormal subchondral bone remodeling; however, the pathologic mechanism remains unclear. In the present study, we used a mouse model with OA-like change in the temporomandibular joint (TMJ) induced by an experimentally unilateral anterior crossbite (UAC) and found that the level of microRNA-29b (miR-29b), but not miR-29a or miR-29c, was markedly lower in BMSCs from subchondral bones of UAC mice as compared with that from the sham control mice. With an intra-articular aptamer delivery system, BMSC-specific overexpression of miR-29b by aptamer-agomiR-29b rescued subchondral bone loss and osteoclast hyperfunction in UAC mice, as demonstrated by a significant increase in bone mineral density, bone volume fraction, trabecular thickness, and the gene expression of osteocalcin and Runx2 but decreased trabecular separation, osteoclast number and osteoclast surface/bone surface, and the gene expression of cathepsin K, Trap, Wnt5a, Rankl, and Rank as compared with those in the UAC mice treated by aptamer-NC (all P < 0.05). In addition, BMSC-specific inhibition of miR-29b by aptamer-antagomiR-29b exacerbated those responses in UAC mice. Notably, although it primarily affected miR-29b levels in the subchondral bone (but not in cartilage and synovium), BMSC-specific overexpression of miR-29b in UAC mice largely rescued OA-like cartilage degradation, including decreased chondrocyte density, cartilage thickness, and the percentage areas of proteoglycans and type II collagen, while BMSC-specific inhibition of miR-29b aggravated these characteristics of cartilage degradation in UAC mice. Moreover, we identified Wnt5a, but not Rankl or Sdf-1, as the direct target of miR-29b. The results of the present study indicate that miR-29b is a key regulator of the pro-osteoclastic effects of BMSCs in TMJ-OA subchondral bones and plays important roles in the TMJ-OA progression.

Selective anti-ErbB3 aptamer modified sorafenib microparticles: In vitro and in vivo toxicity assessment

The delivery of aptamer modified therapeutic moieties to specific tissue sites has become one of the major therapeutic choices to reduce the toxicity of inhibitory drugs. Bearing this in mind, the current study was designed using sorafenib (SFB) encapsulated microparticles (MP) prepared with biodegradable poly (D, L-lactic-co-glycolic acid) (PLGA) copolymer. The surfaces of these microparticles were modified with RNA aptamer having a binding affinity towards ErbB3 receptors. SFB-loaded MP (MPS) were prepared by o/w solvent evaporation method and the surface was coupled with the amino group of aptamer by EDC/NHS chemistry. Physiochemical investigations were done by dynamic light scattering, scanning electron microscopy and FTIR. In vitro apoptosis assay, cell viability assay and metastatic progression showed a significant decrease (p < 0.001) in vitro cell viability for MPS and MPS-Apt as compared to MP. The synergistic combination of SFB and aptamer also decreased the metastatic progression of cells for an extended period. Microparticles were also evaluated for in vivo toxicity in female BALB/c mice. It was evident that the presence of aptamer decreased the generalized toxicity of MPS-Apt, as measured by mean body weight loss and blood profiles, keeping all the blood formed elements level within acceptable limits. The histopathological investigations showed some necrotic and pyknotic bodies. In a similar fashion, liver function test and renal function tests showed pronounced effects of formulations on vital organs.

MiR‑483‑3p regulates osteogenic differentiation of bone marrow mesenchymal stem cells by targeting STAT1.

Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is regulated by a variety of intracellular regulatory factors including osterix, runt-related transcription factor 2 (RUNX2), bone morphogenetic proteins and transforming growth factorβ. Recent studies have shown that microRNAs (miRs) serve a crucial role in this process. In the present study, miR-483-3p levels were significantly increased during osteogenic differentiation of mouse and human BMSCs. Overexpression of miR-483-3p promoted osteogenic differentiation, whereas inhibition of miR-483-3p reversed these effects. miR-483-3p regulated osteogenic differentiation of BMSCs by targeting STAT1, and thus enhancing RUNX2 transcriptional activity and RUNX2 nuclear translocation. In vivo, overexpression of miR-483-3p using a BMSC-specific aptamer delivery system stimulated bone formation in aged mice. Therefore, the present study suggested that miR-483-3p promoted osteogenic differentiation of BMSCs by targeting STAT1, and miR-483-3 prepresent a potential therapeutic target for age-related bone loss.

Exosomal DNA Aptamer Targeting α-Synuclein Aggregates Reduced Neuropathological Deficits in a Mouse Parkinson’s Disease Model

The α-synuclein aggregates are the main component of Lewy bodies in Parkinson’s disease (PD) brain, and they showed immunotherapy could be employed to alleviate α-synuclein aggregate pathology in PD. Recently we have generated DNA aptamers that specifically recognize α-synuclein. In this study, we further investigated the in vivo effect of these aptamers on the neuropathological deficits associated with PD. For efficient delivery of the aptamers into the mouse brain, we employed modified exosomes with the neuron-specific rabies viral glycoprotein (RVG) peptide on the membrane surface. We demonstrated that the aptamers were efficiently packaged into the RVG-exosomes and delivered into neurons in vitro and in vivo. Functionally, the aptamer-loaded RVG-exosomes significantly reduced the α-synuclein preformed fibril (PFF)-induced pathological aggregates, and rescued synaptic protein loss and neuronal death. Moreover, intraperitoneal administration of these exosomes into the mice with intra-striatally injected α-synuclein PFF reduced the pathological α-synuclein aggregates and improved motor impairments. In conclusion, we demonstrated that the aptamers targeting α-synuclein aggregates could be effectively delivered into the mouse brain by the RVG-exosomes and reduce the neuropathological and behavioral deficits in the mouse PD model. This study highlights the therapeutic potential of the RVG-exosome delivery of aptamer to alleviate the brain α-synuclein pathology.

Delivery of Cell-Specific Aptamers to the Arterial Wall with an Occlusion Perfusion Catheter

Current strategies to prevent restenosis following endovascular treatment include the local delivery of anti-proliferative agents to inhibit vascular smooth muscle cell (VSMC) proliferation and migration. These agents, not specific to VSMCs, are deposited on the luminal surface and therefore target endothelial cells and delay vascular healing. Cell-targeted therapies, (e.g., RNA aptamers), can potentially overcome these safety concerns by specifically binding to VSMC and inhibiting proliferation and migration. The purpose of this study was to therefore demonstrate the ability of a perfusion catheter to deliver cell-specific RNA aptamer inhibitors directly to the vessel wall. RNA aptamers specific to VSMCs were developed using an in vitro cell-based systematic evolution of ligand by exponential enrichment selection process. Two aptamers (Apt01 and Apt14) were evaluated ex vivo using harvested pig arteries in a pulsatile flow bioreactor. Local drug delivery of the aptamers into the medial wall was accomplished using a novel perfusion catheter. We demonstrated the feasibility to deliver aptamer-based drugs directly to the medial layer of an artery using a perfusion catheter. Such cell-specific targeted therapeutic drugs provide a potentially safer and more effective treatment option for patients with vascular disease.

In Vivo Use of a Multi-DNA Aptamer-Based Payload/Targeting System To Study Dopamine Dysregulation in the Central Nervous System.

The delivery of therapeutics across the blood-brain barrier remains a considerable challenge in investigating central nervous system related processes. In this work, a liposome vehicle was surface-modified with an aptamer that binds to the transferrin receptor and was loaded with two different dopamine-binding aptamer payloads. This system was effectively used to promote the delivery of the aptamer cargo from the peripheral injection site into the brain. The effect of these delivered aptamers on behavior was investigated in vivo in a locomotor task. The first dopamine binding aptamer assessed was a DNA aptamer, the binding of which had been previously validated through the aptamer-based biosensor development reported by several independent research groups. The second aptamer investigated was the result of a novel in vitro selection experiment described herein. Our data suggest that systemic administration of the modified liposomes led to delivery of the dopamine aptamers into the brain. Fluorescence microscopy revealed differential distribution of fluorescence based on the presence or absence of the transferrin receptor aptamer on the surface of fluorescently modified liposomes. In a behavioral experiment using cocaine administration to induce elevated concentrations of neural dopamine, systemic pretreatment with the dopamine aptamer-loaded liposomes reduced cocaine-induced hyperlocomotion. Multiple controls including a transferrin-negative liposome control and transferrin-positive liposomes loaded with either a nonbinding, base-substituted dopamine aptamer or a random oligonucleotide were investigated. None of these controls altered cocaine-induced hyperlocomotion. Chronic systemic administration of the modified liposomes produced no deleterious neurobehavioral or neural degenerative effects. Importantly, this work is one example of an application for this versatile multiaptamer payload/targeting system. Its general application is limited only by the availability of aptamers for specific neural targets.

A Novel Magnetic Carbon Nanotubes Functionalized with Pyridine Groups: Synthesis, Characterization and Their Application as an Efficient Carrier for Plasmid DNA and Aptamer

AbstractMagnetic functionalized multi‐walled carbon nanotubes have been synthesized, characterized and studied for therapeutically active nucleic acids interaction and delivery. In this study, pyridine functionalized magnetically was investigated for plasmid DNA and aptamer delivery. A thorough structural characterization of new carrierhas been carried out by means of transmission electron microscopy, scanning electron microscopy images, carbon, hydrogen and nitrogen elemental analysis, thermogravimetric analysis, vibrating‐sample magnetometer and spectroscopy. The magnetic properties of magnetic functionalized multi‐walled carbon nanotubes allow the directional control of conjugated nucleic acids with a transporter using an external magnetic field. They can be used as a transporter to afford noncovalent binding with nucleic acids and are supposed to cross the plasma membrane and internalize into the cytoplasm without inducing cell death.

Polymer Microneedle Mediated Local Aptamer Delivery for Blocking the Function of Vascular Endothelial Growth Factor.

Overexpression of proteins in the body can cause severe diseases and other physiological disturbances. The development of protein blockers and local delivery systems would offer opportunities for addressing the health problems caused by protein overexpression. Nucleic acid aptamers are an emerging class of ligands with the potential to block proteins effectively; however, little effort has been made in developing polymer systems for local aptamer delivery. In this work, polymer microneedles capable of delivering DNA aptamers locally to inhibit the function of vascular endothelial growth factor (VEGF) were developed and studied. The presence of anti-VEGF aptamer in the polymer matrix did not change the apparent mechanical strength of the microneedles. Once in contact with a physiological solution, the polymer microneedles quickly dissolved, generating a high concentration of anti-VEGF aptamer in the surrounding local microenvironment. Aptamer delivery by way of dissolving polymer microneedles in a tissue phantom reduced VEGF-mediated endothelial cell tube formation. Thus, aptamer-loaded polymer microneedles hold great potential as a therapeutic tool for the treatment of human diseases resulting from protein overexpression.

RNA Aptamer Delivery through Intact Human Skin

It is generally recognized that only relatively small molecular weight (typically < ∼ 500 Da) drugs can effectively permeate through intact stratum corneum. Here, we challenge this orthodoxy using a 62-nucleotide (molecular weight= 20,395 Da) RNA-based aptamer, highly specific to the human IL-23 cytokine, with picomolar activity. Results demonstrate penetration of the aptamer into freshly excised human skin using two different fluorescent labels. A dual hybridization assay quantified aptamer from the epidermis and dermis, giving levels far exceeding the cellular half maximal inhibitory concentration values (>100,000-fold), and aptamer integrity was confirmed using an oligonucleotide precipitation assay. A T helper 17 response was stimulated in freshly excised human skin resulting in significantly upregulated IL-17f, and IL-22; topical application of the IL-23 aptamer decreased both IL-17f and IL-22 by approximately 45% but did not result in significant changes to IL-23 mRNA levels, confirming that the aptamer did not globally suppress mRNA levels. This study demonstrates that very-large-molecular-weight RNA aptamers can permeate across the intact human skin barrier to therapeutically relevant levels into both the epidermis and dermis and that the skin-penetrating aptamer retains its biologically active conformational structure capable of binding to endogenous IL-23.

Site-selective conjugation of an anticoagulant aptamer to recombinant albumins and maintenance of neonatal Fc receptor binding

Aptamers are an attractive molecular medicine that offers high target specificity. Nucleic acid-based aptamers, however, are prone to nuclease degradation and rapid renal excretion that require blood circulatory half-life extension enabling technologies. The long circulatory half-life, predominately facilitated by engagement with the cellular recycling neonatal Fc receptor (FcRn), and ligand transport properties of albumin promote it as an attractive candidate to improve the pharmacokinetic profile of aptamers. This study investigates the effect of Cys34 site-selective covalent attachment of a factor IXa anticoagulant aptamer on aptamer functionality and human FcRn (hFcRn) engagement using recombinant human albumin (rHA) of either a wild type (WT) or an engineered human FcRn high binding variant (HB). Albumin-aptamer conjugates, connected covalently through a heterobifunctional succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate linker, were successfully prepared and purified by high performance liquid chromatography as confirmed by gel electrophoresis band-shift analysis and matrix-assisted laser desorption/ionization time of flight. Minimal reduction (∼25%) in activity of WT-linked aptamer to that of aptamer alone was found using an anticoagulant activity assay measuring temporal levels of activated partial thrombin. Covalent albumin-aptamer conjugation, however, substantially compromized binding to hFcRn, to 10% affinity of that of non-conjugated WT, determined by biolayer interferometry. Binding could be rescued by aptamer conjugation to recombinant albumin engineered for higher FcRn affinity (HB) that exhibited an 8-fold affinity compared to WT alone. This work describes a novel albumin-based aptamer delivery system whose hFcRn binding can be increased using a HB engineered albumin.

Applications of Aptamers in Medicine: A Mini Review

Aptamers are single-stranded DNA or RNA molecules that bind to its target with high affinity and specificity. Nucleic acid aptamers are an attractive class of carrier molecules because of their tissue penetration capability, high chemical flexibility, low immunogenicity, low toxicity and cost effective production. These characteristics make aptamers an alternative to the antibody. An aptamer can be developed for the treatment of age-related macular degeneracy disease, blood clotting, cancer and auto-immune diseases etc. Macugen is so far the only aptamer-based drug that received FDA approval. Cancer patients are treated by targeting two proteins named nucleolin and CXCL12. Targeted delivery of aptamers has been successfully developed that reduce the occurrence of the unwanted off-target effects. Aptamers are susceptible to renal filtration and endonuclease cleavage. Conjugation with PEG or cholesterol and chemical modification can decrease renal clearance and increase serum stability.Bangladesh Pharmaceutical Journal 20(1): 99-104, 2017

Aptamer delivery of siRNA, radiopharmaceutics and chemotherapy agents in cancer

Aptamers are oligonucleotide reagents with high affinity and specificity, which among other therapeutic and diagnostic applications have the capability of acting as delivery agents. Thus, aptamers are capable of carrying small molecules, nanoparticles, radiopharmaceuticals or fluorescent agents as well as nucleic acid therapeutics specifically to their target cells. In most cases, the molecules may possess interesting therapeutic properties, but their lack of specificity for a particular cell type, or ability to internalise in such a cell, hinders their clinical development, or cause unwanted side effects. Thus, chemotherapy or radiotherapy agents, famous for their side effects, can be coupled to aptamers for specific delivery. Equally, siRNA have great therapeutic potential and specificity, but one of their shortcomings remain the delivery and internalisation into cells. Various methodologies have been proposed to date, including aptamers, to resolve this problem. Therapeutic or imaging reagents benefit from the adaptability and ease of chemical manipulation of aptamers, their high affinity for the specific marker of a cell type, and their internalisation ability via cell mediated endocytosis. In this review paper, we explore the potential of the aptamers as delivery agents and offer an update on current status and latest advancements.

Design and Preparation of Aptamer-siRNA Chimeras (AsiCs) for Targeted Cancer Therapy.

Conjugation of cell-internalizing DNA or RNA aptamers to tumor-suppressing siRNAs represents a novel promising approach for cancer therapy. Here we describe how to employ RNA aptamers that bind to cell surface receptors as carriers for cell-targeted siRNA (or miRNA) delivery. This protocol was optimized to improve the efficiency of the aptamer-siRNA/miRNA conjugates and facilitate its implementation in most molecular biology labs. The single working steps include (1) outlining the optimal sequences of the RNA strands bearing the aptamer and siRNA sequence, for which further (2) a dsDNA template is synthesized and then (3) transcribed into an RNA that will be (4) folded and annealed to a chemically synthesized siRNA complementary strand. Moreover, we reference recent examples and advances in the aptamer delivery field.

Method for Confirming Cytoplasmic Delivery of RNA Aptamers.

RNA aptamers are single-stranded RNA oligos that represent a powerful emerging technology with potential for treating numerous diseases. More recently, cell-targeted RNA aptamers have been developed for delivering RNA interference (RNAi) modulators (siRNAs and miRNAs) to specific diseased cells (e.g., cancer cells or HIV infected cells) in vitro and in vivo. However, despite initial promising reports, the broad application of this aptamer delivery technology awaits the development of methods that can verify and confirm delivery of aptamers to the cytoplasm of target cells where the RNAi machinery resides. We recently developed a functional assay (RIP assay) to confirm cellular uptake and subsequent cytoplasmic release of an RNA aptamer which binds to a cell surface receptor expressed on prostate cancer cells (PSMA). To assess cytoplasmic delivery, the aptamer was chemically conjugated to saporin, a ribosome inactivating protein toxin that is toxic to cells only when delivered to the cytoplasm (where it inhibits the ribosome) by a cell-targeting ligand (e.g., aptamer). Here, we describe the chemistry used to conjugate the aptamer to saporin and discuss a gel-based method to verify conjugation efficiency. We also detail an in vitro functional assay to confirm that the aptamer retains function following conjugation to saporin and describe a cellular assay to measure aptamer-mediated saporin-induced cytotoxicity.

Investigation on novel chitosan nanoparticle–aptamer complexes targeting TGF-β receptor II

In our previous study, a dominant sequence called aptamer S58 antagonized TGF-β-induced myofibroblast transdifferentiation in human Tenon's capsule fibroblasts (HTFs) through sealing the targeting site of TGF-β receptor II (TβR II). However, rapid degradation by ubiquitous nucleases limited the aptamer's efficacy. Chitosan-nanoparticles (CS-NP) are good drug carriers. Herein we synthesises novel chitosan nanoparticle-aptamer S58 complexes called CS(S58)-NP in order to preserve and prolong S58's efficacy. We synthesised CS(S58)-NP at various molar ratios of CS-NP to S58 using an ionic gelation method. Then, the properties of the CS(S58)-NP including particle size, zeta potential, protection capacity, slow-release effect and cytotoxicity were studied. The targeting effect of the CS(S58)-NP was also studied. CS(S58)-NP at molar ratios of 20 and 30 showed high aptamer encapsulation efficiency, powerful aptamer protection, stable sustained-release ability and low cytotoxicity. FITC-labelled CS(S58)-NP could successfully bind to TβR II. As a result, TGF-β-induced cell proliferation and α-SMA expression were both inhibited. Furthermore, the CS(S58)-NP could inhibit TGF-β-induced α-SMA expression for a longer time than naked S58, even in serum. This research applied CS-NP as the aptamer carrier. The research results demonstrate that CS-NP are potentially able to preserve and prolong aptamer S58's efficacy. This study reveals that the use of CS-NP is promising for aptamer delivery and CS(S58)-NP can be a potential anti-scarring therapeutic approach after glaucoma filtration surgery.

RNA nanoparticles come of age

RNA nanoparticles come of age