Aptamer-Based Targeting of Cancer: A Powerful Tool for Diagnostic and Therapeutic Aims.

Cancer is known as one of the most significant causes of death worldwide, and, in spite of novel therapeutic methods, continues to cause a considerable number of deaths. Targeted molecular diagnosis and therapy using aptamers with high affinity have become popular techniques for pathological angiogenesis and cancer therapy scientists. In this paper, several aptamer-based diagnostic and therapeutic techniques such as aptamer-nanomaterial conjugation, aptamer-drug conjugation (physically or covalently), and biosensors, which have been successfully designed for biomarkers, were critically reviewed. The results demonstrated that aptamers can potentially be incorporated with targeted delivery systems and biosensors for the detection of biomarkers expressed by cancer cells. Aptamer-based therapeutic and diagnostic methods, representing the main field of medical sciences, possess high potential for use in cancer therapy, pathological angiogenesis, and improvement of community health. The clinical use of aptamers is limited due to target impurities, inaccuracy in the systematic evolution of ligands via exponential enrichment (SELEX)stage process, and in vitro synthesis, making them unreliable and leading to lower selectivity for in vivo targets. Moreover, size, behavior, probable toxicity, low distribution, and the unpredictable behavior of nanomaterials in in vivo media make their usage in clinical assays critical. This review is helpful for the implementation of aptamer-based therapies which are effective and applicable for clinical use and the design of future studies.

Next-generation therapeutics for rare genetic disorders.

The therapeutic potential of the human genome has been explored through the development of next-generation therapeutics, which have had a high impact on treating genetic disorders. Classical treatments have traditionally focused on common diseases that require repeated treatments. However, with the recent advancements in the development of nucleic acids, utilizing DNA and RNA to modify or correct gene expression in genetic disorders, there has been a paradigm shift in the treatment of rare diseases, offering more potential one-time cure options. Advanced technologies that use CRISPR-Cas 9, antisense oligonucleotides, siRNA, miRNA, and aptamers are promising tools that have achieved successful breakthroughs in the treatment of various genetic disorders. The advancement in the chemistry of these molecules has improved their efficacy, reduced toxicity, and expanded their clinical use across a wide range of tissues in various categories of human disorders. However, challenges persist regarding the safety and efficacy of these advanced technologies in translating into clinical practice. This review mainly focuses on the potential therapies for rare genetic diseases and considers how next-generation techniques enable drug development to achieve long-lasting curative effects through gene inhibition, replacement, and editing.

RNA therapeutics in cancer treatment.

RNA therapeutics are a class of drugs that use RNA molecules to treat diseases, including cancer. RNA therapeutics work by targeting specific genes or proteins involved in the disease process, with the aim of blocking or altering their activity to ultimately halt or reverse the disease progression. The use of RNA therapeutics in cancer treatment has shown great potential, as they offer the ability to specifically target cancer cells while leaving healthy cells intact. This is in contrast to traditional chemotherapy and radiation treatments, which can damage healthy cells and cause unpleasant side effects. The field of RNA therapeutics is rapidly advancing, with several types of RNA molecules being developed for cancer treatment, including small interfering RNA, microRNA, mRNA, and RNA aptamers. Each type of RNA molecule has unique properties and mechanisms of action, allowing for targeted and personalized cancer treatments. In this chapter, we will explore the different types of RNA therapeutics used in cancer treatment, their mechanisms of action, and their potential applications in treating different types of cancer. We will also discuss the challenges and opportunities in the development and research of RNA therapeutics for cancer, as well as the future outlook for this promising field.

Targeting vimentin: a multifaceted approach to combatting cancer metastasis and drug resistance.

This comprehensive review explores vimentin as a pivotal therapeutic target in cancer treatment, with a primary focus on mitigating metastasis and overcoming drug resistance. Vimentin, a key player in cancer progression, is intricately involved in processes such as epithelial-to-mesenchymal transition (EMT) and resistance mechanisms to standard cancer therapies. The review delves into diverse vimentin inhibition strategies. Precision tools, including antibodies and nanobodies, selectively neutralize vimentin's pro-tumorigenic effects. DNA and RNA aptamers disrupt vimentin-associated signaling pathways through their adaptable binding properties. Innovative approaches, such as vimentin-targeted vaccines and microRNAs (miRNAs), harness the immune system and post-transcriptional regulation to combat vimentin-expressing cancer cells. By dissecting vimentin inhibition strategies across these categories, this review provides a comprehensive overview of anti-vimentin therapeutics in cancer treatment. It underscores the growing recognition of vimentin as a pivotal therapeutic target in cancer and presents a diverse array of inhibitors, including antibodies, nanobodies, DNA and RNA aptamers, vaccines, and miRNAs. These multifaceted approaches hold substantial promise for tackling metastasis and overcoming drug resistance, collectively presenting new avenues for enhanced cancer therapy.

Aptamers in neuro-oncology: An emerging therapeutic modality.

Despite recent advances in the understanding of brain tumor pathophysiology, challenges associated with tumor location and characteristics have prevented significant improvement in neuro-oncology therapies. Aptamers are short, single-stranded DNA or RNA oligonucleotides that fold into sequence-specific, 3-dimensional shapes that, like protein antibodies, interact with targeted ligands with high affinity and specificity. Aptamer technology has recently been applied to neuro-oncology as a potential approach to innovative therapy. Preclinical research has demonstrated the ability of aptamers to overcome some obstacles that have traditionally rendered neuro-oncology therapies ineffective. Potential aptamer advantages include their small size, ability in some cases to penetrate the blood-brain barrier, inherent lack of immunogenicity, and applicability for discovering novel biomarkers. Herein, we review recent reports of aptamer applications in neuro-oncology including aptamers found by cell- and in vivo- Systematic Evolution of Ligands by Exponential Enrichment approaches, aptamer-targeted therapeutic delivery modalities, and aptamers in diagnostics and imaging. We further identify crucial future directions for the field that will be important to advance aptamer-based drugs or tools to clinical application in neuro-oncology.

Advances in screening, synthesis, modification, and biomedical applications of peptides and peptide aptamers.

Peptides and peptide aptamers have emerged as promising molecules for a wide range of biomedical applications due to their unique properties and versatile functionalities. The screening strategies for identifying peptides and peptide aptamers with desired properties are discussed, including high-throughput screening, display screening technology, and in silico design approaches. The synthesis methods for the efficient production of peptides and peptide aptamers, such as solid-phase peptide synthesis and biosynthesis technology, are described, along with their advantages and limitations. Moreover, various modification techniques are explored to enhance the stability, specificity, and pharmacokinetic properties of peptides and peptide aptamers. This includes chemical modifications, enzymatic modifications, biomodifications, genetic engineering modifications, and physical modifications. Furthermore, the review highlights the diverse biomedical applications of peptides and peptide aptamers, including targeted drug delivery, diagnostics, and therapeutic. This review provides valuable insights into the advancements in screening, synthesis, modification, and biomedical applications of peptides and peptide aptamers. A comprehensive understanding of these aspects will aid researchers in the development of novel peptide-based therapeutics and diagnostic tools for various biomedical challenges.

Discovery of Aptamers and the Acceleration of the Development of Targeting Research in Ophthalmology.

Aptamers are widely applied to diagnosis and therapy because of their targeting. However, the current progress of research into aptamers for the treatment of eye disorders has not been well-documented. The current literature on aptamers was reviewed in this study. Aptamer-related drugs and biochemical sensors have been evaluated for several eye disorders within the past decade; S58 targeting TGF-ß receptor II and pegaptanib targeting vascular endothelial growth factor (VEGF) are used to prevent fibrosis after glaucoma filtration surgery. Anti-brain-derived neurotrophic factor aptamer has been used to diagnose glaucoma. The first approved aptamer drug (pegaptanib) has been used to inhibit angiogenesis in age-related macular degeneration (AMD) and diabetic retinopathy (DR), and its efficacy and safety have been demonstrated in clinical trials. Aptamers, including E10030, RBM-007, AS1411, and avacincaptad pegol, targeting other angiogenesis-related biomarkers have also been discovered and subjected to clinical trials. Aptamers, such as C promoter binding factor 1, CD44, and advanced end products in AMD and DR, targeting other signal pathway proteins have also been discovered for therapy, and biochemical sensors for early diagnosis have been developed based on aptamers targeting VEGF, connective tissue growth factor, and lipocalin 1. Aptamers used for early detection and treatment of ocular tumors were derived from other disease biomarkers, such as CD71, nucleolin, and high mobility group A. In this review, the development and application of aptamers in eye disorders in recent years are systematically discussed, which may inspire a new link between aptamers and eye disorders. The aptamer development trajectory also facilitates the discovery of the pathogenesis and therapeutic strategies for various eye disorders.

Fulfilling the Promise of RNA Therapies for Cardiac Repair and Regeneration.

The progressive appreciation that multiple types of RNAs regulate virtually all aspects of tissue function and the availability of effective tools to deliver RNAs in vivo now offers unprecedented possibilities for obtaining RNA-based therapeutics. For the heart, RNA therapies can be developed that stimulate endogenous repair after cardiac damage. Applications in this area include acute cardioprotection after ischemia or cancer chemotherapy, therapeutic angiogenesis to promote new blood vessel formation, regeneration to form new cardiac mass, and editing of mutations to cure inherited cardiac disease. While the potential of RNA therapeutics for all these conditions is exciting, the field is still in its infancy. A number of roadblocks need to be overcome for RNA therapies to become effective, in particular, related to the problem of delivering RNA medicines into the cells and targeting them specifically to the heart.

Emerging Progress of RNA-Based Antitumor Therapeutics.

RNA-based therapeutics (e.g., mRNAs, siRNAs, microRNAs, ASOs, and saRNAs) have considerable potential for tumor treatment. The development and optimization of RNA modifications and delivery systems enable the stable and efficient delivery of RNA cargos in vivo to elicit an antitumor response. Targeted RNA-based therapeutics with multiple specificities and high efficacies are now available. In this review, we discuss progress in RNA-based antitumor therapeutics, including mRNAs, siRNAs, miRNAs, ASOs, saRNAs, RNA aptamers, and CRISPR-based gene editing. We focus on the immunogenicity, stability, translation efficiency, and delivery of RNA drugs, and summarize their optimization and the development of delivery systems. In addition, we describe the mechanisms by which RNA-based therapeutics induce antitumor responses. Furthermore, we review the merits and limitations of RNA cargos and their therapeutic potential for cancers.

Identification and characterization of aptameric inhibitors of human neutrophil elastase.

Human neutrophil elastase (HNE) plays a pivotal role in innate immunity, inflammation, and tissue remodeling. Aberrant proteolytic activity of HNE contributes to organ destruction in various chronic inflammatory diseases including emphysema, asthma, and cystic fibrosis. Therefore, elastase inhibitors could alleviate the progression of these disorders. Here, we used the systematic evolution of ligands by exponential enrichment to develop ssDNA aptamers that specifically target HNE. We determined the specificity of the designed inhibitors and their inhibitory efficacy against HNE using biochemical and in vitro methods, including an assay of neutrophil activity. Our aptamers inhibit the elastinolytic activity of HNE with nanomolar potency and are highly specific for HNE and do not target other tested human proteases. As such, this study provides lead compounds suitable for the evaluation of their tissue-protective potential in animal models.

Aptamer functionalized nucleic acid nano drug for targeted synergistic therapy for colon cancer.

Due to its complicated pathophysiology, propensity for metastasis, and poor prognosis, colon cancer is challenging to treat and must be managed with a combination of therapy. Using rolling circle transcription (RCT), this work created a nanosponge therapeutic medication system (AS1411@antimiR-21@Dox). Using the AS1411 aptamer, this approach accomplished targeted delivery to cancer cells. Furthermore, analysis of cell viability, cell apoptosis, cell cycle arrest, reactive oxygen species (ROS) content, and mitochondrial membrane potential (MMP) levels revealed that functional nucleic acid nanosponge drug (FND) can kill cancer cells. Moreover, transcriptomics uncovered a putative mechanism for the FND anti-tumor effect. These pathways, which included mitotic metaphase and anaphase as well as the SMAC-mediated dissociation of the IAP: caspase complexes, were principally linked to the cell cycle and cell death. In conclusion, by triggering cell cycle arrest and apoptosis, the nano-synergistic therapeutic system allowed for the intelligent and effective targeted administration of RNA and chemotherapeutic medicines for colon cancer treatment. The system allowed for payload efficiency while being customizable, targeted, reliable, stable, and affordable.

A Non-G-Quadruplex DNA Aptamer Targeting NCL for Diagnosis and Therapy in Bladder Cancer.

Bladder cancer (BC) is a highly aggressive malignant tumor affecting the urinary system, characterized by metastasis and a poor prognosis that often leads to limited therapeutic success. This study aims to develop a novel DNA aptamer for the diagnosis and treatment of BC using a tissue-based systematic evolution of ligands by an exponential enrichment (SELEX) process. By using SELEX, this work successfully generates a new aptamer named TB-5, which demonstrates a remarkable and specific affinity for nucleolin (NCL) in BC tissues and displays marked biocompatibility both in vitro and in vivo. Additionally, this work shows that NCL is a reliable tissue-specific biomarker in BC. Moreover, according to circular dichroism spectroscopy, TB-5 forms a non-G-quadruplex structure, distinguishing it from the current NCL-targeting aptamer AS1411, and exhibits a distinct binding region on NCL compared to AS1411. Notably, this study further reveals that TB-5 activates NCL function by promoting autophagy and suppressing the migration and invasion of BC cells, which occurs by disrupting mRNA transcription processes. These findings highlight the critical role of NCL in the pathological examination of BC and warrant more comprehensive investigations on anti-NCL aptamers in BC imaging and treatment.

Development of a Novel DNA Aptamer Targeting Colorectal Cancer Cell-Derived Small Extracellular Vesicles as a Potential Diagnostic and Therapeutic Agent.

Colorectal cancer (CRC) as the second leading cause of global cancer deaths poses critical challenges in clinical settings. Cancer-derived small extracellular vesicles (sEVs), which are secreted by cancer cells, have been shown to mediate tumor development, invasion, and even metastasis, and have thus received increasing attention for the development of cancer diagnostic or therapeutic platforms. In the present study, the sEV-targeted systematic evolution of ligands by exponential enrichment (E-SELEX) is developed to generate a high-quality aptamer (CCE-10F) that recognizes and binds to CRC-derived sEVs. Via an in-depth investigation, it is confirmed that this novel aptamer possesses high affinity (Kd = 3.41 nm) for CRC-derived sEVs and exhibits a wide linear range (2.0 × 104 -1.0 × 106 particles µL-1 ) with a limit of detection (LOD) of 1.0 × 103 particles µL-1 . Furthermore, the aptamer discriminates CRC cell-derived sEVs from those derived from normal colon cell, human serum, and other cancer cells, showing high specificity for CRC cell-derived sEVs and significantly suppresses the critical processes of metastasis, including cellular migration, invasion, and angiogenesis, which are originally induced by sEVs themselves. These findings are highly encouraging for the potential use of the aptamer in sEV-based diagnostic and therapeutic applications.

Aptamer-based technology for gastric cancer theranostics.

Gastric cancer is one of the most common causes of cancer death worldwide. This cancer exhibits high molecular and phenotype heterogeneity. The overall survival rate for gastric cancer is very low because it is always diagnosed in the advanced stages. Therefore, early detection and treatment are of great significance. Currently, biomedical studies have tapped the potential clinical applicability of aptamer-based technology for gastric cancer diagnosis and targeted therapy. Herein, we summarize the enrichment and evolution of relevant aptamers, followed by documentation of the recent developments in aptamer-based techniques for early diagnosis and precision therapy for gastric cancers.

Editorial to the IJMS Special Issue "Aptamer-Mediated Cancer Theranostics".

Aptamers have emerged as a new generation of bioaffinity probes with enhanced target binding specificity and selectivity [...].

The Small RNA Landscape in NSCLC: Current Therapeutic Applications and Progresses.

Non-small-cell lung cancer (NSCLC) is the second most diagnosed type of malignancy and the first cause of cancer death worldwide. Despite recent advances, the treatment of choice for NSCLC patients remains to be chemotherapy, often showing very limited effectiveness with the frequent occurrence of drug-resistant phenotype and the lack of selectivity for tumor cells. Therefore, new effective and targeted therapeutics are needed. In this context, short RNA-based therapeutics, including Antisense Oligonucleotides (ASOs), microRNAs (miRNAs), short interfering (siRNA) and aptamers, represent a promising class of molecules. ASOs, miRNAs and siRNAs act by targeting and inhibiting specific mRNAs, thus showing an improved specificity compared to traditional anti-cancer drugs. Nucleic acid aptamers target and inhibit specific cancer-associated proteins, such as "nucleic acid antibodies". Aptamers are also able of receptor-mediated cell internalization, and therefore, they can be used as carriers of secondary agents giving the possibility of producing very highly specific and effective therapeutics. This review provides an overview of the proposed applications of small RNAs for NSCLC treatment, highlighting their advantageous features and recent advancements in the field.

Advantages of Material Biofunctionalization Using Nucleic Acid Aptamers in Tissue Engineering and Regenerative Medicine.

Material engineering is a fundamental issue in the applications of materials in the medical field. One of the aspects of material engineering is incorporating recognition sites on the surface of biomaterials, which plays an essential role in increasing the efficiency of tissue engineering scaffolds in various aspects. The application of peptides and antibodies to establish the recognition and adhesion sites has limitations, such as fragility and instability under physical and chemical processes. Therefore, synthetic ligands such as nucleic acid aptamers have received much attention for easy synthesis, minimal immunogenicity, high specificity, and stability under processing. Due to the effective role of these ligands in increasing the efficiency of engineered constructs in this study, the advantages of nucleic acid aptamers in tissue engineering will be reviewed. Aptamer-functionalized biomaterials can attract endogenous stem cells to wounded areas and organize their actions to facilitate tissue regeneration. This approach harnesses the body's inherent regeneration potential to treat many diseases. Also, increased efficacy in controlled release, slow and targeted drug delivery are important issues in drug delivery for tissue engineering approaches which can be achieved by incorporating aptamers in drug delivery systems. Aptamer-functionalized scaffolds have very applications, such as diagnosis of cancer, hematological infections, narcotics, heavy metals, toxins, controlled release from the scaffolds, and in vivo cell tracing. Aptasensors, as a result of many advantages over other traditional assay methods, can replace older methods. Furthermore, their unique targeting mechanism also targets compounds with no particular receptors. Targeting cell homing, local and targeted drug delivery, cell adhesion efficacy, cytocompatibility and bioactivity of scaffolds, aptamer-based biosensor, and aptamer-functionalized scaffolds are the topics that will be examined in this review study.

Application of aptamer-drug delivery system in the therapy of breast cancer.

Despite significant treatment advances, breast cancer remains the leading cause of cancer death in women. From the current treatment situation, in addition to developing chemoresistant tumours, distant organ metastasis, and recurrences, patients with breast cancer often have a poor prognosis. Aptamers as "chemical antibodies" may be a way to resolve this dilemma. Aptamers are single-stranded, non-coding oligonucleotides (DNA or RNA), resulting their many advantages, including stability for long-term storage, simplicity of synthesis and function, and low immunogenicity, a high degree of specificity and antidote. Aptamers have gained popularity as a method for diagnosing and treating specific tumors in recent years. This article introduces the application of ten different aptamer delivery systems in the treatment and diagnosis of breast cancer, and systematically reviews their latest research progress in breast cancer treatment and diagnosis. It provides a new direction for the clinical treatment of breast cancer.

Novel nanotherapeutics for cancer immunotherapy by CTLA-4 aptamer-functionalized albumin nanoparticle loaded with antihistamine.

INTRODUCTION: Immune checkpoint blockade (ICB) is a promising strategy for cancer treatment and has generated remarkable clinical results against multiple malignancies. Exploration of new technical approaches to further boost the therapeutic efficacy of ICB is of potential medical importance. In this study, we designed a novel nanotherapeutics for ICB immunotherapy. METHODS: CTLA-4 aptamers were conjugated to the surface of albumin nanoparticle to construct an aptamer-modified nanostructure (Apt-NP). To improve ICB efficacy, fexofenadine (FEXO), an antihistamine, was encapsulated into Apt-NP to make a drug-loaded nanoparticle (Apt-NP-FEXO). The antitumor efficacies of Apt-NP and Apt-NP-FEXO were evaluated in vitro and in vivo. RESULTS: Apt-NP and Apt-NP-FEXO had average diameters of 149 nm and 159 nm, respectively. Similar to free CTLA-4 aptamers, Apt-modified NPs could selectively bind with CTLA-4 positive cells and improve lymphocyte-mediated antitumor cytotoxicity in vitro. In animal studies, compared with free CTLA-4 aptamer, Apt-NP significantly enhanced antitumor immunity. Moreover, Apt-NP-FEXO further improved antitumor efficacy vs. Apt-NP in vivo. CONCLUSION: The results suggest that Apt-NP-FEXO represents a novel strategy to improve ICB outcome and may have application potential in cancer immunotherapy.

Unravelling the enigma of siRNA and aptamer mediated therapies against pancreatic cancer.

Pancreatic cancer (PC) is a fatal disease that has a poor 5-year survival rate. The poor prognosis can be attributed to both troublesome detections at the initial stage, which makes the majority of the treatment options largely unsuccessful and leads to extensive metastasis, as well as to its distinct pathophysiological characteristics, such as rich desmoplastic tumours bounded by dysplastic and hypo perfused vessels restricting the mobility of therapeutic agents. Continued attempts have been made to utilise innovative measures for battling PC to increase the therapeutic effectiveness of therapies and overcome their cytotoxicity. Combined cancer targeting and gene silencing approach has shown improved outcomes in patients' survival rates and quality of life, offering a potential solution to therapeutic complications. It particularly targets various barriers to alleviate delivery problems and diminish tumour recurrence and metastasis. While aptamers, a type of single-stranded nucleic acids with strong binding affinity and specificity to target molecules, have recently surfaced as a viable PC strategy, siRNA can interfere with the expression of certain genes. By concurrently suppressing genes and boosting targeted approach, the cocktail of siRNA/Aptamer and other therapeutic drugs can circumvent the multi-drug resistance phenomena. Additionally, combination therapy with additive or synergistic effects can considerably increase the therapeutic efficacy of anti-cancer medications. This study outlines the primary difficulties in treating PC, along with recent developments in siRNA/Aptamer mediated drug delivery to solve the major hiccup of oncology field.