Nucleic acid aptamers are single-stranded DNA or RNA of 20–100 nucleotides in length that have attracted substantial scientific interest due to their ability to specifically bind to target molecules via the formation of three-dimensional structures. Compared to traditional protein antibodies, aptamers have several advantages, such as their small size, high binding affinity, specificity, flexible structure, being chemical synthesizable and modifiable, good biocompatibility, high stability and low immunogenicity, which all contribute to their widely applications in the biomedical field. To date, much progress has been made in the study and applications of aptamers, however, detailed information on how aptamers bind to their targets is still scarce. Over the past few decades, many methods have been introduced to investigate the aptamer–target binding process, such as measuring the main kinetic or thermodynamic parameters, detecting the structural changes of the binding complexes, etc. Apart from traditional physicochemical methods, various types of molecular docking programs have been applied to simulate the aptamer–target interactions, while these simulations also have limitations. To facilitate the further research on the interactions, herein, we provide a brief review to illustrate the recent advances in the study of aptamer–target interactions. We summarize the binding targets of aptamers, such as small molecules, macromolecules, and even cells. Their binding constants (K_D) are also summarized. Methods to probe the aptamer–target binding process, such as surface plasmon resonance (SPR), circular dichroism spectroscopy (CD), isothermal titration calorimetry (ITC), footprinting assay, truncation and mutation assay, nuclear magnetic resonance spectroscopy (NMR), X-ray crystallography and molecular docking simulation are indicated. The binding forces mediating the aptamer–target interactions, such as hydrogen bonding, electrostatic interaction, the hydrophobic effect, π–π stacking and van der Waals forces are summarized. The challenges and future perspectives are also discussed.

: Aptamers are single-stranded DNA or RNA with 20-100 nucleotides in length that can specifically bind to target molecules via formed three-dimensional structures. These innovative targeting molecules have attracted an increasing interest in the biomedical field. Compared to traditional protein antibodies, aptamers have several advantages, such as small size, high binding affinity, specificity, good biocompatibility, high stability and low immunogenicity, which all contribute to their wide application in the biomedical field. Aptamers can bind to the receptors on the cell membrane and mediate themselves or conjugated nanoparticles to enter into cells. Therefore, aptamers can be served as ideal targeting ligands for drug delivery. Since their excellent properties, different aptamer-mediated drug delivery systems had been developed for cancer therapy. This review provides a brief overview of recent advances in drug delivery systems based on aptamers. The advantages, challenges and future prospectives are also discussed.

Conventional tumor-targeted drug delivery systems (DDSs) face challenges, such as unsatisfied systemic circulation, low targeting efficiency, poor tumoral penetration, and uncontrolled drug release. Recently, tumor cellular molecules-triggered DDSs have aroused great interests in addressing such dilemmas. With the introduction of several additional functionalities, the properties of these smart DDSs including size, surface charge and ligand exposure can response to different tumor microenvironments for a more efficient tumor targeting, and eventually achieve desired drug release for an optimized therapeutic efficiency. This review highlights the recent research progresses on smart tumor environment responsive drug delivery systems for targeted drug delivery. Dynamic targeting strategies and functional moieties sensitive to a variety of tumor cellular stimuli, including pH, glutathione, adenosine-triphosphate, reactive oxygen species, enzyme and inflammatory factors are summarized. Special emphasis of this review is placed on their responsive mechanisms, drug loading models, drawbacks and merits. Several typical multi-stimuli responsive DDSs are listed. And the main challenges and potential future development are discussed.

The emergence of the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome-editing system has brought about a significant revolution in the realm of managing human diseases, establishing animal models, and so on. To fully harness the potential of this potent gene-editing tool, ensuring efficient and secure delivery to the target site is paramount. Consequently, developing effective delivery methods for the CRISPR/Cas9 system has become a critical area of research. In this review, we present a comprehensive outline of delivery strategies and discuss their biomedical applications in the CRISPR/Cas9 system. We also provide an in-depth analysis of physical, viral vector, and non-viral vector delivery strategies, including plasmid-, mRNA- and protein-based approach. In addition, we illustrate the biomedical applications of the CRISPR/Cas9 system. This review highlights the key factors affecting the delivery process and the current challenges facing the CRISPR/Cas9 system, while also delineating future directions and prospects that could inspire innovative delivery strategies. This review aims to provide new insights and ideas for advancing CRISPR/Cas9-based delivery strategies and to facilitate breakthroughs in biomedical research and therapeutic applications.