Cargo Delivery Research Articles

Plant-derived Exosomes: Pioneering Breakthroughs in Therapeutics, Targeted Drug Delivery, and Regenerative Medicine.

Small extracellular vesicles called exosomes, which cells release, have drawn a lot of attention recently because of their ability to serve as therapeutic delivery systems for drugs and regenerative medicine applications. The investigation of plant-based exosomes as a cutting-edge platform for drug administration has emerged as an enticing research topic. A summary of the pharmaceutical feasibility of exosomes generated from plants and their uses in drug delivery along with regenerative medicine are the goals of this review study. Plant exosomes can be combined into nanoparticlebased medication delivery systems to increase their stability, targeting, and cargo delivery capabilities. By loading plant exosomes with therapeutic compounds and encapsulating them within nanoparticles, controlled release and targeted distribution to specific cells or tissues may be achieved. In gene therapy, plant exosomes can be modified to carry nucleic acids like plasmid DNA, siRNA, or miRNA. Effective gene delivery and therapeutic gene expression regulation can be accomplished by encasing nucleic acids in exosomes or surface-modifying exosomes to improve their interaction with target cells. In this review, we through the history and features of plant exosomes, examine how they differ from mammalian exosomes, and consider how they may be used for gene therapy, tissue regeneration, and targeted medication delivery. The difficulties and prospects for creating exosomebased plant medicines are also explored.

Enhancing Targeted Drug Delivery through Cell-Specific Endosomal Escape.

Endosome is a major barrier in the intracellular delivery of drugs, especially for biologics, such as proteins, peptides, and nucleic acids. After being endocytosed, these cargos will be trapped inside the endosomal compartments and finally degraded in the lysosomes. Thus, various strategies have been developed to facilitate the escape of cargos from the endosomes to improve the intracellular delivery efficiency. While the majority of the studies are focusing on strengthening the endosomal escape capability to maximize the delivery outcome, recent evidence suggests that a careful control of the endosomal escape process could provide opportunity for targeted drug delivery. In this concept review, we examined current delivery systems that can sense intra-endosomal factors or external stimuli for controlling endosomal escape toward a targeted intracellular delivery of cargos. Furthermore, the prospects and challenges of such strategies are discussed.

СОВРЕМЕННЫЕ ТЕНДЕНЦИИ ЛОГИСТИЧЕСКИХ ПРОЦЕССОВ ПЕРЕВОЗКИ КОНТЕЙНЕРОВ В РОССИИ

The article examines the current trends in the logistics processes of container transportation in Russia and describes the stages of the logistics process of container cargo delivery. Special attention is paid to the dynamics of container transportation with the identification of the causes of changes.

Photoresponsive Hydrogels for Tissue Engineering.

Hydrophilic and biocompatible hydrogels are widely applied as ideal scaffolds in tissue engineering. The "smart" gelation material can alter its structural, physiochemical, and functional features in answer to various endo/exogenous stimuli to better biomimic the endogenous extracellular matrix for the engineering of cells and tissues. Light irradiation owns a high spatial-temporal resolution, complete biorthogonal reactivity, and fine-tunability and can thus induce physiochemical reactions within the matrix of photoresponsive hydrogels with good precision, efficiency, and safety. Both gel structure (e.g., geometry, porosity, and dimension) and performance (like conductivity and thermogenic or mechanical properties) can hence be programmed on-demand to yield the biochemical and biophysical signals regulating the morphology, growth, motility, and phenotype of engineered cells and tissues. Here we summarize the strategies and mechanisms for encoding light-reactivity into a hydrogel and demonstrate how fantastically such responsive gels change their structure and properties with light irradiation as desired and thus improve their applications in tissue engineering including cargo delivery, dynamic three-dimensional cell culture, and tissue repair and regeneration, aiming to provide a basis for more and better translation of photoresponsive hydrogels in the clinic.

3D Computational Modeling of Defective Early Endosome Distribution in Human iPSC-Based Cardiomyopathy Models.

Intracellular cargo delivery via distinct transport routes relies on vesicle carriers. A key trafficking route distributes cargo taken up by clathrin-mediated endocytosis (CME) via early endosomes. The highly dynamic nature of the endosome network presents a challenge for its quantitative analysis, and theoretical modelling approaches can assist in elucidating the organization of the endosome trafficking system. Here, we introduce a new computational modelling approach for assessment of endosome distributions. We employed a model of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) with inherited mutations causing dilated cardiomyopathy (DCM). In this model, vesicle distribution is defective due to impaired CME-dependent signaling, resulting in plasma membrane-localized early endosomes. We recapitulated this in iPSC-CMs carrying two different mutations, TPM1-L185F and TnT-R141W (MUT), using 3D confocal imaging as well as super-resolution STED microscopy. We computed scaled distance distributions of EEA1-positive vesicles based on a spherical approximation of the cell. Employing this approach, 3D spherical modelling identified a bi-modal segregation of early endosome populations in MUT iPSC-CMs, compared to WT controls. Moreover, spherical modelling confirmed reversion of the bi-modal vesicle localization in RhoA II-treated MUT iPSC-CMs. This reflects restored, homogeneous distribution of early endosomes within MUT iPSC-CMs following rescue of CME-dependent signaling via RhoA II-dependent RhoA activation. Overall, our approach enables assessment of early endosome distribution in cell-based disease models. This new method may provide further insight into the dynamics of endosome networks in different physiological scenarios.

Chondrocyte-targeted exosome-mediated delivery of Nrf2 alleviates cartilaginous endplate degeneration by modulating mitochondrial fission

BackgroundCartilaginous endplate (CEP) degeneration, which is an important contributor to intervertebral disc degeneration (IVDD), is characterized by chondrocyte death. Accumulating evidence has revealed that dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and dysfunction lead to apoptosis during CEP degeneration and IVDD. Exosomes are promising agents for the treatment of many diseases, including osteoporosis, osteosarcoma, osteoarthritis and IVDD. Despite their major success in drug delivery, the full potential of exosomes remains untapped.Materials and methodsIn vitro and in vivo models of CEP degeneration were established by using lipopolysaccharide (LPS). We designed genetically engineered exosomes (CAP-Nrf2-Exos) expressing chondrocyte-affinity peptide (CAP) on the surface and carrying the antioxidant transcription factor nuclear factor E2-related factor 2 (Nrf2). The affinity between CAP-Nrf2-Exos and CEP was evaluated by in vitro internalization assays and in vivo imaging assays. qRT‒PCR, Western blotting and immunofluorescence assays were performed to examine the expression level of Nrf2 and the subcellular localization of Nrf2 and Drp1. Mitochondrial function was measured by the JC-1 probe and MitoSOX Red. Mitochondrial morphology was visualized by MitoTracker staining and transmission electron microscopy (TEM). After subendplate injection of the engineered exosomes, the degree of CEP degeneration and IVDD was validated radiologically and histologically.ResultsWe found that the cargo delivery efficiency of exosomes after cargo packaging was increased by surface modification. CAP-Nrf2-Exos facilitated chondrocyte-targeted delivery of Nrf2 and activated the endogenous antioxidant defence system in CEP cells. The engineered exosomes inhibited Drp1 S616 phosphorylation and mitochondrial translocation, thereby preventing mitochondrial fragmentation and dysfunction. LPS-induced CEP cell apoptosis was alleviated by CAP-Nrf2-Exo treatment. In a rat model of CEP degeneration, the engineered exosomes successfully attenuated CEP degeneration and IVDD and exhibited better repair capacity than natural exosomes.ConclusionCollectively, our findings showed that exosome-mediated chondrocyte-targeted delivery of Nrf2 was an effective strategy for treating CEP degeneration.Graphic abstract CAP-Nrf2-Exos delivered Nrf2 into CEP cells and alleviated LPS-induced apoptosis by inhibiting Drp1-mediated mitochondrial fission

Insight into the Functional Dynamics and Challenges of Exosomes in Pharmaceutical Innovation and Precision Medicine.

Of all the numerous nanosized extracellular vesicles released by a cell, the endosomal-originated exosomes are increasingly recognized as potential therapeutics, owing to their inherent stability, low immunogenicity, and targeted delivery capabilities. This review critically evaluates the transformative potential of exosome-based modalities across pharmaceutical and precision medicine landscapes. Because of their precise targeted biomolecular cargo delivery, exosomes are posited as ideal candidates in drug delivery, enhancing regenerative medicine strategies, and advancing diagnostic technologies. Despite the significant market growth projections of exosome therapy, its utilization is encumbered by substantial scientific and regulatory challenges. These include the lack of universally accepted protocols for exosome isolation and the complexities associated with navigating the regulatory environment, particularly the guidelines set forth by the U.S. Food and Drug Administration (FDA). This review presents a comprehensive overview of current research trajectories aimed at addressing these impediments and discusses prospective advancements that could substantiate the clinical translation of exosomal therapies. By providing a comprehensive analysis of both the capabilities and hurdles inherent to exosome therapeutic applications, this article aims to inform and direct future research paradigms, thereby fostering the integration of exosomal systems into mainstream clinical practice.

Ameliorative delivery of docetaxel and curcumin using PEG decorated lipomers: A cutting-edge in-vitro/ in-vivo appraisal

The development of a PEG-decorated lipid-polymer hybrid system camouflaged with natural and synthetic chemotherapeutic moieties is an influential approach melding the biomimetic properties of long-circulating vesicles to utilize different mechanisms to dwindle the tumor growth. Therefore, a safe and efficient lipid-coated nano-particulate system (LCNPs) was proposed to investigate the in-vitro, ex-vivo and in-vivo demeanors of such amalgamation.Docetaxel loaded PLGA nanoparticles (DTX-NPs) were prepared by solvent evaporation while curcumin liposomes were mapped out using the film hydration method. Physicochemical characterizations were executed in terms of size, surface morphology, differential scanning calorimetry (DSC) and fourier-transform infrared spectroscopy (FTIR). In-vitro cytotoxicity was effectuated using MCF-7 cell line. Hemolysis, erythrocyte aggregation and acute in-vivo toxicity were carried out to establish the biocompatibility. The hydrodynamic diameters of samples were in the nano-range and corresponded to the findings of scanning electron microscopy (SEM) and atomic force microscopy (AFM). The absence of distinctive peaks of DTX-NPs in FTIR and DSC analysis of LCNPs depicts the shielding of the lipid bilayer over the nanoparticle. Cytotoxicity induced by the LCNPs represented the efficient delivery of cargo to the tumor cells. LCNPs also exhibited the least toxicity under ex-vivo and in-vivo circumstances compared to free drugs. Additionally, histological studies showed no evidence of substantial necrosis. Additionally, histological studies showed no evidence of notable necrosis.

Extracellular Vesicles in Lung Cancer: Implementation in Diagnosis and Therapeutic Perspectives.

Lung cancer represents the leading cause of cancer-related mortality worldwide, with around 1.8 million deaths in 2020. For this reason, there is an enormous interest in finding early diagnostic tools and novel therapeutic approaches, one of which is extracellular vesicles (EVs). EVs are nanoscale membranous particles that can carry proteins, lipids, and nucleic acids (DNA and RNA), mediating various biological processes, especially in cell-cell communication. As such, they represent an interesting biomarker for diagnostic analysis that can be performed easily by liquid biopsy. Moreover, their growing dataset shows promising results as drug delivery cargo. The aim of our work is to summarize the recent advances in and possible implications of EVs for early diagnosis and innovative therapies for lung cancer.

Magnetic Microrobots for In Vivo Cargo Delivery: A Review.

Magnetic microrobots, with their small size and agile maneuverability, are well-suited for navigating the intricate and confined spaces within the human body. In vivo cargo delivery within the context of microrobotics involves the use of microrobots to transport and administer drugs and cells directly to the targeted regions within a living organism. The principal aim is to enhance the precision, efficiency, and safety of therapeutic interventions. Despite their potential, there is a shortage of comprehensive reviews on the use of magnetic microrobots for in vivo cargo delivery from both research and engineering perspectives, particularly those published after 2019. This review addresses this gap by disentangling recent advancements in magnetic microrobots for in vivo cargo delivery. It summarizes their actuation platforms, structural designs, cargo loading and release methods, tracking methods, navigation algorithms, and degradation and retrieval methods. Finally, it highlights potential research directions. This review aims to provide a comprehensive summary of the current landscape of magnetic microrobot technologies for in vivo cargo delivery. It highlights their present implementation methods, capabilities, and prospective research directions. The review also examines significant innovations and inherent challenges in biomedical applications.

КРИТЕРІАЛЬНИЙ ВПЛИВ НА ВИБІР ВИДУ ТРАНСПОРТНОГО СПОЛУЧЕННЯ ПРИ ОРГАНІЗАЦІЇ ДОСТАВКИ ВАНТАЖІВ В УМОВАХ МІЖНАРОДНОЇ ІНТЕГРАЦІЇ

Introduction. The organisation of cargo delivery in various transport connection options requires the identification of the most optimal parameters of transportation by certain transport modes and the development of better transport connections. The systematisation of transport and logistics processes requires a comprehensive solution to the problems of organising the delivery of goods in international multimodal connections. The growing demands of the freight clientele are becoming a key factor in the competition between both carriers and logistics operators to serve more profitable cargo flows. Problem Statement. International integration processes involve interaction between all participants in international cargo delivery, and its reliability depends on the effectiveness of its organisation. Ensuring high-quality transport services for a particular cargo delivery is only possible if the criteria are correctly selected and adequately assessed. Purpose. To determine the criteria of influence on the choice of transport mode in the organisation of cargo delivery, taking into account the factor influence characterising the carrying capacity of each transport mode serving a particular order, as well as the synergy of their interaction.

Synthesis and Assembly of Photoresponsive Colloidal Tubes.

Inspired by the sophisticated multicomponent and multistage assembly of proteins and their mixtures in living cells, this study rationally designs and fabricates photoresponsive colloidal tubes that can self-assemble and hybrid-assemble when mixed with colloidal spheres and rods. Time-resolved observation and computer simulation reveal that the assembly is driven by phoretic attraction originating from osmotic pressures. These pressures are induced by the chemical concentration gradients generated by the photochemical reaction caused by colloidal tubes in a H2O2 solution under ultraviolet (UV) irradiation. The assembled structure is dictated by the size and shape of the constituent colloids as well as the intensity of the UV irradiation. Additionally, the resulting assembly can undergo self-propelled motion originating from the broken symmetry of the surrounding concentration gradients. This motion can be steered by a magnetic field and used for microscale cargo delivery. The study demonstrates a facile synthesis method for colloidal tubes and highlights their unique potential for controlled, hierarchical self-assembly and hybrid-assembly.

Covalent Attachment of Horseradish Peroxidase to Single‐Walled Carbon Nanotubes for Hydrogen Peroxide Detection

AbstractSingle‐walled carbon nanotubes (SWCNTs) are desirable nanoparticles for sensing biological analytes due to their photostability and intrinsic near‐infrared fluorescence. Previous strategies for generating SWCNT nanosensors have leveraged nonspecific adsorption of sensing modalities to the hydrophobic SWCNT surface that often require engineering new molecular recognition elements. An attractive alternate strategy is to leverage pre‐existing molecular recognition of proteins for analyte specificity, yet attaching proteins to SWCNT for nanosensor generation remains challenging. Toward this end, a generalizable platform is introduced to generate protein‐SWCNT‐based optical sensors and use this strategy to synthesize a hydrogen peroxide (H2O2) nanosensor by covalently attaching horseradish peroxidase (HRP) to the SWCNT surface. A concentration‐dependent response is demonstrated to H2O2, confirming the nanosensor can image H2O2 in real‐time, and assess the nanosensor's selectivity for H2O2 against a panel of biologically relevant analytes. Taken together, these results demonstrate successful covalent attachment of enzymes to SWCNTs while preserving both intrinsic SWCNT fluorescence and enzyme function. It is anticipated this platform can be adapted to covalently attach other proteins of interest including other enzymes for sensing or antibodies for targeted imaging and cargo delivery.

Magoctopus: Bio-inspired small-scale magnetic soft octopus with programmable shape morphing and motions

Microscale magnetic soft robots, with their tetherless propulsion capability, non-invasive interaction with the environment, and high adaptability to confined and unstructured spaces, hold tremendous promise in the field of biomedicine. These robots can navigate flexibly within narrow internal environments, such as blood vessels and organs, under remote magnetic field manipulation. However, the lack grasping capabilities in most existing microscale magnetic soft robots, has restricted their utility in medical applications. Inspired by the movement and predatory behavior of octopuses in the ocean, we have developed a microscale biomimetic magnetic octopus (Magoctopus), capable of mimicking biological functions such as movement and object grasping in liquid environments. The Magoctopus, with a total length of 17.30 mm and weight of 0.24 g, features a polystyrene head and six tentacles made of VHB (Very hard bond) material embedded with SmFeN powder for magnetic programming. By utilizing horizontally alternating magnetic fields, the six tentacles of Magoctopus can exhibit pre-programmed bending deformations to mimic the motion patterns of octopus tentacles. Furthermore, the Magoctopus has demonstrated capabilities in cargo delivery, targeted drug delivery, and other potential application, making it suitable for transportation within complex environments, biomedical applications, and beyond.

Russian Logistics and Supply Chain Management: Challenges and Relevant Solutions

Relevance of the research. The article considers a forced paradigm shift and systemic restructuring of Russian logistics due to the introduction of sanctions barriers and partial trade blockade, which, in addition to restricting Russian exports and imports, threatens digital technological transformations in supply chain management and occurs against the backdrop of tightening international environmental requirements for business activities, including logistics.The purpose of the research is to review changes taking place in Russian logistics and to analyze corresponding solutions for supply chain management.Design, methods, information base. The methodological framework of the research consists of fundamentals of logistics and supply chain management, elements of economic systems digital development concept and basic principles of ecological economics. The main research methods are collecting information from secondary sources, practicing experts in-depth interviewing, specialists surveying, computer content and PESTEL analysis. The methodological basis is formed by the basics of logistics and supply chain management, elements of the concept of digital development of economic systems and basic principles of ecological economy. The information base of the research consisted of interview transcripts, survey results, bibliographic documents, and Internet text files.Findings. As a result of the work, external challenges and influencing factors are identified, internal processes, drivers and trends characteristic of Russian logistics and supply chain management today are identified and described. Relevant decisions made by Russian logisticians in the current period are systematized and evaluated. The flexibility and sustainability of supply chains was confirmed, as well as the high adaptability of Russian logistics to radical transformation of business environment and operating conditions.Originality/value of the research. The study showed that despite the deglobalization of Russian logistics, it remains possible to manage any cargo delivery to Russia from anywhere in the world. The material may be useful both to Russian logistics practitioners and to persons studying or teaching the discipline “Logistics”.

Investigating Internalization of Reporter-Protein-Functionalized Polyhedrin Particles by Brain Immune Cells.

Achieving sustained drug delivery to the central nervous system (CNS) is a major challenge for neurological injury and disease, and various delivery vehicles are being developed to achieve this. Self-assembling polyhedrin crystals (POlyhedrin Delivery System; PODS) are being exploited for the delivery of therapeutic protein cargo, with demonstrated efficacy in vivo. However, to establish the utility of PODS for neural applications, their handling by neural immune cells (microglia) must be documented, as these cells process and degrade many biomaterials, often preventing therapeutic efficacy. Here, primary mouse cortical microglia were cultured with a GFP-functionalized PODS for 24 h. Cell counts, cell morphology and Iba1 expression were all unaltered in treated cultures, indicating a lack of acute toxicity or microglial activation. Microglia exhibited internalisation of the PODS, with both cytosolic and perinuclear localisation. No evidence of adverse effects on cellular morphology was observed. Overall, 20-40% of microglia exhibited uptake of the PODS, but extracellular/non-internalised PODS were routinely present after 24 h, suggesting that extracellular drug delivery may persist for at least 24 h.

Bioreversible Anionic Cloaking Enables Intracellular Protein Delivery with Ionizable Lipid Nanoparticles.

Protein-based therapeutics comprise a rapidly growing subset of pharmaceuticals, but enabling their delivery into cells for intracellular applications has been a longstanding challenge. To overcome the delivery barrier, we explored a reversible, bioconjugation-based approach to modify the surface charge of protein cargos with an anionic "cloak" to facilitate electrostatic complexation and delivery with lipid nanoparticle (LNP) formulations. We demonstrate that the conjugation of lysine-reactive sulfonated compounds can allow for the delivery of various protein cargos using FDA-approved LNP formulations of the ionizable cationic lipid DLin-MC3-DMA (MC3). We apply this strategy to functionally deliver RNase A for cancer cell killing as well as a full-length antibody to inhibit oncogenic β-catenin signaling. Further, we show that LNPs encapsulating cloaked fluorescent proteins distribute to major organs in mice following systemic administration. Overall, our results point toward a generalizable platform that can be employed for intracellular delivery of a wide range of protein cargos.

Conditional Cell Penetration of Masked CPPs by an ADEPT-like Approach.

The intracellular delivery of cargos via cell penetrating peptides (CPPs) holds significant promise as a drug delivery vehicle, but a major issue is their lack of cell type specificity, which can lead to detrimental off-target effects. We use an ADEPT-like concept to introduce conditional and selective activation of cellular uptake by using the lysine-rich, cationic, and amphiphilic L17E peptide as a model CPP. By masking the lysine residues of the L17E peptide with enzyme-cleavable acetyl protecting groups, the delivery of the covalently conjugated fluorophore TAMRA to HeLa cells was diminished. Recovery of cellular uptake could be achieved by deacetylation of the masked acetylated L17E peptide using the NAD-dependent sirtuin 2 (SirT2) deacetylase in vitro. Finally, trastuzumab-SirT2 and anti-B7H3-SirT2 antibody-enzyme conjugates were generated for the conditional and selective delivery of a cryptophycin cytotoxin by the L17E peptide. While the masked peptide still demonstrated some cytotoxicity, selective cell killing mediated by the antibody-enzyme conjugates was observed.

Exploring the Localization of Siderophore-Mediated Cargo Delivery in Gram-Negative Bacteria Using 3-Hydroxypyridin-4(1H)-one-Fluorescein Probes.

The design of siderophore-antibiotic conjugates is a promising strategy to overcome drug resistance in negative bacteria. However, accumulating studies have shown that only those antibiotics acting on the cell wall or cell membrane multiply their antibacterial effects when coupled with siderophores, while antibiotics acting on targets in the cytoplasm of bacteria do not show an obvious enhancement of their antibacterial effects when coupled with siderophores. To explore the causes of this phenomenon, we synthesized several conjugate probes using 3-hydroxypyridin-4(1H)-ones as siderophores and replacing the antibiotic cargo with 5-carboxyfluorescein (5-FAM) or malachite green (MG) cargo. By monitoring changes in the fluorescence intensity of FAM conjugate 20 in bacteria, the translocation of the conjugate across the outer membranes of Gram-negative pathogens was confirmed. Further, the use of the fluorogen activating protein(FAP)/MG system revealed that 3-hydroxypyridin-4(1H)-one-MG conjugate 26 was ultimately distributed mainly in the periplasm rather than being translocated into the cytosol of Escherichia coli and Pseudomonas aeruginosa PAO1. Additional mechanistic studies suggested that the uptake of the conjugate involved the siderophore-dependent iron transport pathway and the 3-hydroxypyridin-4(1H)-ones siderophore receptor-dependent mechanism. Meanwhile, we demonstrated that the conjugation of 3-hydroxypyridin-4(1H)-ones to the fluorescein 5-FAM can reduce the possibility of the conjugates crossing the membrane layers of mammalian Vero cells by passive diffusion, and the advantages of the mono-3-hydroxypyridin-4(1H)-ones as a delivery vehicle in the design of conjugates compared to the tri-3-hydroxypyridin-4(1H)-ones. Overall, this work reveals the localization rules of 3-hydroxypyridin-4(1H)-ones as siderophores to deliver the cargo into Gram-negative bacteria. It provides a theoretical basis for the subsequent design of siderophore-antibiotic conjugates, especially based on 3-hydroxypyridin-4(1H)-ones as siderophores.

Advancements in Aptamer-Driven DNA Nanostructures for Precision Drug Delivery.

DNA nanostructures exhibit versatile geometries and possess sophisticated capabilities not found in other nanomaterials. They serve as customizable nanoplatforms for orchestrating the spatial arrangement of molecular components, such as biomolecules, antibodies, or synthetic nanomaterials. This is achieved by incorporating oligonucleotides into the design of the nanostructure. In the realm of drug delivery to cancer cells, there is a growing interest in active targeting assays to enhance efficacy and selectivity. The active targeting approach involves a "key-lock" mechanism where the carrier, through its ligand, recognizes specific receptors on tumor cells, facilitating the release of drugs. Various DNA nanostructures, including DNA origami, Tetrahedral, nanoflower, cruciform, nanostar, nanocentipede, and nanococklebur, can traverse the lipid layer of the cell membrane, allowing cargo delivery to the nucleus. Aptamers, easily formed in vitro, are recognized for their targeted delivery capabilities due to their high selectivity for specific targets and low immunogenicity. This review provides a comprehensive overview of recent advancements in the formation and modification of aptamer-modified DNA nanostructures within drug delivery systems.