Trop2-targeted therapies in solid tumors: advances and future directions.

Trophoblast cell surface antigen 2 (Trop2) is overexpressed in a range of solid tumors and participants in multiple oncogenic signaling pathways, making it an attractive therapeutic target. In the past decade, the rapid development of various Trop2-targeted therapies, notably marked by the advent of the antibody-drug conjugate (ADC), revolutionized the outcome for patients facing Trop2-positive tumors with limited treatment opinions, such as triple-negative breast cancer (TNBC). This review provides a comprehensive summary of advances in Trop2-targeted therapies, including ADCs, antibodies, multispecific agents, immunotherapy, cancer vaccines, and small molecular inhibitors, along with in-depth discussions on their designs, mechanisms of action (MOAs), and limitations. Additionally, we emphasize the clinical research progress of these emerging Trop2-targeted agents, focusing on their clinical application and therapeutic efficacy against tumors. Furthermore, we propose directions for future research, such as enhancing our understanding of Trop2's structure and biology, exploring the best combination strategies, and tailoring precision treatment based on Trop2 testing methodologies.

Graphene oxide-functionalized molecular beacon for real-time interference-free detection of Ki-67 mRNA in living cells.

Molecular beacons (MBs) based on hairpin-shaped oligonucleotides are captivating owing to their capability to enable effective real-time detection of cytosolic mRNA in living cells. However, DNase in the nucleus and lysosome could induce the degradation of oligonucleotides in MBs, leading to the generation of false-positive signals. Herein, a graphene oxide (GO) nanosheet was applied as a nanocarrier for MBs to greatly enhance the anti-interference of the easily designed nanoprobe. Advantageously, the absorption capacity of GO for MBs increased with the decrease in pH values, providing the MB-GO nanoprobe with the ability to detect the expression of cytosolic Ki-67 mRNA without interference from DNase Ⅱ in lysosomes. Moreover, the size of GO nanosheets was considerably higher than that of the nuclear pore complex (NPC), which prevented nanoprobes from transition through the NPCs, thereby avoiding the generation of false-positive signals in the nucleus. Altogether, the present work affords a convenient approach for the successful detection of Ki-67 mRNA expression in the cytosol without interference from DNase Ⅰ/Ⅱ in the nucleus/lysosome, which may be potentially further applied for the detection of other cytosolic RNAs.

Ultrathin Flexible Silica Nanosheets with Surface Chemistry-Modulated Affinity to Mammalian Cells.

Flexibility of nanomaterials is challenging but worthy to tune for biomedical applications. Biocompatible silica nanomaterials are under extensive exploration but are rarely observed to exhibit flexibility despite the polymeric nature. Herein, a facile one-step route is reported to ultrathin flexible silica nanosheets (NSs), whose low thickness and high diameter-to-thickness ratio enables folding. Thickness and diameter can be readily tuned to enable controlled flexibility. Mechanism study reveals that beyond the commonly used surfactant, the "uncommon" one bearing two hydrophobic tails play a guiding role in producing sheeted/layered/shelled structures, while addition of ethanol appropriately relieved the strong interfacial tension of the assembled surfactants, which will otherwise produce large curled sheeted structures. With these ultrathin NSs, it is further shown that the cellular preference for particle shape and rigidity is highly dependent on surface chemistry of nanoparticles: under high particle-cell affinity, NSs, and especially the flexible ones will be preferred by mammalian cells for internalization or attachment, while this preference is basically invalid when the affinity is low. Therefore, properties of the ultrathin silica NSs can be effectively expanded and empowered by surface chemistry to realize improved bio-sensing or drug delivery.

Breaking the barrier: Nanoparticle-enhanced radiotherapy as the new vanguard in brain tumor treatment.

The pursuit of effective treatments for brain tumors has increasingly focused on the promising area of nanoparticle-enhanced radiotherapy (NERT). This review elucidates the context and significance of NERT, with a particular emphasis on its application in brain tumor therapy-a field where traditional treatments often encounter obstacles due to the blood-brain barrier (BBB) and tumor cells' inherent resistance. The aims of this review include synthesizing recent advancements, analyzing action mechanisms, and assessing the clinical potential and challenges associated with nanoparticle (NP) use in radiotherapy enhancement. Preliminary preclinical studies have established a foundation for NERT, demonstrating that nanoparticles (NPs) can serve as radiosensitizers, thereby intensifying radiotherapy's efficacy. Investigations into various NP types, such as metallic, magnetic, and polymeric, have each unveiled distinct interactions with ionizing radiation, leading to an augmented destruction of tumor cells. These interactions, encompassing physical dose enhancement and biological and chemical radio sensitization, are crucial to the NERT strategy. Although clinical studies are in their early phases, initial trials have shown promising results in terms of tumor response rates and survival, albeit with mindful consideration of toxicity profiles. This review examines pivotal studies affirming NERT's efficacy and safety. NPs have the potential to revolutionize radiotherapy by overcoming challenges in targeted delivery, reducing off-target effects, and harmonizing with other modalities. Future directions include refining NP formulations, personalizing therapies, and navigating regulatory pathways. NERT holds promise to transform brain tumor treatment and provide hope for patients.

Rational design of multifunctional hydrogels targeting the microenvironment of diabetic periodontitis.

Periodontitis is a chronic inflammatory disease and is the primary contributor to adult tooth loss. Diabetes exacerbates periodontitis, accelerates periodontal bone resorption. Thus, effectively managing periodontitis in individuals with diabetes is a long-standing challenge. This review introduces the etiology and pathogenesis of periodontitis, and analyzes the bidirectional relationship between diabetes and periodontitis. In this review, we comprehensively summarize the four pathological microenvironments influenced by diabetic periodontitis: high glucose microenvironment, bacterial infection microenvironment, inflammatory microenvironment, and bone loss microenvironment. The hydrogel design strategies and latest research development tailored to the four microenvironments of diabetic periodontitis are mainly focused on. Finally, the challenges and potential solutions in the treatment of diabetic periodontitis are discussed. We believe this review will be helpful for researchers seeking novel avenues in the treatment of diabetic periodontitis.

Lead-rivet strategy of growing perovskite nanocrystals for excellent toxicity inhibition and spinning application.

Lead halide perovskite has demonstrated remarkable potential in the wearable field due to its exceptional photoelectric conversion capability. However, its lead toxicity issue has consistently been subject to criticism, significantly impeding its practical application. To address this challenge, an innovative approach called lead-rivet was proposed for the in-situ growth of perovskite crystalline structures. Through the formation of S-Pb bonds, each Pb2+ ion was firmly immobilized on the surface of the silica matrix, enabling in situ growth of perovskite nanocrystals via ion coordination between Cs+ and halide species. The robust S-Pb bonding effectively restricted the mobility of lead ions and stabilized the perovskite structure without relying on surface ligands, thereby not only preventing toxicity leakage but also providing a favorable interface for depositing protective shells. The obtained perovskites exhibit intense and narrow-band fluorescence with full-width at half-maximum less than 23 nm and show excellent stability to high temperature (above 202 °C) and high humidity (water immersion over 27 days), thus making it possible to be used in varies textile technologies including melt spinning and wet spinning. The lead leakage rate of particles is only 4.15 % demonstrating excellent toxicity inhibition performance. The prepared fibers maintained good extensibility and flexibility which could be used for 3D-printing and textiles weaving. Most importantly, the detected Pb2+ leaching was negligible as low as to 0.732 ppb which meet the standard of World Health Organization (WHO) for drinking water (<10 ppb), and the cell survival rate remained 99.196 % for PLA fluorescent filament after 24 h cultivation which showing excellent safety to human body and environment. This study establishes a controllable and highly adaptable synthesis method, thereby providing a promising avenue for the safe utilization of perovskite materials.

Advancing bone regeneration: Unveiling the potential of 3D cell models in the evaluation of bone regenerative materials.

Bone, a rigid yet regenerative tissue, has garnered extensive attention for its impressive healing abilities. Despite advancements in understanding bone repair and creating treatments for bone injuries, handling nonunions and large defects remains a major challenge in orthopedics. The rise of bone regenerative materials is transforming the approach to bone repair, offering innovative solutions for nonunions and significant defects, and thus reshaping orthopedic care. Evaluating these materials effectively is key to advancing bone tissue regeneration, especially in difficult healing scenarios, making it a critical research area. Traditional evaluation methods, including two-dimensional cell models and animal models, have limitations in predicting accurately. This has led to exploring alternative methods, like 3D cell models, which provide fresh perspectives for assessing bone materials' regenerative potential. This paper discusses various techniques for constructing 3D cell models, their pros and cons, and crucial factors to consider when using these models to evaluate bone regenerative materials. We also highlight the significance of 3D cell models in the in vitro assessments of these materials, discuss their current drawbacks and limitations, and suggest future research directions. STATEMENT OF SIGNIFICANCE: This work addresses the challenge of evaluating bone regenerative materials (BRMs) crucial for bone tissue engineering. It explores the emerging role of 3D cell models as superior alternatives to traditional methods for assessing these materials. By dissecting the construction, key factors of evaluating, advantages, limitations, and practical considerations of 3D cell models, the paper elucidates their significance in overcoming current evaluation method shortcomings. It highlights how these models offer a more physiologically relevant and ethically preferable platform for the precise assessment of BRMs. This contribution is particularly significant for "Acta Biomaterialia" readership, as it not only synthesizes current knowledge but also propels the discourse forward in the search for advanced solutions in bone tissue engineering and regeneration.

Evolving Tumor Characteristics and Smart Nanodrugs for Tumor Immunotherapy.

Typical physiological characteristics of tumors, such as weak acidity, low oxygen content, and upregulation of certain enzymes in the tumor microenvironment (TME), provide survival advantages when exposed to targeted attacks by drugs and responsive nanomedicines. Consequently, cancer treatment has significantly progressed in recent years. However, the evolution and adaptation of tumor characteristics still pose many challenges for current treatment methods. Therefore, efficient and precise cancer treatments require an understanding of the heterogeneity degree of various factors in cancer cells during tumor evolution to exploit the typical TME characteristics and manage the mutation process. The highly heterogeneous tumor and infiltrating stromal cells, immune cells, and extracellular components collectively form a unique TME, which plays a crucial role in tumor malignancy, including proliferation, invasion, metastasis, and immune escape. Therefore, the development of new treatment methods that can adapt to the evolutionary characteristics of tumors has become an intense focus in current cancer treatment research. This paper explores the latest understanding of cancer evolution, focusing on how tumors use new antigens to shape their "new faces"; how immune system cells, such as cytotoxic T cells, regulatory T cells, macrophages, and natural killer cells, help tumors become "invisible", that is, immune escape; whether the diverse cancer-associated fibroblasts provide support and coordination for tumors; and whether it is possible to attack tumors in reverse. This paper discusses the limitations of targeted therapy driven by tumor evolution factors and explores future strategies and the potential of intelligent nanomedicines, including the systematic coordination of tumor evolution factors and adaptive methods, to meet this therapeutic challenge.

Versatile filter membrane for effective sampling and real-time quantitative detection of airborne pathogens.

Construction of air filter membranes bearing prominent collecting and transferring capability is highly desirable for detecting airborne pathogens but remains challenging. Here, a hyaluronic acid air filter membrane (HAFM) with tunable heterogeneous micro-nano porous structures is straightforwardly constructed through the ethanol-induced phase separation strategy. Airborne pathogens can be trapped and collected by HAFM with high performance due to the ideal trade-off between removal efficiency and pressure drop. By exempting the sample elution and extraction processes, the HAFM after filtration sampling can not only directly disperse on the agar plate for colony culture but also turn to an aqueous solution for centrifugal enrichment, which significantly reduces the damage and losses of the captured microorganisms. The following combination with ATP bioluminescence endows the HAFM with a real-time quantitative detection function for the captured airborne pathogens. Benefiting from high-efficiency sampling and non-traumatic transfer of airborne pathogens, the real-world bioaerosol concentration can be facilely evaluated by the HAFM-based ATP assay. This work thus not only provides a feasible strategy to fabricate air filter membranes for efficient microbial collection and enrichment but also sheds light on designing advanced protocols for real-time detection of bioaerosols in the field.

Targeting lymph nodes for enhanced cancer vaccination: From nanotechnology to tissue engineering.

Lymph nodes (LNs) occupy a critical position in initiating and augmenting immune responses, both spatially and functionally. In cancer immunotherapy, tumor-specific vaccines are blooming as a powerful tool to suppress the growth of existing tumors, as well as provide preventative efficacy against tumorigenesis. Delivering these vaccines more efficiently to LNs, where antigen-presenting cells (APCs) and T cells abundantly reside, is under extensive exploration. Formulating vaccines into nanomedicines, optimizing their physiochemical properties, and surface modification to specifically bind molecules expressed on LNs or APCs, are common routes and have brought encouraging outcomes. Alternatively, porous scaffolds can be engineered to attract APCs and provide an environment for them to mature, proliferate and migrate to LNs. A relatively new research direction is inducing the formation of LN-like organoids, which have shown positive relevance to tumor prognosis. Cutting-edge advances in these directions and discussions from a future perspective are given here, from which the up-to-date pattern of cancer vaccination will be drawn to hopefully provide basic guidance to future studies.

New-generation advanced PROTACs as potential therapeutic agents in cancer therapy.

Proteolysis-targeting chimeras (PROTACs) technology has garnered significant attention over the last 10 years, representing a burgeoning therapeutic approach with the potential to address pathogenic proteins that have historically posed challenges for traditional small-molecule inhibitors. PROTACs exploit the endogenous E3 ubiquitin ligases to facilitate degradation of the proteins of interest (POIs) through the ubiquitin-proteasome system (UPS) in a cyclic catalytic manner. Despite recent endeavors to advance the utilization of PROTACs in clinical settings, the majority of PROTACs fail to progress beyond the preclinical phase of drug development. There are multiple factors impeding the market entry of PROTACs, with the insufficiently precise degradation of favorable POIs standing out as one of the most formidable obstacles. Recently, there has been exploration of new-generation advanced PROTACs, including small-molecule PROTAC prodrugs, biomacromolecule-PROTAC conjugates, and nano-PROTACs, to improve the in vivo efficacy of PROTACs. These improved PROTACs possess the capability to mitigate undesirable physicochemical characteristics inherent in traditional PROTACs, thereby enhancing their targetability and reducing off-target side effects. The new-generation of advanced PROTACs will mark a pivotal turning point in the realm of targeted protein degradation. In this comprehensive review, we have meticulously summarized the state-of-the-art advancements achieved by these cutting-edge PROTACs, elucidated their underlying design principles, deliberated upon the prevailing challenges encountered, and provided an insightful outlook on future prospects within this burgeoning field.

Gel-confined fabrication of fully bio-based filtration membrane for green capture and rapid detection of airborne microbes.

Air filtration has become a desirable route for collecting airborne microbes. However, the potential biotoxicity and sterilization of current air filtration membranes often lead to undesired inactivation of captured microbes, which greatly limits microbial non-traumatic transfer and recovery. Herein, we report a gel-confined phase separation strategy to rationally fabricate a fully bio-based filtration membrane (SGFM) using soluble soybean polysaccharide and gelatin. The versatile SGFM features fascinating honeycomb micro-nano architecture and hierarchical interconnected porous structures for microbial capture, and achieves a lower pressure drop, higher interception efficiency (99.3%), and superior microbial survivability than commercial gelatin filtration membranes. Particularly, the water-dissolvable SGFM can greatly simplify the elution and extraction process after bioaerosol sampling, thereby bringing about maximum sample transfer and vigorous recovery of collected microbes. Meanwhile, green capture coupled with ATP bioluminescence endows the SGFM with rapid and quantitative detection capability for airborne microbes. This work may pave the way for designing green protocols for the detection of bioaerosols.

Air sampling and ATP bioluminescence for quantitative detection of airborne microbes.

Exposure to bioaerosol contamination has detrimental effects on human health. Recent advances in ATP bioluminescence provide more opportunities for the quantitative detection of bioaerosols. Since almost all active organisms can produce ATP, the amount of airborne microbes can be easily measured by detecting ATP-driven bioluminescence. The accurate evaluation of microorganisms mainly relies on following the four key steps: sampling and enrichment of airborne microbes, lysis for ATP extraction, enzymatic reaction, and measurement of luminescence intensity. To enhance the effectiveness of ATP bioluminescence, each step requires innovative strategies and continuous improvement. In this review, we summarized the recent advances in the quantitative detection of airborne microbes based on ATP bioluminescence, which focuses on the advanced strategies for improving sampling devices combined with ATP bioluminescence. Meanwhile, the optimized and innovative strategies for the remaining three key steps of the ATP bioluminescence assay are highlighted. The aim is to reawaken the prosperity of ATP bioluminescence and promote its wider utilization for efficient, real-time, and accurate detection of airborne microbes.

5-Hydroxytryptophan acts as a gap junction inhibitor to limit the spread of chemotherapy-induced cardiomyocyte injury and mitochondrial dysfunction.

Anthracycline chemotherapeutics like doxorubicin (DOX) are widely used against various cancers but are accompanied by severe cardiotoxic effects that can lead to heart failure. Through whole transcriptome sequencing and pathological tissue analysis in a murine model, our study has revealed that DOX impairs collagen expression in the early phase, causing extracellular matrix anomalies that weaken the mechanical integrity of the heart. This results in ventricular wall thinning and dilation, exacerbating cardiac dysfunction. In this work, we have identified 5-hydroxytryptophan (5-HTP) as a potent inhibitor of gap junction communication. This inhibition is key to limiting the spread of DOX-induced cardiotoxicity. Treatment with 5-HTP effectively countered the adverse effects of DOX on the heart, preserving ventricular structure and ejection fraction. Moreover, 5-HTP enhanced mitochondrial respiratory function, as shown by the O2k mitochondrial function assay, by improving mitochondrial complex activity and ATP production. Importantly, the cardioprotective benefits of 5-HTP did not interfere with DOX's ability to combat cancer. These findings shed light on the cardiotoxic mechanisms of DOX and suggest that 5-HTP could be a viable strategy to prevent heart damage during chemotherapy, offering a foundation for future clinical development. This research opens the door for 5-HTP to be considered a dual-purpose agent that can protect the heart without compromising the oncological efficacy of anthracycline chemotherapy.

PROTAC-biomacromolecule conjugates for precise protein degradation in cancer therapy: A review.

Proteolysis targeting chimera (PROTAC) technology is a promising new mode of targeted protein degradation with significant transformative implications for the clinical treatment of different diseases. Nevertheless, while this technology offers numerous advantages, on-target off-tumour toxicity in healthy cells remains a major challenge for clinical application in cancer therapy. Strategies are presently being explored to optimize degradation activity with cellular selectivity to minimize undesirable side effects. PROTAC-antibody conjugates and PROTAC-aptamer conjugates are unique innovations that combine PROTACs and biomacromolecules. These novel PROTAC-biomacromolecule conjugates (PBCs) can enhance the targetability of PROTACs and reduce their off-target side-effects. The combination of potent PROTACs and highly safe biomacromolecules will pioneer an emerging trend in targeted protein degradation. In our review, we have summarized recent advances in PBCs, discussed current challenges, and outlooked opportunities for future research in the field.

The development of biosensors for alkaline phosphatase activity detection based on a phosphorylated DNA probe.

Alkaline phosphatase (ALP) is a zinc-containing metalloprotein that shows very great significance in clinical diagnosis, which can catalyze the hydrolysis of phosphorylated species. ALP has the potential to serve as a valuable biomarker for detecting liver dysfunction and bone diseases. On the other hand, ALP is an efficient biocatalyst to amplify detection signals in the enzyme-linked assay. It has always been a major research focus to develop novel biosensors that can detect ALP activity with high selectivity and sensitivity. There have been numerous reports on the development of biosensors to determine ALP activity using a phosphorylated DNA probe. Among them, various beneficial strategies, such as λ exonuclease-mediated cleavage reaction, terminal deoxynucleotidyl transferase-triggered DNA polymerization, and Klenow fragment polymerase-catalyzed elongation, are employed to generate amplified and more intuitive signal. This review discusses and summarizes the development and advances of biosensors for ALP activity detection that use a well-designed phosphorylated DNA probe, aiming to provide some guidelines for the design of more sophisticated sensing strategies that exhibit improved sensitivity, selectivity, and adaptability in detecting ALP activity.

Advanced function, design and application of skin substitutes for skin regeneration.

The development of skin substitutes aims to replace, mimic, or improve the functions of human skin, regenerate damaged skin tissue, and replace or enhance skin function. This includes artificial skin, scaffolds or devices designed for treatment, imitation, or improvement of skin function in wounds and injuries. Therefore, tremendous efforts have been made to develop functional skin substitutes. However, there is still few reports systematically discuss the relationship between the advanced function and design requirements. In this paper, we review the classification, functions, and design requirements of artificial skin or skin substitutes. Different manufacturing strategies for skin substitutes such as hydrogels, 3D/4D printing, electrospinning, microfluidics are summarized. This review also introduces currently available skin substitutes in clinical trials and on the market and the related regulatory requirements. Finally, the prospects and challenges of skin substitutes in the field of tissue engineering are discussed.

Design, synthesis, and bioevaluation of 1h-pyrrolo[3,2-c]pyridine derivatives as colchicine-binding site inhibitors with potent anticancer activities.

A new series of 1H-pyrrolo[3,2-c]pyridine derivatives were designed and synthesised as colchicine-binding site inhibitors. Preliminary biological evaluations showed that most of the target compounds displayed moderate to excellent antitumor activities against three cancer cell lines (HeLa, SGC-7901, and MCF-7) in vitro. Among them, 10t exhibited the most potent activities against three cancer cell lines with IC50 values ranging from 0.12 to 0.21 µM. Tubulin polymerisation experiments indicated that 10t potently inhibited tubulin polymerisation at concentrations of 3 µM and 5 µM, and immunostaining assays revealed that 10t remarkably disrupted tubulin microtubule dynamics at a concentration of 0.12 µM. Furthermore, cell cycle studies and cell apoptosis analyses demonstrated that 10t at concentrations of 0.12 µM, 0.24 µM, and 0.36 µM significantly caused G2/M phase cell cycle arrest and apoptosis. The results of molecular modelling studies suggested that 10t interacts with tubulin by forming hydrogen bonds with colchicine sites Thrα179 and Asnß349. In addition, the prediction of physicochemical properties disclosed that 10t conformed well to the Lipinski's rule of five.

The role of TNC in atherosclerosis and drug development opportunities.

Tenascin C (TNC), a rich glycoprotein of the extracellular matrix, exhibits a pro-atherosclerosis or anti-atherosclerosis effect depending on its location. TNC, especially its C domain/isoform (TNC-C), is strongly overexpressed in atherosclerotic plaque active areas but virtually undetectable in most normal adult tissues, suggesting that TNC is a promising delivery vector target for atherosclerosis-targeted drugs. Many delivery vectors were investigated by recognizing TNC-C, including G11, G11-iRGD, TN11, PL1, and PL3. F16 and FNLM were also investigated by recognizing TNC-A1 and TNC, respectively. Notably, iRGD was undergoing clinical trials. PL1 not only recognizes TNC-C but also the extra domain-B (EDB) of fibronectin (FN), which is also a promising delivery vector for atherosclerosis-targeted drugs, and several conjugate agents are undergoing clinical trials. The F16-conjugate agent F16IL2 is undergoing clinical trials. Therefore, G11-iRGD, PL1, and F16 have great development value. Furthermore, ATN-RNA and IMA950 were investigated in clinical trials as therapeutic drugs and vaccines by targeting TNC, respectively. Therefore, targeting TNC could greatly improve the success rate of atherosclerosis-targeted drugs and/or specific drug development. This review discussed the role of TNC in atherosclerosis, atherosclerosis-targeted drug delivery vectors, and agent development to provide knowledge for drug development targeting TNC.

The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7.

Atherosclerosis is one of the leading causes of death worldwide. miR-26 is a potential biomarker of atherosclerosis. Standardized diagnostic tests for miR-26 (MIR26-DX) have been developed, but the fastest progress has been in predicting the efficacy of IFN-α therapy for hepatocellular carcinoma (HCC, phase 3). MiR-26 slows atherosclerosis development by suppressing ACC1/2, ACLY, ACSL3/4, ALDH3A2, ALPL, BMP2, CD36, COL1A1, CPT1A, CTGF, DGAT2, EHHADH, FAS, FBP1, GATA4, GSK3ß, G6PC, Gys2, HMGA1, HMGB1, LDLR, LIPC, IL-1ß, IL-6, JAG2, KCNJ2, MALT1, ß-MHC, NF-κB, PCK1, PLCß1, PYGL, RUNX2, SCD1, SMAD1/4/5/7, SREBF1, TAB3, TAK1, TCF7L2, and TNF-α expression. Many agents targeting these genes, such as the ACC1/2 inhibitors GS-0976, PF-05221304, and MK-4074; the DGAT2 inhibitors IONIS-DGAT2Rx, PF-06427878, PF-0685571, and PF-07202954; the COL1A1 inhibitor HT-100; the stimulants 68Ga-CBP8 and RCT-01; the CPT1A inhibitors etomoxir, perhexiline, and teglicar; the FBP1 inhibitors CS-917 and MB07803; and the SMAD7 inhibitor mongersen, have been investigated in clinical trials. Interestingly, miR-26 better reduced intima-media thickness (IMT) than PCSK9 or CT-1 knockout. Many PCSK9 inhibitors, including alirocumab, evolocumab, inclisiran, AZD8233, Civi-007, MK-0616, and LIB003, have been investigated in clinical trials. Recombinant CT-1 was also investigated in clinical trials. Therefore, miR-26 is a promising target for agent development. miR-26 promotes foam cell formation by reducing ABCA1 and ARL4C expression. Multiple materials can be used to deliver miR-26, but it is unclear which material is most suitable for mass production and clinical applications. This review focuses on the potential use of miR-26 in treating atherosclerosis to support the development of agents targeting it.