Esophageal squamous cell carcinoma (ESCC) progression is strongly associated with the overexpression of bromodomain-containing protein 4 (BRD4) and syndecan-binding protein (SDCBP), identifying them as promising therapeutic targets. Conventional inhibitors, however, are frequently constrained by off-target effects and insufficient tumor specificity. Gene therapy, with nucleic acid drugs as its core, offers the advantage of directly modulating disease-causing gene expression, therefore overcoming these limitations. Therefore, this study aims to develop a multifunctional nucleic acid nanohybrid integrating an ESCC-specific aptamer, BRD4 DNAzyme (BDz), and SDCBP DNAzyme (SDz) for tumor-targeted therapy. This nanohybrid is engineered to respond to the acidic lysosomal environment by releasing BDz and SDz, enabling dual gene silencing, while tumor-specific delivery is mediated by the aptamer. Systematic adjustment of the molar ratios of BDz, SDz, and aptamer A components revealed that a 3:2:1 ratio produced optimal antitumor efficacy. This approach establishes a tunable-ratio dual-DNAzyme delivery platform that maximizes synergistic therapeutic effects while balancing targeted delivery with effective gene silencing, achieving precise dual-target therapy against ESCC. The results provide a base for the development of customizable multifunctional precision gene therapies.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive pulmonary disorder characterized by fibrotic scarring, hypoxemia, and dyspnea. Although oxygen therapy is widely used to relieve acute dyspnea, it faces limitations such as oxygen toxicity and patient immobility. To address these challenges, this study developed upconversion-based microrobots capable of mitigating IPF through in situ oxygen generation. These microrobots consist of Chlamydomonas reinhardtii algae functionalized with upconversion nanoparticles. Upon inhalation and exposure to near-infrared light, the microrobots convert the incident light into red visible light, driving photosynthetic oxygen production at a rate of 0.298 ± 0.005 mg·(L·min)⁻¹. Moreover, their autonomous mobility within the mucus enhances the uniformity of oxygen distribution and prolongs retention by evading pulmonary macrophage clearance. In a murine model of IPF, the microrobots effectively alleviated hypoxia, as evidenced by reduced hypoxia-inducible factor 1-alpha (HIF-1α) expression in fibrotic lung tissues and elevated blood oxygen saturation. This platform presents an efficient and promising strategy for oxygen therapy in IPF and broader pulmonary oxygen-dependent applications.

Micro/nanomotors (MNMs) have recently emerged as highly promising drug delivery vehicles, showing great potential for biomedical applications. MNMs are typically classified based on their driving mechanisms, and one notable category is gas-driven MNMs, which are self-propelled at the micro/nano scale by gases generated through chemical reactions. These motors can effectively overcome various physiological barriers by utilizing unique physiological actions and driving forces in vivo, gas-driven MNMs offer significant advantages in treating diseases such as tumors and thrombosis. This review first explores the underlying mechanisms of gas-driven MNMs, then discusses their recent applications in overcoming physiological barriers. Finally, it analyses their future prospects and advantages, aiming to inspire further research and accelerate clinical translation in the biomedical field.

Antisense oligonucleotide (ASO) for anti-apoptosis is emerging as a highly promising therapeutic agents for ischemic stroke with complex pathological environment. However, its therapeutic efficacy is seriously limited by a number of challenges including inefficient internalization, low blood-brain barrier (BBB) penetration, poor stability, and potential toxicity of the carrier. Herein, a carrier-free programmed spherical nucleic acid nanostructure is developed for effective ischemic stroke therapy via integrating multifunctional modules into one DNA structure. By co-encoding caspase-3-ASO and transferrin receptor (TfR) aptamer into circle template, the spherical nucleic acid nanostructure (TD) was obtained via self-assembly. The experimental results demonstrated that the developed TD displayed efficient BBB penetration capability (6.4 times) and satisfactory caspase-3 silence effect (2.3 times) due to the dense DNA packaging in TD. Taken together, our study demonstrated that the carrier-free programmed spherical nucleic acid nanostructure could significantly improve the therapeutic efficacy of ischemic stroke and was a promising therapeutic tool for various brain damage-related diseases.