A wide array of biocompatible micro/nanorobots are designed for targeted drug delivery and precision therapy largely depending on their self-adaptive ability overcoming complex barriers in vivo. Here, we report a twin-bioengine yeast micro/nanorobot (TBY-robot) with self-propelling and self-adaptive capabilities that can autonomously navigate to inflamed sites for gastrointestinal inflammation therapy via enzyme-macrophage switching (EMS). Asymmetrical TBY-robots effectively penetrated the mucus barrier and notably enhanced their intestinal retention using a dual enzyme-driven engine toward enteral glucose gradient. Thereafter, the TBY-robot was transferred to Peyer’s patch, where the enzyme-driven engine switched in situ to macrophage bioengine and was subsequently relayed to inflamed sites along a chemokine gradient. Encouragingly, EMS-based delivery increased drug accumulation at the diseased site by approximately 1000-fold, markedly attenuating inflammation and ameliorating disease pathology in mouse models of colitis and gastric ulcers. These self-adaptive TBY-robots represent a safe and promising strategy for the precision treatment of gastrointestinal inflammation and other inflammatory diseases.

Abastract: Plasmonic nanomaterials, especially a wide variety of gold nanoparticles, demonstrate great potential for theranostics of cancer. Herein, a gold nanotriangle with CD133 and hyaluronic acid on its surface loaded with a near-infrared photosensitizer was prepared for enhanced photodynamic/photothermal combined anti-tumor therapy. CD133 and hyaluronic acid provide the nanoprobe with dual tumor targeting, while the hyaluronic acid also protects photosensitive drugs from photodegradation. Thus, the nanoprobe has enhanced photothermal/photodynamic effects. This integrated treatment strategy significantly enhanced photodynamic/photothermal destruction of osteosarcoma cells. In addition, this treatment, induced by mild irradiation with a single wavelength laser, inhibited tumor growth in an osteosarcoma mouse model. These results indicate that this systemic treatment strategy can achieve enhanced anti-tumor therapeutic effects through active tumor targeting and protection of the loaded drugs.

Manganese (Mn)-based materials have been extensively investigated for a wide range of biomedical applications owing to their remarkable catalytic chemistry, magnetic resonance imaging (MRI) capacity, biodegradability, low toxicity, and good biosafety. In this review, we first elaborate on the catalytic principle of Mn-based nanoenzymes for antitumor and antibacterial therapy, followed by a comprehensive discussion of the interesting structural design engineering strategies used to achieve multi-dimensional Mn-based nanoarchitectures, such as zero-dimensional (0D) nanoparticles, 1D nanotubes, 2D nanosheets, 3D hollow porous Mn ball, and core–shell nanostructures. Moreover, the therapeutic applications of different Mn-based nanoenzymes, including manganese dioxide (MnO₂)-based nanoenzymes that can trigger catalytic reactions, Mn²⁺-doped metal nanoenzymes and Mn²⁺-coordinated nanoenzymes that promote hydroxyl/reactive oxygen species (ROS) generation, and MnO₂-based micro/nanorobots that can effectively penetrate tumor tissues, are critically reviewed. Finally, a brief overview of the potential challenges faced in the development of Mn-based nanoenzymes is presented, along with a comparative and balanced discussion of future prospects.

Metal nanoenzymes (HMnO₂@CDDP) that can degrade to produce Mn²⁺ exhibit Fenton-like, GSH-peroxidase-like activity. Treatment with nanoenzymes increased intratumor Pt-DNA content, leading to the up-regulation of γ-H2Aχ and an increase in tumor damage.

Sonodynamic therapy (SDT), as a novel cancer therapy strategy, might be a promising approach due to the depth-penetration property in tissue. Sonosensitizers are the key element for efficient SDT. However, the development of sonosensitizers with strong sonosensitization efficacy is still a significant challenge. Herein, an urchin-shaped copper-based metalloporphyrin liposome nanosystem (FA–L–CuPP) is constructed and identified as an excellent sonosensitizer. Under ultrasound (US) irradiation, FA–L–CuPP can be highly excited to generate several reactive oxygen species (ROS), such as singlet oxygen (¹O₂) and free radicals (⋅OH). The molecular orbital distribution calculations reveal that a strong intramolecular charge transfer might occur in the CuPP complex under US irradiation, which could afford enough energy to the surrounding O₂ and H₂O to concert ¹O₂, O₂⁻ and ⋅OH. Working as “ammunitions”, the largely produced ROS can kill 4T1 tumor cells, effectively inhibiting tumor growth. This work provides an urchin-shaped nanosonosensitizer based on a copper complex, which might provide an idea to design a novel sonosensitizer for noninvasive and precise SDT antitumor applications.

OV/M nanovesicles infected azido-labelled tumor tissues specifically by bioorthogonal targeting and homologous recognition. This strategy reshaped the tumor microenvironment significantly, achieving combination bio-immunotherapy with CAR-T cells.