Intelligent Generic High-Throughput Oscillatory Shear Technology Fabricates Programmable Microrobots for Real-Time Visual Guidance During Embolization.

Microrobots for endovascular embolization face challenges in precise delivery within dynamic blood vessels. Here, an intelligent generic high-throughput oscillatory shear technology (iGHOST) is proposed to fabricate diversely programmable, multifunctional microrobots capable of real-time visual guidance for in vivo endovascular embolization. Leveraging machine learning (ML), key synthesis parameters affecting the success and sphericity of the microrobots are identified.

Ocular RNA nanomedicine: engineered delivery nanoplatforms in treating eye diseases.

Ocular disorders remain a major global health challenge with unmet medical needs. RNA nanomedicine has shown significant therapeutic benefits and safety profiles in patients with complex eye disorders, already benefiting numerous patients with gene-related eye disorders. The effective delivery of RNA to the unique structure of the eye is challenging owing to RNA instability, off-target effects, and ocular physiological barriers.

Chemically Modified Platforms for Better RNA Therapeutics.

RNA-based therapies have catalyzed a revolutionary transformation in the biomedical landscape, offering unprecedented potential in disease prevention and treatment. However, despite their remarkable achievements, these therapies encounter substantial challenges including low stability, susceptibility to degradation by nucleases, and a prominent negative charge, thereby hindering further development. Chemically modified platforms have emerged as a strategic innovation, focusing on precise alterations either on the RNA moieties or their associated delivery vectors.

Regulatory Fibroblast-Like Synoviocytes Cell Membrane Coated Nanoparticles: A Novel Targeted Therapy for Rheumatoid Arthritis.

Fibroblast-like synoviocytes (FLS) are the main cell component in the inflamed joints of patients with rheumatoid arthritis (RA). FLS intimately interact with infiltrating T cells. Fibroblasts have potent inhibitory effects on T cells, leading to the resolution of inflammation and immune tolerance.

Amplifying Dendritic Cell Activation by Bioinspired Nanometal Organic Frameworks for Synergistic Sonoimmunotherapy.

Despite recent advancements of sonodynamic therapy (SDT) in cancer immunotherapy, challenges have yet to be surmounted to further boost its immunotherapeutic efficacy due to the low-level tumor antigens presentation of dendritic cells (DCs). Cell membrane camouflaged-nanoparticles can integrate the neoantigens of the cancer cell membrane with the multifunctionalities of synthetic nanocores. Herein, sono-responsive nanoparticles coated with DC-targeted antibody chimeric cancer cell membrane are investigated for multimodal therapy.

Bioinspired membrane-based nanomodulators for immunotherapy of autoimmune and infectious diseases.

Autoimmune or infectious diseases often instigate the undesirable damages to tissues or organs to trigger immune-related diseases, which involve plenty of immune cells, pathogens and autoantibodies. Nanomedicine has a great potential in modulating immune system. Particularly, biomimetic nanomodulators can be designed for prevention, diagnosis and therapy to achieve a better targeted immunotherapy.

Functional nanovesicles displaying anti-PD-L1 antibodies for programmed photoimmunotherapy.

Background: Photoimmunotherapy is one of the most promising strategies in tumor immunotherapies, but targeted delivery of photosensitizers and adjuvants to tumors remains a major challenge. Here, as a proof of concept, we describe bone marrow mesenchymal stem cell-derived nanovesicles (NVs) displaying anti-PD-L1 antibodies (aPD-L1) that were genetically engineered for targeted drug delivery.

Results: The high affinity and specificity between aPD-L1 and tumor cells allow aPD-L1 NVs to selectively deliver photosensitizers to cancer tissues and exert potent directed photothermal ablation.

Bioinspired Membrane-Coated Nanoplatform for Targeted Tumor Immunotherapy.

Immunotherapy can effectively activate the immune system and reshape the tumor immune microenvironment, which has been an alternative method in cancer therapy besides surgery, radiotherapy, and chemotherapy. However, the current clinical outcomes are not satisfied due to the lack of targeting of the treatment with some unexpected damages to the human body. Recently, cell membrane-based bioinspired nanoparticles for tumor immunotherapy have attracted much attention because of their superior immune regulating, drug delivery, excellent tumor targeting, and biocompatibility.

Biomimetic nanoparticles blocking autophagy for enhanced chemotherapy and metastasis inhibition via reversing focal adhesion disassembly.

Background: Autophagy is a conserved catabolic process, which plays an important role in regulating tumor cell motility and degrading protein aggregates. Chemotherapy-induced autophagy may lead to tumor distant metastasis and even chemo-insensitivity in the therapy of hepatocellular carcinoma (HCC). Therefore, a vast majority of HCC cases do not produce a significant response to monotherapy with autophagy inhibitors.

Nanotransferrin-Based Programmable Catalysis Mediates Three-Pronged Induction of Oxidative Stress to Enhance Cancer Immunotherapy.

Current oxidative stress amplifying strategies for immunogenic cell death (ICD) promotion are mainly restricted to immune tolerance induced by adaptive cellular antioxidation, limited tumor-selectivity, and tumoral immunosuppression. Herein, a facile and efficient scenario of genetically engineering transferrin-expressing cell membrane nanovesicle encapsulated IR820-dihydroartemisinin nanomedicine (Tf@IR820-DHA) was developed to boost a-PD-L1-mediated immune checkpoint blocking (ICB) synergetic triple stimuli-activated oxidative stress-associated ICD. We demonstrate that the engineered transferrin of Tf@IR820-DHA has excellent tumor targeting and Fe(III)-loading properties and thus delivered Fe(III) and IR820-DHA nanoparticles (NPs) to the lesion location effectively.

Genetically engineered magnetic nanocages for cancer magneto-catalytic theranostics.

The clinical applications of magnetic hyperthermia therapy (MHT) have been largely hindered by the poor magnetic-to-thermal conversion efficiency of MHT agents. Herein, we develop a facile and efficient strategy for engineering encapsulin-produced magnetic iron oxide nanocomposites (eMIONs) via a green biomineralization procedure. We demonstrate that eMIONs have excellent magnetic saturation and remnant magnetization properties, featuring superior magnetic-to-thermal conversion efficiency with an ultrahigh specific absorption rate of 2390 W/g to overcome the critical issues of MHT.

A Self-Assembled α-Synuclein Nanoscavenger for Parkinson's Disease.

Although emerging evidence suggests that the pathogenesis of Parkinson's disease (PD) is closely related to the aggregation of alpha-synuclein (α-syn) in the midbrain, the clearance of α-syn remains an unmet clinical need. Here, we develop a simple and efficient strategy for fabricating the α-syn nanoscavenger for PD a reprecipitation self-assembly procedure. The curcumin analogue-based nanoscavenger (NanoCA) is engineered to be capable of a controlled-release property to stimulate nuclear translocation of the major autophagy regulator, transcription factor EB (TFEB), triggering both autophagy and calcium-dependent exosome secretion for the clearance of α-syn.

TRAIL-expressing cell membrane nanovesicles as an anti-inflammatory platform for rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) is one of the most common chronic autoimmune diseases. Although the progress made with current clinical use of biologic disease-modifying antirheumatic drugs (bioDMARDs), the response rate of RA treatment remains ungratified, primarily due to intricacy interactions of multiple inflammatory cytokines and the awkward drug delivery. Thus, it is of great importance to neutralize cytokines and actively deliver therapeutic agents to RA joints for the purpose of promoting in situ activity.

Oxidative stress-driven DR5 upregulation restores TRAIL/Apo2L sensitivity induced by iron oxide nanoparticles in colorectal cancer.

There exists an emergency clinical demand to overcome TRAIL/Apo2L (tumor necrosis factor-related apoptosis-inducing ligand) resistance, which is a major obstacle attributed to insufficient level or mutation of TRAIL receptors. Here, we developed an iron oxide cluster-based nanoplatform for both sensitization and MR image-guided evaluation to improve TRAIL/Apo2L efficacy in colorectal cancer, which has an inadequate response to TRAIL/Apo2L or chemotherapy. Specifically, NanoTRAIL (TRAIL/Apo2L-iron oxide nanoparticles) generated ROS (reactive oxygen species)-triggered JNK (c-Jun N-terminal kinase) activation and induced subsequent autophagy-assisted DR5 upregulation, resulting in a significant enhanced antitumor efficacy of TRAIL/Apo2L, which confirmed in both TRAIL-resistant HT-29, intermediately resistant SW-480 and sensitive HCT-116 cells.

Photo-excitable hybrid nanocomposites for image-guided photo/TRAIL synergistic cancer therapy.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in cancer cells without toxicity to normal cells. However, the efficiency is greatly limited by its short half-life and wild resistance in various cancer cells. In this study, we reported a micellar hybrid nanoparticle to carry TRAIL ligand (denoted as IPN@TRAIL) for a novel photo-excited TRAIL therapy.

NanoTRAIL-Oncology: A Strategic Approach in Cancer Research and Therapy.

TRAIL is a member of the tumor necrosis factor superfamily that can largely trigger apoptosis in a wide variety of cancer cells, but not in normal cells. However, insufficient exposure to cancer tissues or cells and drug resistance has severely impeded the clinical application of TRAIL. Recently, nanobiotechnology has brought about a revolution in advanced drug delivery for enhanced anticancer therapy using TRAIL.