Stimuli-Responsive Nanotechnology for RNA Delivery.

Ribonucleic acid (RNA) drugs have shown promising therapeutic effects for various diseases in clinical and preclinical studies, owing to their capability to regulate the expression of genes of interest or control protein synthesis. Different strategies, such as chemical modification, ligand conjugation, and nanotechnology, have contributed to the successful clinical translation of RNA medicine, including small interfering RNA (siRNA) for gene silencing and messenger RNA (mRNA) for vaccine development. Among these, nanotechnology can protect RNAs from enzymatic degradation, increase cellular uptake and cytosolic transportation, prolong systemic circulation, and improve tissue/cell targeting.

ROS-Responsive Nanoparticle Delivery of mRNA and Photosensitizer for Combinatorial Cancer Therapy.

Messenger RNA (mRNA) therapy has shown tremendous potential for different diseases including cancer. While mRNA has been extensively used in cancer vaccine development as antigen or in cancer immunotherapy as immunomodulatory agent, the combination of mRNA therapy with photodynamic therapy has not been explored in cancer treatment. Herein, we report a reactive oxygen species (ROS)-responsive polymeric nanoparticle (NP) platform for first-in-field codelivery of mRNA and photosensitizer for effective cancer treatment.

Combining p53 mRNA nanotherapy with immune checkpoint blockade reprograms the immune microenvironment for effective cancer therapy.

Immunotherapy with immune checkpoint blockade (ICB) has shown limited benefits in hepatocellular carcinoma (HCC) and other cancers, mediated in part by the immunosuppressive tumor microenvironment (TME). As p53 loss of function may play a role in immunosuppression, we herein examine the effects of restoring p53 expression on the immune TME and ICB efficacy. We develop and optimize a CXCR4-targeted mRNA nanoparticle platform to effectively induce p53 expression in HCC models.

A Second Near-Infrared Ru(II) Polypyridyl Complex for Synergistic Chemo-Photothermal Therapy.

The clinical success of cisplatin ushered in a new era of the application of metallodrugs. When it comes to practice, however, drug resistance, tumor recurrence, and drug systemic toxicity make it implausible to completely heal the patients. Herein, we successfully transform an electron acceptor [1, 2, 5]thiadiazolo[3,4-]quinoxaline into a novel second near-infrared (NIR-II) fluorophore .

Site-Specific Biomimicry of Antioxidative Melanin Formation and Its Application for Acute Liver Injury Therapy and Imaging.

Biocompatible nano-antioxidants composed of natural molecules/materials, such as dopamine and melanin, are of great interest for diverse biomedical applications. However, the lack of understanding of the precise structure of these biomaterials and thus the actual dose of effective components impedes their advancement to translation. Herein, a strategy to mimic in situ melanin formation and explore its antioxidative applications is reported, by developing a PEGylated, phenylboronic-acid-protected L-DOPA precursor (PAD) that can self-assemble into well-defined nanoparticles (PADN).

Oxidative-Species-Selective Materials for Diagnostic and Therapeutic Applications.

With the increasing recognition of the diverse roles and significance of oxidative species in the pathogenesis of many diseases, a tremendous amount of work on the development of oxidative-species-responsive materials has been conducted for 1) detecting oxygen metabolites or diagnosis of oxidative-stress-relevant diseases, 2) reducing oxidative stress in the disease sites, and/or 3) delivering therapeutic and diagnostic agents. In this review, we first discuss the distinct features and biological functions of each oxidative species. Then the selectivity and sensitivity of chemical linkers/groups to specific oxidative species and the underlying chemistry of their particular interactions are systematically elucidated.