Background: Oxidative stress contributes to retina ganglion cells (RGCs) loss in variety of ocular diseases, including ocular trauma, ocular vein occlusion, and glaucoma. Scavenging the excessed reactive oxygen species (ROS) in retinal neurovascular unit could be beneficial to RGCs survival. In this study, a polydopamine (PDA)-based nanoplatform is developed to protect RGCs. Results: The PDA nanoparticles efficiently eliminate multi-types of ROS, protect endothelia and neuronal cells from oxidative damage, and inhibit microglia activation in retinas. In an optic nerve crush (ONC) model, single intravitreal injection of PDA nanoparticles could significantly attenuate RGCs loss via eliminating ROS in retinas, reducing the inflammatory response and maintaining barrier function of retinal vascular endothelia. Comparative transcriptome analysis of the retina implied that PDA nanoparticles improve RGCs survival probably by altering the expression of genes involved in inflammation and ROS production. Importantly, as a versatile drug carrier, PDA nanoparticles could deliver brimonidine (a neuroprotection drug) to synergistically attenuate RGCs loss and promote axon regeneration, thus restore visual function. Conclusions: The PDA nanoparticle-based therapeutic nanoplatform displayed excellent performance in ROS elimination, providing a promising probability for treating retinal degeneration diseases. Graphical

Cinnamaldehyde, a natural product that can be extracted from a variety of plants of the genus Cinnamomum, exhibits excellent biological activities including antibacterial, antifungal, anti-inflammatory, and anticancer properties. To overcome the disadvantages (e.g., poor water solubility and sensitivity to light) or enhance the advantages (e.g., high reactivity and promoting cellular reactive oxygen species production) of cinnamaldehyde, cinnamaldehyde can be loaded into or conjugated with polymers for sustained or controlled release, thereby prolonging the effective action time of its biological activities. Moreover, when cinnamaldehyde is conjugated with a polymer, it can also introduce environmental responsiveness to the polymer through the form of stimuli-sensitive linkages between its aldehyde group and various functional groups of polymers. The environmental responsiveness provides the great potential of cinnamaldehyde-conjugated polymers for applications in the biomedical field. In this review, the strategies for preparing cinnamaldehyde-contained polymers are summarized and their biomedical applications are also reviewed.

Therapeutic generation of reactive oxygen species (ROS) through catalytic therapy demonstrates antibacterial efficacy against wound infections. However, prolonged and unregulated ROS production risks inducing intolerable oxidative stress alongside exacerbated inflammatory responses, creating a microenvironment counterproductive to wound healing. Here, inspired by rechargeable batteries, we have developed a catalytic activity-controllable nanozyme by integrating Fe(II) and Fe(III) within metal-organic frameworks (FeNZ). Specifically, the overexpressed glutathione in the infective wound can increase the Fe(II) fraction in FeNZ and endow FeNZ with peroxidase (POD)-like activity, which can convert hydrogen peroxide (H2O2) into hydroxyl radicals (•OH) for effective eradication of both drug-sensitive and drug-resistant bacteria (Staphylococcus aureus, 97.9% of antibacterial rate; methicillin-resistant S. aureus (MRSA), 93.2% of antibacterial rate) by disrupting bacterial membranes. Of note, the catalytic performance of FeNZ declined in parallel with the increase in Fe(III) content during the •OH generation process, resulting in a low inflammatory microenvironment for infected wound healing and faster wound healing (95.5% of healing rate for FeNZ + H2O2 group, 83.5% of healing rate for Control group, day 16). The activity-controllable FeNZ thus holds promise as an effective agent for bacterial elimination and enhanced wound repair, presenting a novel strategy for the management of infected wounds.

Traditional chemotherapeutic agents suffer from a lack of selectivity, poor targeting ability, and drug resistance. Developing tumor-specific therapies is crucial for precisely eliminating tumors while circumventing toxicity to normal tissues. Disulfiram (DSF), an FDA-approved drug for treating alcohol dependence, exhibits antitumor effect by forming complexes with copper ions (Cu(DDC)2). Here, we developed a Cu-doped polydopamine-based nanosystem (DSF@CuPDA-PEGM) to achieve in situ generation of toxic Cu(DDC)2. In cancer cells with elevated H2O2 contents, CuPDA responsively degrades to release Cu ions and DSF, allowing on-site synthesis of Cu(DDC)2 with potent antitumor activity. DSF@CuPDA-PEGM exhibits excellent therapeutic efficacy against both drug-sensitive and drug-resistant cancer cells while minimizing toxicity to noncancerous cells. Moreover, DSF@CuPDA-PEGM promotes the immune response by inducing cancer cell immunogenic death, thereby augmenting anti-PD-1-based immune checkpoint blockade therapy. A tumor-specifically degradable Cu-doped polydopamine-based nanosystem is developed to achieve in situ synthesis of antitumor compounds, providing a promising approach to precisely eliminate tumors and heighten chemo-immunotherapy.