The role and mechanism of polydopamine and cuttlefish ink melanin carrying copper ion nanoparticles in antibacterial properties and promoting wound healing.

Melanin and its analogue polydopamine (PDA) have attracted considerable attention in biomedical science due to their surface-rich metal binding sites, excellent adhesion and good biocompatibility. Bacterial infections at the wound site and uncontrolled bleeding are associated with a high risk of death, and the prevention of wound infections remains a major challenge. On this basis, the four nanoparticles (NPs) of melanin, PDA, copper ion-loaded melanin (Cu(ii) loaded melanin) and copper ion-loaded PDA (Cu(ii) loaded PDA) were studied in terms of antibacterial and wound healing capabilities. The in vitro experiments showed that Cu(ii) loaded PDA NPs had good blood compatibility and low cytotoxicity, showing the best antibacterial effect in comparison with other samples. Not only could the slow release of copper ions from the nanoparticles kill bacteria, but also the phenolic hydroxyl group and amine groups of PDA NPs played a synergistic role in bacterial death. In wound healing experiments, the Cu(ii) loaded PDA NPs could easily and tightly bind with biological tissue, demonstrating excellent hemostasis, antibacterial and wound healing capabilities. In summary, the excellent properties of Cu(ii) loaded PDA NPs made them a safe and effective drug for preventing wound infection and promoting healing.

Fe2+/Fe3+ Ions Chelated with Ultrasmall Polydopamine Nanoparticles Induce Ferroptosis for Cancer Therapy.

Ferroptosis, a promising mechanism of killing cancer cells, has become a research hotspot in cancer therapy. Besides, advantages of polymeric nanomaterials in improving anticancer efficacy and reducing side effect are widely accepted. In this work, based on the property of polypodamine to chelate metal ions, ultrasmall poly(ethylene glycol)-modified polydopamine nanoparticles, (UPDA-PEG)@Fe2+/3+ nanoparticles, a novel ferroptosis agent, was rationally designed by chelating iron ions on ultrasmall polydopamine nanoparticles modified by PEG. This treatment led to a bigger specific surface area, which could support more reactive sites to chelate large number of iron ions, which is beneficial for exploring the detailed mechanism of ferroptosis-induced tumor cell death by iron ions. Also, the pH-dependent release of iron ions can reach approximately 70% at pH 5.0, providing the advantage of application in tumor microenvironment. The in vitro tests showed that the as-prepared NPs exhibit an effective anticancer effect on tumor cells including 4T1 and U87MG cells, yet ferric ions show a stronger ability of killing cancer cells than ferrous ions. Differences between ferrous ions and ferric ions in the ferroptosis pathway were monitored by the change of marker, including reactive oxygen species (ROS), glutathione peroxidase 4, and lipid peroxide (LPO), as well as the promoter and inhibitor of ferroptosis pathway. UPDA-PEG@Fe2+ nanoparticles induce ferroptosis that depends more on ROS; however, a more LPO-dependent ferroptosis is induced by UPDA-PEG@Fe3+ nanoparticles. Additionally, the in vivo studies using tumor-bearing Balb/c mice demonstrated that the as-prepared NPs could significantly inhibit tumor progression. UPDA-PEG@Fe2+/3+ nanoparticles reported herein represent the nanoparticles related to iron ions for chemotherapy against cancer through the ferroptosis pathway.

Facile One-Pot Synthesis of Polydopamine Carbon Dots for Photothermal Therapy.

Carbon dots (CDs) are a member of fluorescent carbon nanomaterials that are widely applied in bioimaging, photothermal therapy (PTT), and biosensors for its tunable fluorescence, photothermal conversion property, and excellent biocompatibility. Surface passivation and doping especially the doping of N atoms are critical factors to enhance the fluorescent intensity of CDs. Until now, a variety of nitrogen-rich molecules has been applied for the surface passivation of CDs such as L-Dopa, amino acids, and polyethylenimine (PEI). Herein, we report the synthesis of fluorescent polydopamine (PDA)-passivated carbon dots (CD-PDA) via one-pot microwave-assisted pyrolysis within 5 min, dramatically simplifying the reaction process compared with the hydrothermal treatment reported before. DLS, FT-IR, UV-Vis, and fluorescence spectroscopy were used to confirm the components of CD-PDA and to illuminate the mechanism of its tunable photoluminescence (PL). Due to the doping of N atoms by PDA, quantum yield (QY) of the CD-PDA was measured at 5%, which was nearly triple the original CDs without adding PDA. Yield of CD-PDA was about 1.5 times of the CDs on account of the enhancement of nucleation site for the carbon dot formation with the phenolic group provided by PDA. Meanwhile, photothermal conversion efficiency of the CD-PDA was determined to be 35% because of the excellent NIR light-thermal conversion property of PDA. Overall, we provided an extremely efficient approach to fabricate the fluorescent N-doped CD-PDA with stable photothermal conversion efficiency and excellent biocompatibility. More importantly, the passivation of PDA enabled the CD-PDA synthesized in our research compatible for further modification through Michael addition or Schiff base reaction.