Drug-resistant bacterial infections pose a serious threat to human public health. Biofilm formation is one of the main factors contributing to the development of bacterial resistance, characterized by a hypoxic and microacidic microenvironment. Traditional antibiotic treatments have been ineffective against multidrug-resistant (MDR) bacteria. Novel monotherapies have had little success. On the basis of the photothermal effect, molybdenum disulfide (MoS2) nanoparticles were used to link quaternized polyethylenimine (QPEI), dihydroporphyrin e6 (Ce6), and Panax notoginseng saponins (PNS) in a zeolitic imidazolate framework-8 (ZIF-8). A multifunctional nanoplatform (MQCP@ZIF-8) was constructed with dual response to pH and near-infrared light (NIR), which resulted in synergistic photothermal and photodynamic antibacterial effects. The nanoplatform exhibited a photothermal conversion efficiency of 56%. It inhibited MDR Escherichia coli (E. coli) and MDR Staphylococcus aureus (S. aureus) by more than 95% and effectively promoted wound healing in mice infected with MDR S. aureus. The nanoplatform induced the death of MDR bacteria by promoting biofilm ablation, disrupting bacterial cell membranes and intracellular DNA, and interfering with intracellular material and energy metabolism. In this study, a multifunctional nanoplatform with good antibacterial effect was developed. The molecular mechanisms of MDR bacteria were also elucidated for possible clinical application.

In order to prevent drugs from being captured and degraded by the acidic environment of organelles, this study designed and prepared a novel carrier amphiphilic polypeptide (DGRHHHLLLAAAA), designated P13, for use as a tumor-targeting drug delivery vehicle.The P13 peptide was prepared by the solid phase synthesis method, and its self-assembly behavior and drug-loading capacity in aqueous solution were studied and characterized in vitro. Doxorubicin (DOX) was loaded by dialysis method, and P13 and DOX were mixed at a mass ratio of 6:1 to form regular rounded globules. The acid-base buffering capacity of P13 was investigated determined by acid-base titration. The results revealed that P13 had excellent acid-base buffering capacity, a critical micelle concentration (CMC) value of about 0.00021g/L, and the particle size of P13-DOX nanospheres was 167 nm, and the zeta potentials of P13-DOX was 24.8 ± 1.0 mV. The drug encapsulation efficiency and drug loading capacity of micelles were 20.40±1.21% and 21.25±2.79%, respectively. At the concentration of 50 μg/mL of P13-DOX , the inhibition rate was 73.35%. The results of the in vivo antitumor activity assay in mice showed that P13-DOX also exhibited excellent inhibitory effect on tumor growth, compared with the tumor weight of 1.1 g in the control group, the tumor weight in the P13-DOX-treated group was only 0.26 g. Additionally, the results of hematoxylin and eosin (H&E) staining of the organs showed that P13-DOX had no damaging effect on normal tissues. The novel amphiphilic peptide P13 with proton sponge effect designed and prepared in this study is expected to be a promising tumor-targeting drug carrier with excellent application potential.

Drug-resistant bacterial infections pose a significant threat to global public health. Furthermore, the formation of biofilms makes traditional antibiotic treatments significantly less effective in killing multidrug-resistant (MDR) bacteria. In this work, we prepared a molybdenum disulfide (MoS2) nanosphere-based nanocomposite that utilized both photothermal therapy (PTT) and chemodynamic therapy (CDT) for effectively eradicating biofilms. A layer of manganese dioxide (MnO2) was adsorbed onto the surface of the MoS2 nanospheres by redox and electrostatic adsorption methods, and the resulting MoS2/MnO2 were loaded with 2,2′-azobis[2-(2-imidazolin-2-yl)propane]-dihydrochloride (AIPH) to form the MoS2/MnO2-AIPH nanocomposite (MMA). The microenvironment of biofilms is slightly acidic, lacks oxygen, and has a high concentration of glutathione (GSH). The MnO2 was capable of reacting with GSH to deplete it while also generating •OH radicals for CDT. In the presence of NIR light (808 nm), the temperature increase brought about by PTT further enhanced the CDT efficacy synergistically. The results showed that the photothermal conversion efficiency of the MMA was 40.5% at a concentration of 100 μg/mL, and the biofilm eradication rate of both MDR Escherichia coli and MDR Staphylococcus aureus was above 90%. The high bacterial inhibition rate (above 96%), as well as the excellent biosafety and biocompatibility of the MMA nanocomposite enabled it to effectively promote wound healing, which has significant implications in treating bacterial infections and promoting wound healing in clinical settings.