Zwitterionic meso-silica/polypeptide hybrid nanoparticles for efficient azithromycin delivery and photodynamic therapy for synergistic treatment of drug-resistant bacterial infection.

The treatment of drug-resistant bacterial infections attributed to the overuse of antibiotics still remains a serious challenge globally. Herein, zwitterionic charge switchable meso-silica/polypeptide hybrid nanoparticles (MSPNs) were prepared for the synergistic chemo-photodynamic therapy in the treatment of drug-resistant bacterial infections. Subsequently, azithromycin (AZT) and methylene blue (MB) were loaded in the MSPNs to form the combined chemo-photodynamic therapeutic nanoparticles (MSPNs-AZT/MB) for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Remarkably, the as-prepared MSPNs-AZT/MB exhibited a negative surface charge of -5.2 mV at physiological pH while switching into positive surface charge of 24.7 mv in an acidic environment, leading to enhanced binding with bacterial surface. The lipase-triggered AZT release up to 77.9 % was achieved, and the loaded MB demonstrated efficient singlet oxygen (1O2) generation for photodynamic therapy. The in vitro experimental results displayed an excellent antibacterial effect against MRSA in both planktonic and biofilm phenotypes. Additionally, the as-prepared MSPNs-AZT/MB exhibited synergistic and enhanced antibacterial infection effect up to 94 % comparing to monotherapy in a mice model. Considering the above advantages, the as-prepared combined chemo-photodynamic therapeutic nanoparticles showed promising biocompatibility and clinical potential for the efficient therapy of drug-resistant bacteria.

Gold nanorods conjugated with biocompatible zwitterionic polypeptide for combined chemo-photothermal therapy of cervical cancer.

Combined chemo-photothermal therapy of gold nanorods (GNRs) for cancer treatment shows better therapeutic efficiency than mono-chemotherapy, which has gained worldwide interests of scientists and clinician in both laboratory and clinic application. However, high cytotoxicity, declined delivery efficiency, and unsatisfactory therapy effect of the GNRs are still challenging in anti-cancer treatment. Herein, a series of pH-sensitively zwitterionic polypeptide conjugated GNRs were synthesized via a gold-thiol interaction for combination of chemo-photothermal therapy in cervical cancer treatment. The acid-labile hydrazone bond was utilized to incorporate the doxorubicin (DOX) for pH-sensitive drug release under tumoral environment. The as prepared GNRs conjugates demonstrated pH-triggered surface charge conversion from negative to positive when transporting from blood circulation to tumor extracellular environment, which can facilitate the cellular uptake via electrostatic interaction. After cellular internalization, the drug release was promoted by cleavage of the hydrazone in GNRs conjugates under cancer intracellular acid environment. As the effective near-infrared (NIR) photothermal materials, the as prepared GNRs conjugates can absorb NIR photo energy and convert it into heat under irradiation, which can efficiently kill the tumor cells. In cell assay, the GNRs conjugates displayed excellent biocompatibility against normal cell, enhanced cancer cell uptake, and remarkable cancer cell killing effects. In HeLa tumor-bearing mice, the GNRs conjugates demonstrated enhanced tumor inhibition efficacy by combination of chemo-photothermal therapy.