Multivalent Phthalocyanine-Based Cationic Polymers with Enhanced Photodynamic Activity for the Bacterial Capture and Bacteria-Infected Wound Healing.

The solubility and photosensitive activity of phthalocyanine are crucial to photodynamic antibacterial performance. However, highly conjugated phthalocyanine with high singlet oxygen generation efficiency tends to aggregate in aqueous environments, leading to poor solubility and photodynamic antibacterial activity. Herein, we propose a novel photodynamic antibacterial therapeutic platform by a phthalocyanine-based polymeric photosensitizer for the efficient healing of a bacteria-infected wound. A prepared phthalocyanine-based chain-transfer agent and a tertiary amino group-containing monomer are applied in the reversible addition-fragmentation chain-transfer polymerization for the preparation of the polymeric photosensitizer, which is subsequently quaternized to obtain a positively charged surface. This water-soluble phthalocyanine-based polymer can strongly concentrate on bacterial membranes via electrostatic interaction. The formed singlet oxygen by the phthalocyanine-based polymer after 680 nm light irradiation plays an essential role in killing the Gram-positive and Gram-negative bacteria. The study of antibacterial action indicates that this nanocomposite can cause irreversible damage to the bacterial membranes, which can cause cytoplasm leakage and bacterial death. Moreover, this therapeutic platform has excellent biocompatibility and the capacity to heal the wounds of bacterial infections. Experimental results indicate that the design strategy of this phthalocyanine-based polymer can extend the application of the hydrophobic photosensitizer in the biomedical field.

The potential application of strategic released apigenin from polymeric carrier in pulmonary fibrosis.

AIM: The capability of reducing fibrotic and inflammatory responses in lung tissues represents a gold standard for evaluating the efficacy of therapeutic interventions for treating idiopathic pulmonary fibrosis (IPF). A wide variety of therapeutic strategies have been employed in clinic to treat PF, but limited success has been obtained. Apigenin (4, 5, 7-trihydroxyflavone) is a member of flavonoid family that exerts anti-inflammatory and anti-fibrosis effects. In this study, we explore the potential therapeutic effect of apigenin in lung fibrosis. MATERIALS AND METHODS: Apigenin was employed to treat IPF in a bleomycin-induced PF rat model. Apigenin was loaded onto a biodegradable polymer carrier (nanoparticle, NP) to improve its bio-solubility and bio-availability. The properties (e.g. size, apigenin loading and release profile) of the apigenin loaded polymer carrier were well-characterized. In vitro study was performed to assess the impact of apigenin on pulmonary cell viability, growth, as well as inflammatory and pro-fibrosis responses in pulmonary cells. The impact of apigenin on the production of inflammatory cytokines (e.g. TGF-ß, TNF-α) and pro-fibrosis factors in bronchoalveolar lavage fluid and pulmonary cells from lung tissues was also investigated. RESULTS: Our results showed, apigenin has anti-fibrosis effect by inhibition fibrosis related cytokines expression. And compared with apigenin in soluble form, the strategic release of apigenin is more effective in inhibiting pulmonary fibrosis and inflammation. CONCLUSION: Our finding suggested that apigenin loaded on polymeric carrier might be an effective treatment for pulmonary fibrosis patients.

Anti-Tumor and Anti-Metastasis Effects of Berbamine-Loaded Lipid Nanoparticles on Pancreatic Cancer.

OBJECTIVE: The aim of the study was to investigate the therapeutic potential of Berbamine-loaded lipid nanoparticles (BBM-NPs) in pancreatic cancer. METHODS: Dopamine polymerization-polylactide-TPGS nanoparticles were synthesized to prepare BBM-NPs, and the change in particle size of BBM-NPs was measured. Cell Counting Kit-8 (CCK8) assay, plate cloning experiment, and apoptosis analysis were performed to evaluate the cytotoxicity of BBM-NPs against the pancreatic cancer cells (PANC-1 and AsPC-1). Migration and invasion abilities of the tumor cells were determined by Transwell and wound healing assays. The intracellular level of ROS and expression of tumor progression-related proteins were measured using ROS-kit and western blot assay. Besides, an in vivo study was performed in the Balb/c nude mice to analyze the function of BBM-NPs in tumor growth. RESULTS: The in vitro studies showed that BBM-NPs with stable particle size and sustained drug release effectively inhibited the viability, proliferation, migration, and invasion of pancreatic cancer cells, while promoting cell apoptosis. Moreover, the in vivo experiments revealed that compared to Free BBM, BBM-NPs exhibited a stronger inhibitory effect on the growth of xenograft tumors derived from PANC-1 cells in mice. In addition, increased expressions of ROS, Bax, Cleaved Caspase-3, and γ-H2AX, as well as decreased expressions of MMP2, MMP9 and Bcl-2 were identified in both Free BBM and BBM-NPs groups, while BBM-NPs exhibited a stronger effect on protein expression than Free BBM. CONCLUSION: In summary, BBM-loaded lipid nanoparticles enhanced the therapeutic effects of BBM on pancreatic cancer, providing a promising strategy for targeted cancer therapy.

PEGylated Phthalocyanine-Functionalized Graphene Oxide with Ultrahigh-Efficient Photothermal Performance for Triple-Mode Antibacterial Therapy.

This study proposes a novel multifunctional synergistic antibacterial phototherapy technique for the rapid healing of bacteria-infected wounds. By binding PEGylated phthalocyanines to the surface of graphene oxide via noncovalent functionalization, the photothermal conversion efficiency of the obtained nanocomposites can be significantly increased, which shows that the sample temperature can achieve nearly 100 °C after only 10 min of 450 nm light illumination at a concentration ≥25 µg/mL. Moreover, the nanocomposites can rapidly generate singlet oxygen under 680 nm light irradiation and physically cut bacterial cell membranes. The triple effects are expected to obtain a synergistic antibacterial efficiency and reduce the emergence of bacterial resistance. After dual-light irradiation for 10 min, the generation of hyperthermia and singlet oxygen can cause the death of Gram-positive and Gram-negative bacteria. The results of an in vivo experiment revealed that the as-prepared nanocomposites combined with dual-light-triggered antibacterial therapy can effectively restrain the inflammatory reaction and accelerate the healing of bacteria-infected wounds. These were confirmed by the examination of pathological tissue sections and inflammatory factors in rats with bacteria-infected wounds. This nanotherapeutic platform is a potential photoactivated antimicrobial strategy for the prevention and treatment of bacterial infection.