Burn infection is one of the commonest causes of death in severely burned patients. Developing multifunctional biological nanomaterials has a great significance for the comprehensive treatment of burn infection. In this paper, we developed a hydrogel-based nanodelivery system with antibacterial activity and skin regeneration function, which was used for photodynamic antimicrobial chemotherapy (PACT) in the treatment of burns. The treatment system is mainly composed of porphyrin photosensitizer sinoporphyrin sodium (DVDMS) and poly(lactic-co-glycolic acid) (PLGA)-encapsulated basic fibroblast growth factor (bFGF) nanospheres that are embedded in carboxymethyl chitosan (CMCS)−sodium alginate to form CSDP hybrid hydrogel. We systematically evaluated the inherent antibacterial performance, rheological properties, fluorescence imaging, and biocompatibility of the CSDP nanosystem. Under mild photoirradiation (30 J/cm 2 , 5 min), 10 μg/mL CSDP showed excellent antibacterial and anti-biofilm activities, which eradicated almost 99.99% of Staphylococcus aureus and multidrug-resistant (MDR) S. aureus in vitro. KEGG analysis identified that multiple signaling pathways were changed in MDR S. aureus after PACT. In the burninfection model, CSDP-PACT successfully inhibited bacteria growth and concurrently promoted wound healing. Moreover, several regenerative factors were increased and some proinflammatory factors were reduced in the burn wounds of CSDP hydrogel treatment. These results suggest that the multifunctional CSDP hydrogel is a portable, light-triggered, antibacterial theranosticplatform and CSDP-PACT provides a promising strategy or the mechanically based synergistic treatment of burn infections.
Background and objectives
Antibiotic resistance has emerged as one of the most important determinants of outcome in patients with serious infections, along with the virulence of the underlying pathogen. Photodynamic antimicrobial chemotherapy (PACT) has been proposed as an alternative approach for the inactivation of bacteria. This study aims to evaluate the antibacterial effect of sinoporphyrin sodium (DVDMS)-mediated PACT on
Staphylococcus aureus
and multidrug resistant
S. aureus
in vitro and in vivo.
Materials and methods
Bacteria were incubated with DVDMS and exposed to treatment with light. After PACT treatment, colony-forming units were counted to estimate the bactericidal effect. Intracellular reactive oxygen-species production was detected by flow cytometry. Flow cytometry and fluorescence-microscopy detection of bacterial cell-membrane permeability. Enzyme-linked immunosorbent assays were used to determine expression of VEGF, TGFβ
1
, TNFα, IL6, and bFGF factors in burn infection.
Results
DVDMS-PACT effectively killed bacterial proliferation. Intracellular ROS levels were enhanced obviously in the PACT-treatment group. SYTO 9 and propidium iodide staining showed a decrease in the ratio of green:red fluorescence intensity in the PACT-treatment group in comparison to the control group. Enzyme-linked immunosorbent-assay results revealed that in the healing process, the expression of bFGF, TGFβ
1
, and VEGF in the treatment group were higher than in the control group, which inhibited inflammation-factor secretion. In addition, skin-tissue bacteria were reduced after treatment.
Conclusion
These results indicate that DVDMS-PACT presents significant bactericidal activity and promotes wound healing after burn infections.
An efficient and available material for promoting skin regeneration is of great importance for public health, but it remains an elusive goal. Inspired by fetal scarless wound healing, we develop a wearable biomimetic film (WBMF) composed of hyaluronan (HA), vitamin E (VE), dopamine (DA), and βcyclodextrin (β-CD) that mimics the fetal context (FC) and fetal extracellular matrix (ECM) around the wound bed for dermal regeneration. First, the WBMF creates the FC of sterility, hypoxia, persistent moisture, and no secondary insults for wounds as the result of its seamless adhesion to the skin, optimum stress− stretch and high-cycle fatigue resistance matching the anisotropic tension of the skin, and water-triggered self-healing behavior. Thus, the WBMF modulates the early wound situation to minimize inflammatory response. In the meantime, the WBMF mimics the critical biological function of fetal ECM, inducing fibroblast migration, suppressing the overexpression of transforming growth factor β1, and mediating collagen synthesis, distribution, and reestablishment. As a result, the WBMF accelerates wound healing and gains a normal dermal collagen architecture, thereby restoring scarless appearance. Overall, the WBMF provides a new paradigm for promoting skin wound healing and may find broad utility for the field of regenerative medicine.
Both photodynamic therapy (PDT) and sonodynamic therapy (SDT) are fast growing activated therapies by using light or ultrasound to initiate catalytic reaction of sensitizing agents, showing great potentials in clinics because of high safety and noninvasiveness. Sensitizers are critical components in PDT and SDT. Sinoporphyrin sodium (DVDMS) is an effective constituent derived from Photofrin that has been approved by FDA. This review is based on previous articles that explore the applications of DVDMS mediated photodynamic/sonodynamic cancer therapy and antimicrobial chemotherapy. Researchers utilize different cell lines, distinct treatment protocols to explore the enhanced therapeutic response of neoplastic lesion. Moreover, by designing a series of nanoparticles for loading DVDMS to improve the cellular uptake and antitumor efficacy of PDT/SDT, which integrates diagnostics into therapeutics for precision medical applications. During the sono-/photo-activated process, the balance between oxidation and antioxidation, numerous signal transduction and cell death pathways are also involved. In addition, DVDMS mediated photodynamic antimicrobial chemotherapy (PACT) can effectively suppress bacteria and multidrug resistant bacteria proliferation, promote the healing of wounds in burn infection. In brief, these efficient preclinical studies indicate a good promise for DVDMS application in the activated sono-/photo-therapy.
Increasing
threats from both pathogenic infections and antibiotic
resistance highlight the pressing demand for nonantibiotic agents
and alternative therapies. Herein, we report several new phenothiazinium-based
derivatives, which could be readily synthesized via fragment-based
assembly, which exhibited remarkable bactericidal activities both
in vitro and in vivo. Importantly, in contrast to numerous clinically
and preclinically used antibacterial photosensitizers, these compounds
were able to eliminate various types of microorganisms, including
Gram-(+) Staphylococcus aureus (S. aureus), Gram-(−) Escherichia
coli, multidrug-resistant S. aureus, and their associated biofilms, at low drug and light dosages (e.g.,
0.21 ng/mL in vitro and 1.63 ng/cm2 in vivo to eradicate S. aureus at 30 J/cm2). This study thus
unveils the potential of these novel phenothiaziniums as potent antimicrobial
agents for highly efficient photodynamic antibacterial chemotherapy.
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