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1.
J Mater Chem B ; 10(25): 4878-4888, 2022 06 29.
Article in English | MEDLINE | ID: mdl-35698997

ABSTRACT

Uncontrollable bleeding and infection are two of the most common causes of trauma-related death. Yet, developing safe materials with high hemostatic and antibacterial effectiveness remains a challenge. Keratin-based biomaterials have been reported to exhibit the functions of enhancing platelet binding and activating and facilitating fibrinogen polymerization. In this study, we designed a hemostatic material with good biodegradability, biocompatibility, hemostatic ability, and antibacterial function to solve the shortcomings of common hemostatic materials. Methylene blue-loaded keratin/alginate composite scaffolds were prepared by the freeze-gelation method. The composite scaffolds exhibited over 1600% liquid absorption, well-interconnected pores, good biocompatibility, and biodegradability. We find that the keratin/alginate composite scaffolds' synergistic action may significantly reduce hemostasis time. To prevent infection, the drug-loaded scaffolds generated high burst release by absorbing wound exudate in the early stages of wound healing. The results obtained by the antimicrobial photoinactivation assay in vitro suggest that an antimicrobial photodynamic effect might be triggered, thereby preventing the fast growth of colonies.


Subject(s)
Anti-Infective Agents , Hemostatics , Photochemotherapy , Alginates , Anti-Bacterial Agents/pharmacology , Hemostasis , Hemostatics/pharmacology , Hydrogels/pharmacology , Keratins , Methylene Blue/pharmacology
2.
ACS Appl Mater Interfaces ; 13(32): 38074-38089, 2021 Aug 18.
Article in English | MEDLINE | ID: mdl-34351754

ABSTRACT

Photodynamic therapy (PDT) holds tantalizing prospects of a prominent cancer treatment strategy. However, its efficacy remains limited by virtue of the hypoxic tumor microenvironment and the inadequate tumor-targeted delivery of photosensitizers, and these can be further exacerbated by the lack of development of a well-controlled nitric oxide (NO) release system at the target site. Inspired by Chinese medicine, we propose a revealing new keratin application. Keratin has garnered attention as an NO generator; however, its oncological use has rarely been investigated. We hypothesized that the incorporation of a phenylboronic acid (PBA) targeting ligand/methylene blue (MB) photosensitizer with a keratin NO donor would facilitate precise tumor delivery, enhancing PDT. Herein, we demonstrated that MB@keratin/PBA/d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) nanoparticles (MB@KPTNPs) specifically targeted breast cancer cells and effectively suppressed their growth. Through MB-mediated biometabolism, the endocytic MB@KPTNPs produced a sufficient amount of intracellular NO that reduced the glutathione level while boosting the efficiency of PDT. A therapeutic combination of NO/PDT was therefore achieved, resulting in significant inhibition of both in vivo tumor growth and lung metastasis. These findings underscore the importance of utilizing keratin-based nanoparticles that simultaneously combine targeting of the tumor and self-generating NO with a cascading catalytic ability as a novel oxidation therapeutic strategy for enhancing PDT.


Subject(s)
Breast Neoplasms/therapy , Keratins/pharmacokinetics , Nitric Oxide/pharmacology , Photochemotherapy/methods , Animals , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Female , Humans , Mice , Mice, Inbred BALB C , Nanoparticles/therapeutic use
3.
Bioorg Chem ; 107: 104607, 2021 02.
Article in English | MEDLINE | ID: mdl-33450543

ABSTRACT

An efficient and green method, combining enzymatic and visible-light catalysis for synthesis of the widely applicable 2-substituted benzothiazoles, has been developed. This method features a relay catalysis protocol consisting of biocatalytic promiscuity and visible-light-induced subsequent oxidization of 2-phenyl benzothiazolines. The whole reaction process is very high-efficiency, achieving 99% yield in just 10 min, under an air atmosphere, nearly 100% atomic utilization, and the 2-substituted benzothiazole products were obtained in good to excellent yields with a wide range of substrates. This reaction is the other example of combining the non-natural catalytic activity of hydrolases with visible-light catalysis for organic synthesis and the catalytic system does not require additional oxidants or metals, which is good for the environment.


Subject(s)
Benzothiazoles/chemical synthesis , Hydrolases/metabolism , Light , Benzothiazoles/chemistry , Benzothiazoles/metabolism , Catalysis , Oxidation-Reduction , Photosensitizing Agents/chemistry , Solvents/chemistry , Substrate Specificity
4.
Bioorg Chem ; 107: 104534, 2021 02.
Article in English | MEDLINE | ID: mdl-33339664

ABSTRACT

A novel strategy combining visible-light and enzyme catalysis in one pot for the synthesis of 4H-pyrimido[2,1-b] benzothiazole derivatives from alcohols is described for the first time. Fourteen 4H-pyrimido[2,1-b] benzothiazole derivatives were prepared with yields of up to 98% under mild reaction conditions by a simple operation. The photoorgano catalyst rose Bengal (rB) was employed to oxyfunctionalise alcohols to aldehydes. Compared with aldehydes, alcohols with more stable properties and lower cost, thus we used photocatalysis to oxidize alcohols into aldehydes. Next, the enzyme was used to further catalyze the reaction of Biginelli to produce the target product of 4H-pyrimidine [2,1-b] benzothiazole. Experimental results show that this method provides a more efficient and eco-friendly strategy for the synthesis of 4H-pyrimido[2,1-b] benzothiazole derivatives.


Subject(s)
Benzothiazoles/chemistry , Enzymes/metabolism , Light , Benzothiazoles/chemical synthesis , Benzothiazoles/metabolism , Biocatalysis , Candida/enzymology , Catalysis , Enzymes/chemistry , Fungal Proteins/metabolism , Humans , Lipase/metabolism , Oxidation-Reduction
5.
ACS Appl Bio Mater ; 3(8): 5193-5201, 2020 Aug 17.
Article in English | MEDLINE | ID: mdl-35021694

ABSTRACT

A series of aggregation-induced emission (AIE) fluorescence probes, coined 4H-pyrimido[2,1-b]benzothiazole derivatives, has been synthesized by Biginelli reactions. Utilizing spectroscopic techniques, their photophysical properties have been comprehensively investigated in working environment both in vitro and in vivo. Density functional theory (DFT) calculations were performed to better understand the mechanism of these probes. The interactions between 4H-pyrimido[2,1-b]benzothiazoles with different substituents and bovine serum albumin (BSA) were analyzed using UV-vis and fluorescence spectroscopy, synchronous fluorescence, and docking analysis. Studies found that 4H-pyrimido[2,1-b]benzothiazole could bind to bovine serum albumin (BSA) through a hydrogen bond and hydrophobic interactions, resulting in enhancement of fluorescence emission of probes 1a-6f and fluorescence quenching of BSA. Combined with cell imaging experiments, these provide information on potential effects of benzothiazoles on disease treatment.

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