Galactosed and Reduction-Responsive Nanoparticles Assembled from Trimethylchitosan–Camptothecin Conjugates for Enhanced Hepatocellular Carcinoma Therapy

Fu, Chen; Qin, Jing-can; Fan, Haosen; Kong, Fei

doi:10.3390/pharmaceutics14071315

Cited by 8 publications

(4 citation statements)

References 38 publications

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“…N,N,N-trimethyl chitosan (TMC) is a chitosan derivative containing permanent positive charges of quaternary salts on C2 of the main backbone. This chemical modi cation enhances the biological properties such as antimicrobial, anticoagulant, antioxidant and mucoadhesive, making TMC an attractive biopolymer for tissue engineering, wound dressings and hygiene related textiles [13,19,[56][57][58][59][60][61].…”

Section: Discussionmentioning

confidence: 99%

Biodegradable trimethyl chitosan nanofiber mats as bioabsorbable dressings for wound closure and healing

Anisiei

Andreica

Mititelu-Tarțău

et al. 2023

Preprint

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Background Quaternary chitosan based fibers have emerged as promising biomaterials for tissue engineering, wound healing and hygiene related textiles, but their in vivo application is restricted by the lack of biodegradability of the synthetic polymers used as co-spinning agents. Herein, we report fully biodegradable chitosan/N,N,N-trimethyl chitosan (TMC) nanofibers prepared via electrospinning, when using poly(ethylene glycol) as sacrificial additive, as potential bioabsorbable wound dressings.Methods The composition and morphology of the fiber mats was confirmed by Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance, thermogravimetric analysis, wide angle X-ray diffraction, polarized optical microscopy and scanning electron microscopy. Their properties required for in vivo application, such as behavior in moisture media (dynamic vapor sorption, swelling and enzymatic degradation tests), muco- and bio-adhesive character, mechanical properties and antimicrobial activity were measured. The in vitro biocompatibility on normal human dermal fibroblasts was investigated in line with standards for biomedical devices and in vivo acute toxicity and biocompatibility was assessed by monitoring hematological, biochemical and immunological profile on Wistar rats. Wound closure and healing was studied on burn wound healing models in rats.Results The combination of chitosan with its TMC derivative into nanofibers enabled high swelling ability and fluid exchange, biodegradability rate controlled by the TMC content and pH of media, muco- and bio-adhesive character, mechanical properties similar to skin tissue, strong antimicrobial activity against relevant pathogens and in vitro and in vivo biocompatibility. Moreover, their subcutaneous implantation in rats revealed in vivo biodegradation and lack of toxicity. As a proof of concept, the fiber mats application on burn wound healing models in rats showed wound closure and active healing, with fully restoration of epithelia.Conclusions The use of poly(ethylene glycol) with double role, electrospinning and sacrificial additive, is a straight pathway to the obtaining of chitosan/TMC nanofibers. The combination of chitosan with its N,N,N-trimethyl chitosan derivative into nanofiber mats provide a bioabsorbable bandage which favors rapid wound closure and fully restoration of the skin tissue.

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Section: Discussionmentioning

confidence: 99%

Biodegradable trimethyl chitosan nanofiber mats as bioabsorbable dressings for wound closure and healing

Anisiei

Andreica

Mititelu-Tarțău

et al. 2023

Preprint

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“…Notwithstanding, its broader therapeutic application is hindered by several poor clinical outcomes ascribed to this drug such as low bioavailability and systemic toxicity. In this regard, various modifications of CPT have been reported in the last years. − A wide range of chemical moieties have been conjugated at the hydroxy group in the α position of the lactone functional group to improve its antitumoral effects. − Interestingly, two Se prodrugs ( 27 and 28 ) (Figure ) have been synthesized by the introduction of a diselenide moiety in this drug structure and have exhibited significantly higher cytotoxic effects to different cancer cell lines compared to CPT (Table ). Furthermore, these CPT analogues unveiled efficient in vivo antitumoral activities and good tolerance in a mouse model compared to the parent drug …”

Section: Selenized Small Molecule Drugsmentioning

confidence: 99%

Selenization of Small Molecule Drugs: A New Player on the Board

Morán-Serradilla,

Plano,

Sanmartín

et al. 2024

J. Med. Chem.

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There is an urgent need to develop safer and more effective modalities for the treatment of a wide range of pathologies due to the increasing rates of drug resistance, undesired side effects, poor clinical outcomes, etc. Throughout the years, selenium (Se) has attracted a great deal of attention due to its important role in human health. Besides, a growing body of work has unveiled that the inclusion of Se motifs into a great number of molecules is a promising strategy for obtaining novel therapeutic agents. In the current Perspective, we have gathered the most recent literature related to the incorporation of different Se moieties into the scaffolds of a wide range of known drugs and their feasible pharmaceutical applications. In addition, we highlight different representative examples as well as provide our perspective on Se drugs and the possible future directions, promises, opportunities, and challenges of this ground-breaking area of research. ■ SIGNIFICANCE • Significance: The development of novel compounds for the treatment of numerous pathologies has become a priority due to the lack of effective therapeutic options. • Impact: This work highlights the potential of incorporating Se moieties into the scaffold of several drugs to develop novel safer bioactive compounds. • Innovation: This Perspective discusses the development of selenoderivatives of a wide array of drugs and their biological applications and proposes novel avenues to continue exploring this outstanding research area.

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“…Hemoglobin-curcumin nanostructures have been shown to be advantageous in reducing invasion of HCC cells, suppressing vascular mimics and enhancing radio-sensitivity in hypoxic tumor microenvironment via inhibiting growth and DNA damage repair [92] . Trimetylchitosan-camptothecin conjugates can be considered as reduction-sensitive nanostructures in HCC suppression, providing targeted delivery of drug, reducing premature release and inhibiting tumor growth in vitro and in vivo [93] . Hence, nanostructures are promising candidates for sustained delivery of drugs in HCC therapy [94] .…”

Section: Hepatocellular Carcinoma: An Overviewmentioning

confidence: 99%

Multifunctional and stimuli-responsive liposomes in hepatocellular carcinoma diagnosis and therapy

Samaei,

Daryab,

Gholami

et al. 2024

Translational Oncology

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Galactosed and Reduction-Responsive Nanoparticles Assembled from Trimethylchitosan–Camptothecin Conjugates for Enhanced Hepatocellular Carcinoma Therapy

Cited by 8 publications

References 38 publications

Biodegradable trimethyl chitosan nanofiber mats as bioabsorbable dressings for wound closure and healing

Biodegradable trimethyl chitosan nanofiber mats as bioabsorbable dressings for wound closure and healing

Selenization of Small Molecule Drugs: A New Player on the Board

Multifunctional and stimuli-responsive liposomes in hepatocellular carcinoma diagnosis and therapy

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