RESUMO
Doxorubicin (DOX) is one of the most commonly used anticancer drugs; however, its clinical application is greatly limited due to its toxicity and chemotherapy resistance. The delivery of DOX by liposomes (Lipos) can improve the blood circulation time in vivo and reduce toxic side effects, but the drug's accumulation in the tumor is often insufficient for effective treatment. In this study, we present a calcium cross-linked liposome gel for the encapsulation of DOX, demonstrating its superior long-term release capabilities compared to conventional Lipos. By leveraging this enhanced long-term release, we can enhance drug accumulation within tumors, ultimately leading to improved antitumor efficacy. Lipos were prepared using the thin-film dispersion method in this study. We utilized the ion-responsiveness of glutathione-gelatin (GSH-GG) to form the gel outside the Lipos and named the nanoparticles coated with GSH-GG on the outside of Lipos as Lipos@GSH-GG. The average size of Lipos@GSH-GG was around 342.9 nm, with a negative charge of -25.6 mV. The in vitro experiments revealed that Lipos@GSH-GG exhibited excellent biocompatibility and slower drug release compared to conventional Lipos. Further analysis of cellular uptake and cytotoxicity demonstrated that Lipos@GSH-GG loading DOX (DOX&Lipos@GSH-GG) exhibited superior long-term release effects and lower toxic side effects compared to Lipos loading DOX (DOX&Lipos). Additionally, the findings regarding the long-term release effect in vivo and the tumor accumulation within tumor-bearing mice of Lipos@GSH-GG suggested that, compared to Lipos, it demonstrated superior long-term release capabilities and achieved greater drug accumulation within tumors. In vivo antitumor efficacy experiments showed that DOX&Lipos@GSH-GG demonstrated superior antitumor efficacy to DOX&Lipos. Our study highlights Lipos@GSH-GG as a promising nanocarrier with the potential to enhance efficacy and safety by means of long-term release effects and may offer an alternative approach for effective antitumor therapy in the future.
Assuntos
Cálcio , Doxorrubicina , Liberação Controlada de Fármacos , Glutationa , Lipossomos , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Animais , Camundongos , Lipossomos/química , Humanos , Cálcio/química , Cálcio/metabolismo , Glutationa/química , Feminino , Géis/química , Gelatina/química , Camundongos Nus , Nanopartículas/química , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Reagentes de Ligações Cruzadas/química , Sistemas de Liberação de Medicamentos/métodosRESUMO
Excessive reactive oxygen species (ROS) can lead to the imbalance of antioxidant system in the body and cause oxidative damage to cells. It is imperative to rationally design nanomaterials with high catalytic activity and multiple antioxidant activities. Here, line peppers-derived carbon dots (CDs) is encapsulated into zeolitic imidazolate framework-8 (CDs@ZIF-8) to achieve enhanced antioxidant activities for improved protective effect on cells. This nanosystem has a broad spectrum of antioxidant properties, which can effectively remove a variety of intracellular ROS and protect cells from ROS-induced death and cytoskeleton damage. In addition, CDs@ZIF-8 can reduce malondialdehyde (MDA) level and increase the enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), as well as the level of glutathione (GSH) in human kidney proximal tubular epithelial cells (HK-2) cells. Mechanism studies demonstrated that CDs@ZIF-8 can up-regulate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), allowing the regulation of antioxidant enzymes to further achieve antioxidant effect. Besides, CDs@ZIF-8 inhibited the secretion of proinflammatory cytokines. This work demonstrates that the constructed CDs@ZIF-8 with multi-antioxidant activity can act as a highly efficient intracellular ROS scavenger and provide potential for the application in related oxidative stress-induced diseases.
RESUMO
Bacterial infections are a significant global health concern, particularly in the context of skin infections and chronic wounds, which was further exacerbated by the emerging of antibiotic resistance. Therefore, there are urgent needs to develop alternative antibacterial strategies without inducing significant resistance. Photothermal therapy (PTT) is a promising alternative approach but usually faces limitations such as the need for stable and environmental-friendly PTT agents and ensuring biocompatibility with living tissues, necessitating ongoing research for its clinical advancement. Herein, in this study, with the aim to develop a green synthesized PTT agent for photothermal enhanced antibacterial and wound healing, we proposed a facile one-pot method to prepare epigallocatechin gallate-ferric (EGCG-Fe) complex nanoparticles. The obtained nanoparticles showed improved good size distribution and stability with high reproducibility. More importantly, EGCG-Fe complex nanoparticles have additional photothermal conversion ability which can give photothermal enhanced antibacterial effect on various pathogens, including Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) strains. EGCG-Fe complex nanoparticles also showed powerful biofilm prevention and destruction effects with promoted antibacterial and wound healing on mice model. In conclusion, EGCG-Fe complex nanoparticles can be a robust green material with effective and novel light controllable antibacterial properties for photothermal enhanced antibacterial and wound healing applications.