This study aimed to assess the therapeutic potential of nisin,5-fluorouracil(5FU)and selenium encapsulated in folate-conjugated thiolated chitosan nanoparticles(N/5FU/Se@FTCsNPs),combined with a probiotic cocktail of ...This study aimed to assess the therapeutic potential of nisin,5-fluorouracil(5FU)and selenium encapsulated in folate-conjugated thiolated chitosan nanoparticles(N/5FU/Se@FTCsNPs),combined with a probiotic cocktail of Lactobacillus acidophilus and Bifidobacterium bifidum,against colorectal cancer(CRC).The nanoparticles(277 nm,+9.2 mV)exhibited high drug loading efficiencies(5FU:89.11%,nisin:70.68%)and pH-responsive release,with minimal drug release under gastric conditions and∼60.7%release at colonic pH,facilitating targeted delivery.The formulation remained stable for over 40 d at−20°C and 4°C,demonstrating excellent biocompatibility(<2%hemolysis)and exhibiting strong mucoadhesive and mucus-penetrating abilities.In vitro,N/5FU/Se@FTCsNPs selectively targeted CT26 colon cancer cells(IC5n:1.57μg/ml)with minimal effects on healthy cells,enhanced cellular uptake,and induced ROS-mediated apoptosis.In vivo,oral administration-especially with probiotics-significantly reduced tumor volume,improved survival rates and alleviated chemotherapy-related side effects such as diarrhea and weight loss.Biodistribution studies confirmed increased tumor targeting and decreased off-target exposure.Mechanistically,the treatment downregulated oncogenes and inflammatory markers(2-to 12.5-fold),includingβ-catenin,mTOR,COX-2 and VEGF-α,while upregulating tumor suppressors and protective genes(4 to 14.8 fold),such as PTEN,CASP9 and Mucin 2(P<0.0001).This indicates inhibition of proliferation,metastasis,inflammation,and angiogenesis,along with improved gut barrier function.Cytokine profiling and histological analysis further confirmed reduced systemic inflammation and maintained hematological safety.These findings highlight N/5FU/Se@FTCsNPs combined with probiotics as a promising,safe and effective oral therapy for CRC,leveraging microbiota modulation and targeted delivery.展开更多
Acne is a highly common skin condition,estimated to affect 9.4%of the global population at some point in their lives.Today,there is a growing demand for environmentally conscious products that treat skin diseases with...Acne is a highly common skin condition,estimated to affect 9.4%of the global population at some point in their lives.Today,there is a growing demand for environmentally conscious products that treat skin diseases without harming the environment,known as Clean Beauty.For this reason,the objective is to develop a delivery system based on bacterial cellulose loaded with natural actives nisin and mandelic acid for acne treatment.The system,using bacterial cellulose(BC)from Komagataebacter xylinus fermentation,was tested for antibacterial and antioxidant activity,active release,cytotoxicity,Sscanning Eelectron microscopy,and product stability.The results of this study are promising:the BC system exhibited potent antibacterial activity against both standard and skinisolated strains,along with high antioxidant activity.The controlled release of active ingredients,peaking at 300 min,and the stability of antibacterial and antioxidant properties over 180 days underscore the system's potential as a shelf-stable product.Additionally,the minimal cytotoxicity observed affirms the safety of the formulation.This innovative approach not only aligns with the principles of clean beauty by avoiding petroleumbased components but also provides a sustainable and effective solution for managing acne.The integration of natural actives within a biodegradable matrix positions this product as a frontrunner in the future of dermocosmetics,meeting consumer demands for products that are both skin-friendly and environmentally responsible.展开更多
基金supported by the Research Council of Tarbiat Modares University and the Iran National Science Foundation(INSF)(Grant Number:4043897).
文摘This study aimed to assess the therapeutic potential of nisin,5-fluorouracil(5FU)and selenium encapsulated in folate-conjugated thiolated chitosan nanoparticles(N/5FU/Se@FTCsNPs),combined with a probiotic cocktail of Lactobacillus acidophilus and Bifidobacterium bifidum,against colorectal cancer(CRC).The nanoparticles(277 nm,+9.2 mV)exhibited high drug loading efficiencies(5FU:89.11%,nisin:70.68%)and pH-responsive release,with minimal drug release under gastric conditions and∼60.7%release at colonic pH,facilitating targeted delivery.The formulation remained stable for over 40 d at−20°C and 4°C,demonstrating excellent biocompatibility(<2%hemolysis)and exhibiting strong mucoadhesive and mucus-penetrating abilities.In vitro,N/5FU/Se@FTCsNPs selectively targeted CT26 colon cancer cells(IC5n:1.57μg/ml)with minimal effects on healthy cells,enhanced cellular uptake,and induced ROS-mediated apoptosis.In vivo,oral administration-especially with probiotics-significantly reduced tumor volume,improved survival rates and alleviated chemotherapy-related side effects such as diarrhea and weight loss.Biodistribution studies confirmed increased tumor targeting and decreased off-target exposure.Mechanistically,the treatment downregulated oncogenes and inflammatory markers(2-to 12.5-fold),includingβ-catenin,mTOR,COX-2 and VEGF-α,while upregulating tumor suppressors and protective genes(4 to 14.8 fold),such as PTEN,CASP9 and Mucin 2(P<0.0001).This indicates inhibition of proliferation,metastasis,inflammation,and angiogenesis,along with improved gut barrier function.Cytokine profiling and histological analysis further confirmed reduced systemic inflammation and maintained hematological safety.These findings highlight N/5FU/Se@FTCsNPs combined with probiotics as a promising,safe and effective oral therapy for CRC,leveraging microbiota modulation and targeted delivery.
基金financial support provided by the Coordination for the Improvement of Higher Education Personnel(CAPES)the Sao Paulo Research Foundation(FAPESP)+1 种基金the National Council for Scientific and Technological Development(CNPq,grant number 305815/2023-7)the deeptech Bioloxcell.
文摘Acne is a highly common skin condition,estimated to affect 9.4%of the global population at some point in their lives.Today,there is a growing demand for environmentally conscious products that treat skin diseases without harming the environment,known as Clean Beauty.For this reason,the objective is to develop a delivery system based on bacterial cellulose loaded with natural actives nisin and mandelic acid for acne treatment.The system,using bacterial cellulose(BC)from Komagataebacter xylinus fermentation,was tested for antibacterial and antioxidant activity,active release,cytotoxicity,Sscanning Eelectron microscopy,and product stability.The results of this study are promising:the BC system exhibited potent antibacterial activity against both standard and skinisolated strains,along with high antioxidant activity.The controlled release of active ingredients,peaking at 300 min,and the stability of antibacterial and antioxidant properties over 180 days underscore the system's potential as a shelf-stable product.Additionally,the minimal cytotoxicity observed affirms the safety of the formulation.This innovative approach not only aligns with the principles of clean beauty by avoiding petroleumbased components but also provides a sustainable and effective solution for managing acne.The integration of natural actives within a biodegradable matrix positions this product as a frontrunner in the future of dermocosmetics,meeting consumer demands for products that are both skin-friendly and environmentally responsible.
