The therapeutic potential of curcumin(Cur) is hampered by its poor aqueous solubility and low bioavailability. The aim of this study was to determine whether Cur nanoemulsions enhance the efficacy of Cur against prost...The therapeutic potential of curcumin(Cur) is hampered by its poor aqueous solubility and low bioavailability. The aim of this study was to determine whether Cur nanoemulsions enhance the efficacy of Cur against prostate cancer cells and increase the oral absorption of Cur. Cur nanoemulsions were developed using the self-microemulsifying method and characterized by their morphology, droplet size and zeta potential. The results showed that the cytotoxicity and cell uptake were considerably increased with Cur nanoemulsions compared to free Cur. Cur nanoemulsions exhibited a significantly prolonged biological activity and demonstrated better therapeutic efficacy than free Cur, as assessed by apoptosis and cell cycle studies. In situ single-pass perfusion studies demonstrated higher effective permeability coefficient and absorption rate constant for Cur nanoemulsions than for free Cur. Our study suggested that Cur nanoemulsions can be used as an effective drug delivery system to enhance the anticancer effect and oral bioavailability of Cur.展开更多
Cancer immunotherapy is an effective antitumor approach through activating immune systems to eradicate tumors by immunotherapeutics.However,direct administration of“naked”immunotherapeutic agents(such as nucleic aci...Cancer immunotherapy is an effective antitumor approach through activating immune systems to eradicate tumors by immunotherapeutics.However,direct administration of“naked”immunotherapeutic agents(such as nucleic acids,cytokines,adjuvants or antigens without delivery vehicles)often results in:(1)an unsatisfactory efficacy due to suboptimal pharmacokinetics;(2)strong toxic and side effects due to low targeting(or off-target)efficiency.To overcome these shortcomings,a series of polysaccharide-based nanoparticles have been developed to carry immunotherapeutics to enhance antitumor immune responses with reduced toxicity and side effects.Polysaccharides are a family of natural polymers that hold unique physicochemical and biological properties,as they could interact with immune system to stimulate an enhanced immune response.Their structures offer versatility in synthesizing multifunctional nanocomposites,which could be chemically modified to achieve high stability and bioavailability for delivering therapeutics into tumor tissues.This review aims to highlight recent advances in polysaccharide-based nanomedicines for cancer immunotherapy and propose new perspectives on the use of polysaccharide-based immunotherapeutics.展开更多
Telomerase plays an essential role in many biological processes.DNA methylation regulates the expression of many genes,including telomerase.Here,we propose a deformable satellite nanocapsule fluorescein isothiocyanate...Telomerase plays an essential role in many biological processes.DNA methylation regulates the expression of many genes,including telomerase.Here,we propose a deformable satellite nanocapsule fluorescein isothiocyanate(FITC)-hollowbowl mesoporous organicsilica@gold nanoparticles-methyl-CpG-binding protein 2(MECP 2)-silver nanoclusters(FHBMO@AMA),for simultaneous quantitative detection of both cytoplasmic telomerase activity and the degree of DNA methylation.This strategy enabled spatial-based detection in cells.The total cytoplasmic telomerase activity was detected by fluorescence energy resonance transfer(FRET)between FHBMO and gold nanoparticles(Au NPs),while the DNA methylation in the nucleus was detected by enhanced fluorescence of silver nanoclusters(Ag NCs).Furthermore,FHBMO@AMA could intuitively distinguish between the differences in telomerase expression in cells during the DNA synthesis period at the mitotic phase(S/M)of the cell cycle.Interestingly,the ratio of the two detections(telomerase activity/DNA methylation)significantly correlated with the efficacy of anticancer drugs.At the same time,there was no apparent linear relationship between any single detection target and the efficacy of the anticancer drugs.Therefore,based on the relationship between telomerase activity and DNA methylation,our newly developed approach serves as new and feasible method for evaluating the efficacy of anticancer drugs,thereby,extending the technology toolbox for precision in medical and pharmaceutical analysis of drug potency.展开更多
基金supported by grants from the Doctoral Program Foundation of Henan University of Traditional Chinese Medicine(No.BSJJ2011-04)Specialized Research Fund of Henan University of Traditional Chinese Medicine(No.2014KYYWF-QN12)
文摘The therapeutic potential of curcumin(Cur) is hampered by its poor aqueous solubility and low bioavailability. The aim of this study was to determine whether Cur nanoemulsions enhance the efficacy of Cur against prostate cancer cells and increase the oral absorption of Cur. Cur nanoemulsions were developed using the self-microemulsifying method and characterized by their morphology, droplet size and zeta potential. The results showed that the cytotoxicity and cell uptake were considerably increased with Cur nanoemulsions compared to free Cur. Cur nanoemulsions exhibited a significantly prolonged biological activity and demonstrated better therapeutic efficacy than free Cur, as assessed by apoptosis and cell cycle studies. In situ single-pass perfusion studies demonstrated higher effective permeability coefficient and absorption rate constant for Cur nanoemulsions than for free Cur. Our study suggested that Cur nanoemulsions can be used as an effective drug delivery system to enhance the anticancer effect and oral bioavailability of Cur.
基金This work was supported by the National Natural Science Foundation of China(51873120,51673127,81621003)National Science and Technology Major Project of China(2017ZX09304023)+1 种基金Ruilong Sheng,Helena Tomas and Joao Rodrigues appreciate the support from Fundaçao para a Ciencia e a Tecnologia(Base Fund UIDB/00674/2020,CQM,Portuguese Government Funds)ARDITI-Agencia Regional para o Desenvolvimento da Investigaçao Tecnologia e Inovaçao through the project M1420-01-0145-FEDER-000005-Centro de Química da Madeira-CQM+(Madeira 14-20 Program)and ARDITI-2017-ISG-003.
文摘Cancer immunotherapy is an effective antitumor approach through activating immune systems to eradicate tumors by immunotherapeutics.However,direct administration of“naked”immunotherapeutic agents(such as nucleic acids,cytokines,adjuvants or antigens without delivery vehicles)often results in:(1)an unsatisfactory efficacy due to suboptimal pharmacokinetics;(2)strong toxic and side effects due to low targeting(or off-target)efficiency.To overcome these shortcomings,a series of polysaccharide-based nanoparticles have been developed to carry immunotherapeutics to enhance antitumor immune responses with reduced toxicity and side effects.Polysaccharides are a family of natural polymers that hold unique physicochemical and biological properties,as they could interact with immune system to stimulate an enhanced immune response.Their structures offer versatility in synthesizing multifunctional nanocomposites,which could be chemically modified to achieve high stability and bioavailability for delivering therapeutics into tumor tissues.This review aims to highlight recent advances in polysaccharide-based nanomedicines for cancer immunotherapy and propose new perspectives on the use of polysaccharide-based immunotherapeutics.
基金The authors gratefully acknowledge the financial support from the National Natural Science Foundation of China(nos.21834004 and 21904063)the Natural Science Foundation of Jiangsu Province(no.BK20190279).
文摘Telomerase plays an essential role in many biological processes.DNA methylation regulates the expression of many genes,including telomerase.Here,we propose a deformable satellite nanocapsule fluorescein isothiocyanate(FITC)-hollowbowl mesoporous organicsilica@gold nanoparticles-methyl-CpG-binding protein 2(MECP 2)-silver nanoclusters(FHBMO@AMA),for simultaneous quantitative detection of both cytoplasmic telomerase activity and the degree of DNA methylation.This strategy enabled spatial-based detection in cells.The total cytoplasmic telomerase activity was detected by fluorescence energy resonance transfer(FRET)between FHBMO and gold nanoparticles(Au NPs),while the DNA methylation in the nucleus was detected by enhanced fluorescence of silver nanoclusters(Ag NCs).Furthermore,FHBMO@AMA could intuitively distinguish between the differences in telomerase expression in cells during the DNA synthesis period at the mitotic phase(S/M)of the cell cycle.Interestingly,the ratio of the two detections(telomerase activity/DNA methylation)significantly correlated with the efficacy of anticancer drugs.At the same time,there was no apparent linear relationship between any single detection target and the efficacy of the anticancer drugs.Therefore,based on the relationship between telomerase activity and DNA methylation,our newly developed approach serves as new and feasible method for evaluating the efficacy of anticancer drugs,thereby,extending the technology toolbox for precision in medical and pharmaceutical analysis of drug potency.