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1.
Talanta ; 278: 126394, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38924984

RESUMO

Enzyme-activatable drug delivery systems have been developed for cancer diagnosis and therapy. However, targeted intracellular drug delivery is a challenge for precisely tumor imaging and therapy due to the increased stability of copolymer nanoparticles (NPs) is accompanied by a notable decrease in enzyme degradation. Herein, disulfide bond was designed as an enzyme-activatable molecular switch of SS-P(G2)2/DOX NPs. The copolymer NPs consists of polyvinylpyrrolidone (PVP) with disulfide bonds in the center and enzyme-degradable peptide dendrites (Phe-Lys) to form dendritic-linear-dendritic triblock copolymers (TBCs). The amphiphilic TBCs could be split into two identical amphiphilic diblock copolymers (DBCs) by glutathione (GSH) in cancer cells specifically while maintaining the same hydrophilic-lipophilic equilibrium. This structural transformation significantly reduced the stability of copolymer NPs and enhanced sensitivity of DOX release by cathepsin B-activated. Subsequently, the released DOX acted as an indicator of fluorescence imaging and chemotherapy drug for cancer cells. The polymeric NPs achieved excellent drug-loaded stability and prolonged blood circulation in vivo, and realized fluorescence imaging and specific cancer cell killing capabilities by responding to the overexpression of GSH and cathepsin B in tumor cells. Furthermore, the copolymer NPs demonstrated excellent blood compatibility and biosafety. Therefore, a novel strategy based on one tumor marker acting as the switch for another tumor microenvironment responsive drug delivery system could be designed for tumor intracellular imaging and chemotherapy.


Assuntos
Dissulfetos , Doxorrubicina , Liberação Controlada de Fármacos , Imagem Óptica , Humanos , Doxorrubicina/química , Doxorrubicina/farmacologia , Dissulfetos/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Nanopartículas/química , Camundongos , Portadores de Fármacos/química , Glutationa/química , Glutationa/metabolismo , Polímeros/química , Linhagem Celular Tumoral , Camundongos Nus , Catepsina B/metabolismo
2.
RSC Adv ; 13(32): 22079-22087, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37483668

RESUMO

Stimuli-responsive linear-dendritic block copolymers (LDBCs) have attracted significant research attention as novel drug carriers. We report here three generations of new enzyme and pH dual responsive linear-dendritic block copolymers (LDBCs) with a phenylalanyl-lysine (Phe-Lys) dipeptide linking hydrophilic linear poly(N-vinylpyrrolidone) (PNVP) and a hydrophobic peripherally ketal-functionalized dendron derived from 2,2'-bis(hydroxymethyl)propionic acid (bis-MPA). The LDBCs are synthesized via a combination of interchange of xanthates/reversible addition-fragmentation chain transfer (MADIX/RAFT) polymerization of N-vinylpyrrolidone (NVP) and "chain-first" strategy. Their structures are confirmed by 1H NMR spectra. The gel permeation chromatograph (GPC) analysis revealed that the LDBCs have a narrow molecular weight distribution (PDI ≤ 1.25). The amphiphilic LDBCs can self-assemble into spherical nanomicelles in aqueous solution. The presence of enzyme or/and the change of pH cause disassembly of micelles to release encapsulated cargos. The release rates of the guest molecules are faster in buffer solution at pH 5.0 than those upon the addition of the activating enzyme and can be fine-tuned by changing the generation of bis-MPA dendrons. The combination of enzyme and pH dual stimuli results in significantly accelerated and more complete release of the loaded hydrophobic guests. The cell viability assay confirmed the favorable biocompatibility until the LDBC micelle concentration reached 800 µg mL-1. These results indicate that the LDBCs can be considered as a good candidate for targeting drug delivery.

3.
Polymers (Basel) ; 11(10)2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31597356

RESUMO

In this study, we present the synthesis, self-assembly, and enzyme responsive nature of a unique class of well-defined amphiphilic linear-dendritic block copolymers (PNVP-b-dendr(Phe-Lys)n, n = 1-3) based on linear poly(N-vinylpyrrolidone) (PNVP) and dendritic phenylalanyl-lysine (Phe-Lys) dipeptides. The copolymers were prepared via a combination ofreversible addition-fragmentation chain transfer (RAFT) /xanthates (MADIX) polymerization of N-vinylpyrrolidone and stepwise peptide chemistry. The results of fluorescence spectroscopy, 1H NMR analyses, transmission electron microscopy (TEM), and particle size analysis demonstrated that the copolymers self-assemble in aqueous solution into micellar nanocontainers that can disassemble and release encapsulated anticancer drug doxorubicin or hydrophobic dye Nile red by trigger of a serine protease trypsin under physiological conditions. The disassembly of the formed micelles and release rates of the drug or dye can be adjusted by changing the generation of dendrons in PNVP-b-dendr(Phe-Lys)n. Furthermore, the cytocompatibility of the copolymers have been confirmed using human lung epithelial cells (BEAS-2B) and human liver cancer cells (SMMC-7721). Due to the fact of their enzyme responsive properties and good biocompatibility, the copolymers may have potential applicability in smart controlled release systems capable of site-specific response.

4.
Arch Pharm Res ; 30(3): 267-9, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17424929

RESUMO

A new pyrone derivative, 7, 9-dihydroxy-10-methyl-2H, 4aH, 6H, 10bH-pyrano[5,6-c][2]ben-zopyran-2,6-dione (1), was isolated from a culture broth of a strain of the fungus Cephalosporium sp. AL031, together with three known compounds, 3-acetyl-7-hydroxy-5-methoxyl-3H-isobenzofuran-1-one (2), vermopyrone (3), and 5-methylmellein (4). Their structures were elucidated by spectroscopic analysis including MS and 2D-NMR. Compounds 2, 3, and 4 are reported for the first time from fermentation broth of this fungus through the present study.


Assuntos
Acremonium/metabolismo , Pironas/isolamento & purificação , Fermentação , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Pironas/química , Pironas/metabolismo
5.
Nat Prod Res ; 19(4): 425-8, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15938151

RESUMO

Two new dihydroisocoumarins, 3,4-dihydro-3-heptantrienyl-8-hydroxyl-6-hydroxymethyl-5-methylisocoumarin and 6-acetoxymethylene-3,4-dihydro-3-heptantrienyl-8-hydroxyl-5-methylisocoumarin were isolated from a culture broth of a strain of the fungus, Cephalosporium sp. AL031. Their structures were elucidated by interpretation of their spectroscopic data.


Assuntos
Acremonium/química , Cumarínicos/química , Isocumarinas , Estrutura Molecular
6.
Zhong Yao Cai ; 27(1): 20-2, 2004 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-15179784

RESUMO

Three phenolic acids were isolated from the culture broth of the fungus Cephalosporium sp. AL031 whose metabolites have been proven to possess antifungal and antibacterial activities. Their structures were elucidated as 2,4-dihydroxy-3,6-dimethyl-benzoic acid (1),3,6-dihydroxy-2,4-dimethylbenzoic acid(2) and 4-hydroxy-phenylacetic acid(3) by IR, EIMS, 1HNMR, 13CNMR, DEPT, HMQC and HMBC.


Assuntos
Acremonium/química , Hidroxibenzoatos/isolamento & purificação , Micélio/química , Hidroxibenzoatos/análise , Hidroxibenzoatos/química , Estrutura Molecular , Fenilacetatos/isolamento & purificação
7.
Zhong Yao Cai ; 26(1): 21-2, 2003 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-12858768

RESUMO

Three compounds were isolated from the mycelium of the fungus Cephalosporium sp. AL031 whose metabolites have been proven to possess antifungal and antibacterial activities. Based on the spectral data and elemental analysis, they were identified as 3-hydroxy-ergosta-7,22-dien-6-one(A), penicillic acid(B), 4-hydroxy-3,6-dimethyl-2-pyrone(C). All of these compounds were obtained from the culture medium of this fungus for the first time.


Assuntos
Acremonium/química , Ergosterol/isolamento & purificação , Ácido Penicílico/isolamento & purificação , Pironas/isolamento & purificação , Ergosterol/análogos & derivados , Ergosterol/química , Micélio/química , Ácido Penicílico/química , Pironas/química
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