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1.
J Trace Elem Med Biol ; 83: 127389, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38242004

RESUMO

BACKGROUND: Minerals are important not only for better plant growth and development but also for human and animal nutrition. It is known that east and west Gojam in the Amhara region and east and west Shoa areas in the Oromia region Ethiopia's most teff growing areas. However, there is no information on the mineral content and nutritional worth of Teff Sire district, Arsi zone, Ethiopia. Since ICP OES is a powerful technique to examine elemental compositions even in lower concentration, it is used in this work to investigate the elemental composition of red teff samples. METHODS: The elemental compositions of red Teff grain samples were determined using ICP-OES from three sites: S1, S2, and S3 of Sire district, Arsi zone, Ethiopia. Wet digestion of the teff samples was carried out by weighing 0.5 g red teff sample and digested with 8 ml HNO3 and 2 ml H2O2 (30%) for 3:00 h at a temperature of 100℃ on hot plate. The investigations of method validation, limit of detection and limit of quantification were also carried out. RESULTS: The average amount of elements in red teff sample obtained as 172-280 mg/kg Fe, 13-76 mg/kg Mn, 8.2-8.5 mg/kg Cu, 24-26 mg/kg Zn, and toxic trace elements 0.12-0.29 mg/kg Pb and 0.15-0.22 mg/kg Cd. The limit of detection found in ranges from 0.21 mg Kg-1 to 10.44 mg Kg-1 whereas quantification limit resulted in 0.7 mg Kg-1 to 34.8 mg Kg-1 for the metals under consideration. The method was validated by its linear range in the concentration range of 0.028-1.4 ppm or 0.056-2.8 ppm and excellent recovery result was achieved in the range of 90-120%. CONCLUSION: This study aimed to investigate the mineral content in red teff cultivated in Ethiopia specifically Arsi zone by using ICP OES. From the obtained results, Iron was the first abundant essential element in red teff compared to Mn, Cu and Zn. The level of trace elements: Cd and Pb in the samples slightly above the acceptable limit, possibly due to agricultural practices like usage of fertilizers, pesticides, and other industrial products. Overall, this red teff elemental composition information contributes to the nutrition database and food safety in Ethiopia and beyond.


Assuntos
Eragrostis , Oligoelementos , Humanos , Animais , Oligoelementos/análise , Etiópia , Cádmio , Peróxido de Hidrogênio , Chumbo , Análise Espectral , Minerais
2.
Pharmaceutics ; 12(11)2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33182410

RESUMO

Maximizing the antitumor efficacy of doxorubicin (DOX) with a new drug delivery strategy is always desired in the field of biomedical science. Because the clinical applications of DOX in the treatment of cancer is limited by the side effects related to the dose. Herein, we report the co-loading of DOX and resveratrol (RESV) using an injectable in situ formed sodium deoxycholate hydrogel (Na-DOC-hyd) at the pH of the tumor extracellular microenvironment. The sequential, controlled, and sustained release of RESV and DOX for synergistic antitumor effects was confirmed by entrapping G4.5-DOX in the RESV-loaded Na-DOC hydrogel (Na-DOC-hyd-RESV). The synergistic antitumor activity of Na-DOC-hyd-RESV+G4.5-DOX was assessed on HeLa cell xenograft tumor in BALB/c nude mice. In the MTT biocompatibility assay, both the G4.5 PAMAM dendrimer and Na-DOC-hyd exhibited negligible cytotoxicity up to the highest dose of 2.0 mg mL-1 in HeLa, MDA-MB-231, and HaCaT cells. The release profiles of DOX and RESV from the Na-DOC-hyd-RESV+G4.5-DOX confirmed the relatively rapid release of RESV (70.43 ± 1.39%), followed by that of DOX (54.58 ± 0.62%) at pH 6.5 in the 7 days of drug release studies. A single intratumoral injection of Na-DOC-hyd-RESV+G4.5-DOX maximally suppressed tumor growth during the 28 days of the treatment period. Na-DOC-hyd-RESV+G4.5-DOX did not cause any histological damage in the major visceral organs. Therefore, this Na-DOC-hydrogel for dual drugs (DOX and RESV) delivery at the pH of the tumor extracellular microenvironment is a promising, safe, and effective combination for antitumor chemotherapy.

3.
Polymers (Basel) ; 12(11)2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33172099

RESUMO

Hydrogels have been investigated as ideal biomaterials for wound treatment owing to their ability to form a highly moist environment which accelerates cell migration and tissue regeneration for prompt wound healing. They can also be used as a drug carrier for local delivery, and are able to activate immune cells to enhance wound healing. Here, we developed heparin-conjugated poly(N-isopropylacrylamide), an injectable, in situ gel-forming polymer, and evaluated its use in wound healing. Ibuprofen was encapsulated into the hydrogel to help reduce pain and excessive inflammation during healing. In addition to in vitro studies, a BALB/c mice model was used to evaluate its effect on would healing and the secretion of inflammatory mediators. The in vitro assay confirmed that the ibuprofen released from the hydrogel dramatically reduced lipopolysaccharide-induced inflammation by suppressing the production of NO, PGE2 and TNF-α in RAW264.7 macrophages. Moreover, an in vivo wound healing assay was conducted by applying hydrogels to wounds on the backs of mice. The results showed that the ibuprofen-loaded hydrogel improved healing relative to the phosphate buffered saline group. This study indicates that ibuprofen loaded in an injectable hydrogel is a promising candidate for wound healing therapy.

4.
Pharmaceutics ; 12(6)2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32585885

RESUMO

Polymeric micelles (PMs) have been used to improve the poor aqueous solubility, slow absorption and non-selective biodistribution of chemotherapeutic agents (CAs), albeit, they suffer from disassembly and premature release of payloads in the bloodstream. To alleviate the thermodynamic instability of PMs, different core crosslinking approaches were employed. Herein, we synthesized the poly(ethylene oxide)-b-poly((2-aminoethyl)diselanyl)ethyl l-aspartamide)-b-polycaprolactone (mPEG-P(LA-DSeDEA)-PCL) copolymer which self-assembled into monodispersed nanoscale, 156.57 ± 4.42 nm, core crosslinked micelles (CCMs) through visible light-induced diselenide metathesis reaction between the pendant selenocystamine moieties. The CCMs demonstrated desirable doxorubicin (DOX)-loading content (7.31%) and encapsulation efficiency (42.73%). Both blank and DOX-loaded CCMs (DOX@CCMs) established appreciable colloidal stability in the presence of bovine serum albumin (BSA). The DOX@CCMs showed redox-responsive drug releasing behavior when treated with 5 and 10 mM reduced glutathione (GSH) and 0.1% H2O2. Unlike the DOX-loaded non-crosslinked micelles (DOX@NCMs) which exhibited initial burst release, DOX@CCMs demonstrated a sustained release profile in vitro where 71.7% of the encapsulated DOX was released within 72 h. In addition, the in vitro fluorescent microscope images and flow cytometry analysis confirmed the efficient cellular internalization of DOX@CCMs. The in vitro cytotoxicity test on HaCaT, MDCK, and HeLa cell lines reiterated the cytocompatibility (≥82% cell viability) of the mPEG-P(LA-DSeDEA)-PCL copolymer and DOX@CCMs selectively inhibit the viabilities of 48.85% of HeLa cells as compared to 15.75% of HaCaT and 7.85% of MDCK cells at a maximum dose of 10 µg/mL. Overall, all these appealing attributes make CCMs desirable as nanocarriers for the delivery and controlled release of DOX in tumor cells.

5.
Pharmaceutics ; 12(5)2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32403321

RESUMO

Biotin receptors are overexpressed by various types of solid cancer cells and play a significant role in tumor metabolism, growth, and metastasis. Thus, targeting the biotin receptors on tumor cells may enhance the efficiency and reduce the side-effects of chemotherapy. The aim of this study was to develop a biotin-coupled poly(amido)amine (PAMAM) (PG4.5) dendrimer nanoparticle to enhance the tumor-specific delivery and intracellular uptake of anticancer drugs via receptor-mediated endocytosis. We modified PG4.5 with diethylenetriamine (DETA) followed by biotin via an amide bond and characterized the resulting PG4.5-DETA-biotin nanoparticles by 1H NMR, FTIR, and Raman spectroscopy. Loading and releasing of gemcitabine (GEM) from PG4.5-DETA-biotin were evaluated by UV-Visible spectrophotometry. Cell viability and cellular uptake were examined by MTT assay and flow cytometry to assess the biocompatibility, cellular internalization efficiency and antiproliferative activity of PG4.5-DETA-biotin/GEM. Gemcitabine-loaded PG4.5-DETA-biotin nanoparticles were spherical with a particle size of 81.6 ± 6.08 nm and zeta potential of 0.47 ± 1.25 mV. Maximum drug-loading content and encapsulation efficiency were 10.84 ± 0.16% and 47.01 ± 0.71%, respectively. Nearly 60.54 ± 1.99% and 73.96 ± 1.14% of gemcitabine was released from PG4.5-DETA-biotin/GEM nanoparticles after 48 h at the acidic pH values of 6.5 and 5, respectively. Flow cytometry and fluorescence microscopy of cellular uptake results revealed PG4.5-DETA-biotin/GEM nanoparticles selectively targeted cancer cells in vitro. Cytotoxicity assays demonstrated gemcitabine-loaded PG4.5-DETA-biotin significantly reduced cell viability and induced apoptosis in HeLa cells. Thus, biotin-coupled PG4.5-DETA nanocarrier could provide an effective, targeted drug delivery system and selectively convey gemcitabine into tumor cells.

6.
Mater Sci Eng C Mater Biol Appl ; 106: 110245, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31753357

RESUMO

The recent discovery of small interfering RNAs (siRNAs) has opened new avenues for designing personalized treatment options for various diseases. However, the therapeutic application of siRNAs has been confronted with many challenges because of short half-life in circulation, poor membrane penetration, difficulty in escaping from endosomes, and insufficient release into the cytosol. To overcome these challenges, we designed a diethylenetriamine (DETA)- and tetraethylenepentamine (TEPA)-modified polyamidoamine dendrimer generation 4.5 (PDG4.5), and characterized it using 1H nuclear magnetic resonance (NMR), 13C NMR, correlation spectroscopy (COSY), heteronuclear single-quantum correlation spectroscopy (HSQC), and Fourier transform infrared (FTIR) spectroscopy followed by conjugation with siRNA. The PDG4.5-DETA and PDG4.5-TEPA polyplexes exhibited spherical nanosize, ideal zeta potential, and effective siRNA binding ability, protected the siRNA from nuclease attack, and revealed less cytotoxicity of PDG4.5-DETA and PDG4.5-TEPA in HeLa cells. More importantly, the polyplexes also revealed good cellular internalization and facilitated translocation of the siRNA into the cytosol. Thus, PDG4.5-DETA and PDG4.5-TEPA can act as potential siRNA carriers in future medical and pharmaceutical applications.


Assuntos
Dendrímeros/química , Etilenodiaminas/química , Nylons/química , Poliaminas/química , RNA Interferente Pequeno/química , Portadores de Fármacos/química , Células HeLa , Humanos , Espectroscopia de Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier
7.
Int J Pharm ; 572: 118799, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31678386

RESUMO

In a malignant tumor, overexpression of pro-angiogenic factors like vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks characterized by leaky, chaotically organized, immature, thin-walled, and ill-perfused. As a result, hostile tumor environment would be developed and profoundly hinders anti-cancer drug activities and fuels tumor progression. In this study, we develop a strategy of sequential sustain release of anti-angiogenic drug, Bevacizumab (BVZ), and anti-cancer drug, Doxorubicin (DOX), using poly (d, l-Lactide)- Poly (ethylene glycol) -Poly (d, l-Lactide) (PDLLA-PEG-PDLLA) hydrogel as a local delivery system. The release profiles of the drugs from the hydrogel were investigated in vitro which confirmed that relatively rapid release of BVZ (73.56 ±â€¯1.39%) followed by Dox (61.21 ±â€¯0.62%) at pH 6.5 for prolonged period. The in vitro cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. Likeways, the in vitro degradation of the copolymer showed 41.63 ±â€¯2.62% and 73.25 ±â€¯4.36% weight loss within 6 weeks at pH 7.4 and 6.5, respectively. After a single intratumoral injection of the drug-encapsulated hydrogel on Hela xenograft nude, hydrogel co-loaded with BVZ and Dox displayed the highest tumor suppression efficacy for up to 36 days with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drug by hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Antibióticos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Doxorrubicina/administração & dosagem , Neovascularização Patológica , Poliésteres/química , Polietilenoglicóis/química , Polímeros Responsivos a Estímulos/química , Temperatura , Neoplasias do Colo do Útero/irrigação sanguínea , Neoplasias do Colo do Útero/tratamento farmacológico , Inibidores da Angiogênese/química , Animais , Antibióticos Antineoplásicos/química , Protocolos de Quimioterapia Combinada Antineoplásica/química , Bevacizumab/química , Preparações de Ação Retardada , Doxorrubicina/química , Portadores de Fármacos , Composição de Medicamentos , Liberação Controlada de Fármacos , Feminino , Células HeLa , Humanos , Hidrogéis , Concentração de Íons de Hidrogênio , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Colloids Surf B Biointerfaces ; 184: 110531, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590053

RESUMO

Iron oxide-based magnetic resonance imaging (MRI) contrast agents have negative contrast limitations in cancer diagnosis. Gadolinium (Gd)-based contrast agents show toxicity. To overcome these limitations, Gd-doped ferrite (Gd:Fe3O4 (GdIO) nanoparticles (NPs) were synthesized as T1-T2 dual-modal contrast agents for MRI-traced drug delivery. A theranostics GdIO encapsulated in a Generation 4.5 PAMAM dendrimer (G4.5-GdIO) was developed by alkaline coprecipitation. The drug-loading efficiency of the NPs was ∼24%. In the presence of a low-frequency alternating magnetic field (LFAMF), a maximum cumulative doxorubicin (DOX) release of ∼77.47% was achieved in a mildly acidic (pH = 5.0) simulated endosomal microenvironment. Relaxometric measurements indicated superior r1 (5.19 mM-1s-1) and r2 (26.13 mM-1s-1) for G4.5-GdIO relative to commercially available Gd-DTPA. Thus, G4.5-GdIO is promising as an alternative noninvasive MRI-traced cancer drug delivery system.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Dendrímeros/química , Doxorrubicina/farmacologia , Nanopartículas/química , Poliaminas/química , Nanomedicina Teranóstica , Antibióticos Antineoplásicos/química , Cápsulas/síntese química , Cápsulas/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste/síntese química , Meios de Contraste/química , Dendrímeros/síntese química , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Férricos/química , Gadolínio/química , Células HeLa , Humanos , Imageamento por Ressonância Magnética , Tamanho da Partícula , Poliaminas/síntese química , Propriedades de Superfície
9.
Mater Sci Eng C Mater Biol Appl ; 103: 109803, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349440

RESUMO

Redox-responsive diselenide bond containing triblock copolymer Bi(mPEG-SeSe)-PCL,Bi(mPEG-SeSe)-PCL was developed for specific drug release in cancer cells. Initially, ditosylated polycaprolactone was prepared via the reaction between polycaprolactone diol (PCL-diol) and tosyl chloride (TsCl). Next, Bi(mPEG-SeSe)-PCL was synthesized via the reaction between ditosylated polycaprolactone and sodium diselenide initiated poly (ethylene glycol) methyl ether tosylate. The synthesized amphiphilic triblock copolymer could self-assemble into uniform nanoparticles in aqueous medium and disassemble upon redox stimuli. The Bi(mPEG-SeSe)-PCL nanoparticles showed a DOX loading content of 5.1 wt% and a loading efficiency of 49%. In vitro drug release studies showed that about 62.4% and 56% of DOX was released from the nanoparticles during 72 h at 37 °C in PBS containing 2 mg/mL (6 mM) GSH and 0.1% H2O2, respectively, whereas only about 30% of DOX was released in PBS under the same conditions. The cell viability (MTT assays) results showed that the synthesized material was biocompatible with above 90% cell viability, and that the DOX-loaded Bi(mPEG-SeSe)-PCL nanoparticles had a high antitumor activity against HeLa cells and low antitumor activity against HaCaT cells, following a 24-h incubation period. Three-dimensional (3D) spheroids of HeLa cells were established for the evaluation of localization of the DOX-loaded nanoparticles into spheroids cells and the successfully inhibition of 3D tumor spheroid growth. The results indicated that the synthesized material Bi(mPEG-SeSe)-PCL was biocompatible and it could be a potential candidate for anticancer drug delivery system.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Compostos de Selênio/química , Antibióticos Antineoplásicos/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Liberação Controlada de Fármacos , Células HeLa , Humanos , Peróxido de Hidrogênio/química , Nanopartículas/administração & dosagem , Oxirredução , Poliésteres/química , Polietilenoglicóis/química , Polímeros/síntese química , Polímeros/farmacocinética , Esferoides Celulares/efeitos dos fármacos , Compostos de Tosil/química
10.
Int J Pharm ; 567: 118486, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31260783

RESUMO

Stimuli-responsive polymeric nanostructures have emerged as potential drug carriers for cancer therapy. Herein, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se2 from mPEG-PLGA and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. Due to its amphiphilic nature, Bi(mPEG-PLGA)-Se2 self-assembled in to stable micelles in aqueous solution with a hydrodynamic size of 123.9 ±â€¯0.85 nm. The Bi(mPEG-PLGA)-Se2 micelles exhibited DOX-loading content (DLC) of 6.61 wt% and encapsulation efficiency (EE) of 54.9%. The DOX-loaded Bi(mPEG-PLGA)-Se2 micelles released 73.94% and 69.54% of their cargo within 72 h upon treatment with 6 mM GSH and 0.1% H2O2, respectively, at pH 7.4 and 37 °C. The MTT assay results demonstrated that Bi(mPEG-PLGA)-Se2 was devoid of any inherent toxicity and the DOX-loaded micelles showed pronounced antitumor activities against HeLa cells, 44.46% of cells were viable at maximum dose of 7.5 µg/mL. The cellular uptake experiment further confirmed the internalization of DOX-loaded Bi(mPEG-PLGA)-Se2 micelles and endowed redox stimuli triggered drug release in cytosol and nuclei of cancer cells. Overall, the results suggested that the smart, biocompatible Bi(mPEG-PLGA)-Se2 copolymer could serve as potential drug delivery biomaterial for the controlled release of hydrophobic drugs in cancer cells.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Poliésteres/administração & dosagem , Polietilenoglicóis/administração & dosagem , Antibióticos Antineoplásicos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Liberação Controlada de Fármacos , Humanos , Micelas , Oxirredução , Poliésteres/química , Polietilenoglicóis/química
11.
Int J Biol Macromol ; 133: 545-563, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31004630

RESUMO

Injectable thermo-responsive hydrogels have been studied for various biomedical applications including; drug delivery, cell encapsulation, and tissue repairing. There are various natural and synthetic polymers which exhibit homogenous injectable solution at ambient temperature and form a gel in human body temperature. Polysaccharide, polypeptide and other biological macromolecule based hydrogels have been getting immense attention in biomedical application due to their low immunogenicity, abundance in nature, high biocompatibility and biodegradability. This manuscript focuses on polysaccharide and polypeptide based thermo-sensitive hydrogels, and some synthetic polymers which forms in situ gel in response to temperature change from ambient to body temperature. The value of numerous reactive functional groups of biological macromolecular polymers has been discussed for effortless modification and design of bio-macromolecule based thermo-sensitive hydrogels. In addition, we emphasized on the basic mechanisms of the thermo-response processes, the strategies to optimize the desired properties and their applications in local delivery approach.


Assuntos
Materiais Biocompatíveis/química , Hidrogéis/química , Peptídeos/química , Polissacarídeos/química , Temperatura , Materiais Biocompatíveis/farmacologia , Humanos , Hidrogéis/farmacologia , Injeções
12.
Macromol Biosci ; 19(5): e1800409, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30821920

RESUMO

Metastasis is a pathogenic spread of cancer cells from the primary site to surrounding tissues and distant organs, making it one of the primary challenges for effective cancer treatment and the major cause of cancer mortality. Heparin-based biomaterials exhibit significant inhibition of cancer cell metastasis. In this study, a non-anticoagulate heparin prodrug is developed for metastasis treatment with a localized treatment system using temperature sensitive, injectable, and biodegradable (poly-(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) polymeric hydrogel. The drug molecule (heparin) is conjugated with the polymer via esterification, and its sustained release is ensured by hydrolysis and polymeric biodegradation. An aqueous solution of the polymer could be used as an injectable solution at below 25 °C and it achieves gel formation at 37 °C. The anti-metastasis effect of the hydrogels is investigated both in vitro and in vivo. The results demonstrated that local administration of injectable heparin-loaded hydrogels effectively promote an inhibitory effect on cancer metastasis.


Assuntos
Anticoagulantes , Portadores de Fármacos , Heparina , Hidrogéis , Neoplasias Experimentais/tratamento farmacológico , Pró-Fármacos , Animais , Anticoagulantes/química , Anticoagulantes/farmacocinética , Anticoagulantes/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Células HeLa , Heparina/química , Heparina/farmacocinética , Heparina/farmacologia , Humanos , Hidrogéis/química , Hidrogéis/farmacocinética , Hidrogéis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Pró-Fármacos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
13.
ACS Biomater Sci Eng ; 5(10): 5453-5469, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33464065

RESUMO

Integrating anticancer drugs and diagnostic agents in a polymer nanosystem is an emerging and promising strategy for improving cancer treatment. However, the development of multifunctional nanoparticles (NPs) for an "all-in-one" platform characterized by specific targeting, therapeutic efficiency, and imaging feedback remains an unmet clinical need. In this study, pH-responsive mixed-lanthanide-based multifunctional NPs were fabricated based on simple metal-ligand interactions for simultaneous cancer cell imaging and drug delivery. We investigated two new systems of alginate-polydopamine complexed with either terbium/europium or dysprosium/erbium oxide NPs (Tb/Eu@AlgPDA or Dy/Er@AlgPDA NPs). Tb/Eu@AlgPDA NPs were then functionalized with the tumor-targeting ligand folic acid (FA) and loaded with the anticancer drug doxorubicin (DOX) to form FA-Tb/Eu@AlgPDA-DOX NPs. Using such systems, the mussel-inspired property of PDA was introduced to improve tumor targetability and penetration, in addition to active targeting (via FA-folate receptor interactions). Determining the photoluminescence efficiency showed that the Tb/Eu@AlgPDA system was superior to the Dy/Er@AlgPDA system, presenting intense and sharp emission peaks on the fluorescence spectra. In addition, compared to Dy/Er@AlgPDA NPs (82.4%), Tb/Eu@AlgPDA NPs exhibited negligible cytotoxicity with >93.3% HeLa cell viability found in MTT assays at NP concentrations of up to 0.50 mg/mL and high biocompatibility when incubated with zebrafish (Danio rerio) embryos and larvae. The FA-Tb/Eu@AlgPDA-DOX system exhibited a pH-responsive and sustained drug-release pattern. In a spheroid model of HeLa cells, the FA-Tb/Eu@AlgPDA-DOX system showed a better penetration efficiency and spheroid growth-inhibitory effect than free DOX. After incubation with zebrafish embryos, the FA-Tb/Eu@AlgPDA-DOX system also showed improved antitumor efficacies versus the other experimental groups in HeLa tumor cell xenografted zebrafish. Therefore, our results suggested that FA-Tb/Eu@AlgPDA-DOX NPs are promising multifunctional nanocarriers with therapeutic capacity for tumor targeting and penetration.

14.
Polymers (Basel) ; 12(1)2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31892144

RESUMO

Polymeric prodrug-based delivery systems have been extensively studied to find a better solution for the limitations of a single drug and to improve the therapeutic and pharmacodynamics properties of chemotherapeutic agents, which can lead to efficient therapy. In this study, redox-responsive disulfide bond-containing amphiphilic heparin-chlorambucil conjugated polymeric prodrugs were designed and synthesized to enhance anti-tumor activities of chlorambucil. The conjugated prodrug could be self-assembled to form spherical vesicles with 61.33% chlorambucil grafting efficiency. The cell viability test results showed that the prodrug was biocompatible with normal cells (HaCaT) and that it selectively killed tumor cells (HeLa cells). The uptake of prodrugs by HeLa cells increased with time. Therefore, the designed prodrugs can be a better alternative as delivery vehicles for the chlorambucil controlled release in cancer cells.

15.
ACS Appl Mater Interfaces ; 10(6): 5147-5160, 2018 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-29277987

RESUMO

Manganese-based nanomaterials are an emerging new class of magnetic resonance imaging (MRI) contrast agents (CAs) that provide impressive contrast abilities. MRI CAs that can respond to pathophysiological parameters such as pH or redox potential are also highly in demand for MRI-guided tumor diagnosis. Until now, synthesizing nanomaterials with good biocompatibility, physiochemical stability, and good contrast effects remains a challenge. This study investigated two new systems of calcium/manganese cations complexed with either alginate-polydopamine or alginate-dopamine nanogels [AlgPDA(Ca/Mn) NG or AlgDA(Ca/Mn) NG]. Under such systems, Ca cations form ionic interactions via carboxylic acids of the Alg backbone to enhance the stability of the synthetic nanogels (NGs). Likewise, complexation of Mn cations also increased the colloidal stability of the synthetic NGs. The magnetic property of the prepared CAs was confirmed with superconducting quantum interference device measurements, proving the potential paramagnetic property. Hence, the T1 relaxivity measurement showed that PDA-complexed synthetic NGs reveal a strong positive contrast enhancement with r1 = 12.54 mM-1·s-1 in 7.0 T MRI images, whereas DA-complexed synthetic NGs showed a relatively lower T1 relaxivity effect with r1 = 10.13 mM-1·s-1. In addition, both the synthetic NGs exhibit negligible cytotoxicity with >92% cell viability up to 0.25 mM concentration, when incubated with the mouse macrophage (RAW 264.7) and HeLa cells, and high biocompatibility under in vivo analysis. The in vivo MRI test indicates that the synthetic NG exhibits a high signal-to-noise ratio for longer hours, which provides a longer image acquisition time for tumor and anatomical imaging. Furthermore, T1-weighted MRI results revealed that PEGylated AlgPDA(Ca/Mn) NGs significantly enhanced the signals from liver and tumor tissues. Therefore, owing to the enhanced permeability and retention effect, significantly enhanced in vitro and in vivo imagings, low cost, and one-pot synthesis method, the Mn-based biomimetic approach used in this study provides a promising and competitive alternative for noninvasive tumor detection and comprehensive anatomical diagnosis.


Assuntos
Nanoestruturas , Ácido Algínico , Animais , Meios de Contraste , Células HeLa , Humanos , Indóis , Imageamento por Ressonância Magnética , Manganês , Camundongos , Polímeros
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