RESUMO
We have developed a simple route for the preparation of aminophenylboronic acid polymer nanoparticles (APB PNs) from 3-aminophenylboronic acid and formaldehyde under alkaline conditions according to an extended StÓ§ber method. Insulin and R6G have been selected to prepare functional insulin-APB PNs and R6G-APB PNs, respectively. During the formation of APB PNs, the representative molecules are embedded inside the APB PNs. Through specific binding of glucose with boronic acid moieties on the R6G-APB PNs and insulin-APB PNs, glucose induces expansion of the APB PNs, leading to release of R6G and insulin molecules, respectively. As a result of release of R6G molecules, the fluorescence intensity of R6G-APB PN solution increases, allowing quantitation of glucose in PBS solutions (10 mM, pH 7.4) with a linear range over 0-10 mM. Release of insulin from insulin-APB PNs is significant and rapid when the glucose concentration is higher than 7 mM. Having advantages of low cost, simple preparation, biocompatibility, and continuous response to glucose, the insulin-APB PNs hold great potential as an alternative for treating diabetic patients. Graphical Abstract Quantitation of glucose and release of insulin by glucose responsive 3-aminophenylboronic acid polymer nanoparticles.
Assuntos
Glicemia/análise , Ácidos Borônicos/química , Corantes Fluorescentes/química , Insulina/análise , Nanopartículas/química , Rodaminas/química , Adulto , Feminino , Humanos , Insulina/administração & dosagem , Nanopartículas/ultraestrutura , Espectrometria de Fluorescência/métodosRESUMO
We have developed a simple, sensitive, and rapid fluorescence assay for the detection of cancer cells, based on "turn-on" retro-self-quenched fluorescence inside the cells. 1,3-Phenylenediamine resin (DAR) nanoparticles (NPs) containing rhodamine 6G (R6G) are conjugated with aptamer (apt) sgc8c to prepare sgc8c-R6GDAR NPs, while that containing rhodamine 101 (R101) are conjugated with TD05 for the preparation of TD05-R101DAR NPs. The sgc8c-R6GDAR and TD05-R101DAR NPs separately recognize CCRF-CEM and Ramos cells. The fluorescence intensities of the two apt-DAR NPs are both weak due to self-quenching, but they increase inside the cells as a result of release of the fluorophores from the apt-DAR NPs. The apt-DAR NPs' structure becomes less compact at low pH value, leading to the release of the fluorophores. The sgc8c-R6GDAR and TD05-R101DAR NPs allow detection of as low as 44 CCRF-CEM cells and 79 Ramos cells mL(-1), respectively, using a commercial reader within 10 min. Practicality of the two probes have been validated by the quantitation and identification of CCRF-CEM and Ramos cells spiked in blood samples through conventional fluorescence and flow cytometry analysis, with advantages of sensitivity, selectivity, and rapidity.
Assuntos
Aptâmeros de Nucleotídeos/química , Separação Celular/métodos , Fluorescência , Nanopartículas/química , Neoplasias/patologia , Polímeros/química , Animais , Humanos , Camundongos , Células NIH 3T3 , Neoplasias/diagnóstico , Células Tumorais CultivadasRESUMO
Developing novel multifunctional nanoparticles (NPs) with robust preparation, low cost, high stability, and flexible functionalizability is highly desirable. This study provides an innovative platform, termed unibody core-shell (UCS), for this purpose. UCS is comprised of two covalent-bonded polymers differed only by the functional groups at the core and the shell. By conjugating Gd(3+) at the stable core and encapsulating doxorubicin (Dox) at the shell in a pH-sensitive manner, we developed a theranostic NPs (UCS-Gd-Dox) that achieved a selective drug release (75% difference between pH 7.4 and 5.5) and MR imaging (r1 = 0.9 and 14.5 mm(-1) s(-1) at pH 7.4 and 5.5, respectively). The anti-cancer effect of UCS-Gd-Dox is significantly better than free Dox in tumor-bearing mouse models, presumably due to enhanced permeability and retention effect and pH-triggered release. To the best of our knowledge, this is the simplest approach to obtain the theranostic NPs with Gd-conjugation and Dox doping.
Assuntos
Sistemas de Liberação de Medicamentos , Imageamento por Ressonância Magnética , Nanopartículas/uso terapêutico , Polímeros/uso terapêutico , Animais , Feminino , Gadolínio , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células NIH 3T3 , Nanopartículas/ultraestrutura , Fatores de TempoRESUMO
A simple hydrothermal method was applied to prepare carbon nanodots (C dots) from o-phenylenediamine (OPD). The C dots exhibit photoluminescence at 567 nm when excited at 420 nm. In the presence of Cu(2+) ions, the colour of C dots changes from yellow to orange, with an increased PL intensity as a result of the formation of Cu(OPD)2 complexes on the surfaces of C dots. The D-band to G-band ratios of C dots in the absence and presence of 80 nM Cu(2+) ions are 1.31 and 4.75, respectively. The C dots allow the detection of Cu(2+) ions with linearity over a concentration range of 2-80 nM, with a limit of detection of 1.8 nM at a signal-to-noise ratio of 3. The cell viability values of A549, MCF-10A, and MDA-MB-231 cells treated with 3 µg mL(-1) of C dots are all greater than 99%, showing their great biocompatibility. Having great water dispersibility, photostability, chemical stability (against NaCl up to 0.5 M), great selectivity, and biocompatibility, the C dots have been employed for the localization of Cu(2+) ions in the cancer cells (A549 cells) treated with 10 µM Cu(2+) ions.
Assuntos
Cobre/química , Nanotubos de Carbono/química , Fenilenodiaminas/química , Materiais Biocompatíveis/química , Carbono/química , Linhagem Celular Tumoral , Sobrevivência Celular , Elétrons , Humanos , Íons , Microscopia Eletrônica de Transmissão , Nanotecnologia , Razão Sinal-Ruído , Cloreto de Sódio , ÁguaRESUMO
A facile, one-pot synthetic approach has been developed for the preparation of BSA-Ce/Au NCs. The fluorescence intensities of BSA-Ce/Au NCs at 410 and 650 nm are pH dependent and independent, respectively. The fluorescence intensity ratio (I410/I650) is linear against pH values from 6.0 to 9.0. These stable and biocompatible BSA-Ce/Au NCs have been used as ratiometric probes for monitoring local pH values inside HeLa cells.
RESUMO
Fluorescent carbon nanodots (C-dots; 4.3 ± 0.8 nm) from fresh tender ginger juice provide high suppression of the growth of human hepatocellular carcinoma cells (HepG2), with low toxicity to normal mammary epithelial cells (MCF-10A) and normal liver cells (FL83B). The inhibition is selective to HepG2 over other tested cancer cells, including human lung cancer cell line (A549), human breast cancer cell line (MDA-MB-231), and human cervical cancer cell line (HeLa). Western blot results reveal that the C-dots up-regulate the expression of p53 protein only in the HepG2 cell line. The 50% inhibiting concentration (IC50) value of the C-dots on HepG2 cells is 0.35 mg mL-1. Image cytometry results show significant uptake of C-dots by HepG2 cells that induce intracellular production of reactive oxygen species (ROS, 18.2-fold increased), while other cells remain almost the same in ROS levels after treatment with C-dots (1.11 mg mL-1). The C-dots trigger the pro-apoptotic factor to promote HepG2 cell apoptosis. The C-dots effectively inhibit the growth of tumors in nude mice (104 ± 14 vs. 3.7 ± 0.2 mg with and without treatment within 14 days).
RESUMO
Polymeric fluorescent nanoparticles, R6GDARs, containing rhodamine 6G within 1,3-phenylenediamine resin are prepared using the extensive Stöber method. The R6GDAR is capable of sensing intracellular pH in living cells, with the fluorescence intensity increasing upon decreasing the pH values from 8.0 to 3.0. This fluorescence enhancement at low pH is based on the "retro-self-quenching" mechanism, where the protonation of the R6GDAR backbones expands the particle structure, leading to increase in the separation among concentrated R6G molecules as well as their release. Fluorescence time-course measurement shows that even individual R6GDARs have high sensitivity to report the environmental pH at the single particle level. Compared to other existing pH sensors, R6GDARs offer a wider working pH range (5 pH units), higher sensitivity, and greater photostability. R6GDARs have been demonstrated to be sensitive to map local pH values inside MCF7 and MDA-MB-231 cells, with extremely low cell toxicity. R6GDARs serve as an excellent pH sensing probe for cellular microenvironments.