RESUMO
Rhodamine derivatives have been widely investigated for their mitochondrial targeting and chemotherapeutic properties that result from their lipophilic cationic structures. In previous research, we have found that conversion of Rhodamine 6G into nanoGUMBOS, i.e., nanomaterials derived from a group of uniform materials based on organic salts (GUMBOS), led to selective chemotherapeutic toxicity for cancer cells over normal cells. Herein, we investigate the chemotherapeutic activity of GUMBOS derived from four different rhodamine derivatives, two bearing an ester group, i.e., Rhodamine 123 (R123) and SNAFR-5, and two bearing a carboxylic acid group, i.e., rhodamine 110 (R110) and rhodamine B (RB). In this study, we evaluate (1) relative hydrophobicity via octanol-water partition coefficients, (2) cytotoxicity, and (3) cellular uptake in order to evaluate possible structure-activity relationships between these different compounds. Intriguingly, we found that while GUMBOS derived from R123 and SNAFR-5 formed nanoGUMBOS in aqueous medium, no distinct nanoparticles are observed for RB and R110 GUMBOS. Further investigation revealed that the relatively high water solubility of R110 and RB GUMBOS hinders nanoparticle formation. Subsequently, while R123 and SNAFR-5 displayed selective chemotherapeutic toxicity similar to that of previously investigated R6G nanoGUMBOS, the R110 and RB GUMBOS were lacking in this property. Additionally, the chemotherapeutic toxicities of R123 and SNAFR-5 nanoGUMBOS were also significantly greater than R110 and RB GUMBOS. Observed results were consistent with decreased cellular uptake of R110 and RB as compared to R123 and SNAFR-5 compounds. Moreover, these results are also consistent with previous observations that suggest that nanoparticle formation is critical to the observed selective chemotherapeutic properties as well as the chemotherapeutic efficacy of rhodamine nanoGUMBOS.
Assuntos
Nanopartículas/química , Neoplasias/tratamento farmacológico , Rodaminas/química , Linhagem Celular Tumoral , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Neoplasias/patologia , Compostos Orgânicos/química , Compostos Orgânicos/farmacologia , Rodamina 123/química , Rodamina 123/farmacologia , Rodaminas/farmacologia , Solubilidade/efeitos dos fármacos , Água/químicaRESUMO
A novel imidazolium-dysprosium-based magnetic nanomaterial, i.e. [C16mim]5[Dy(SCN)8] nanoGUMBOS (nanomaterials fabricated from a group of uniform material based on organic salts), was prepared using a facile method for selective hemoglobin (Hb) isolation. In this nanomaterial, the imidazolium cation serves as a selective Hb affinity group, while dysprosium contributes paramagnetic properties. Through a combination of the advantages of ionic liquids, magnetic adsorbent, and nanoscale solid phase extraction, [C16mim]5[Dy(SCN)8] nanoGUMBOS exhibit great selectivity toward Hb and a favorable extraction efficiency of 95.4% when 1â¯mL of 100⯵g/mL Hb solution is processed with 0.6â¯mg of [C16mim]5[Dy(SCN)8] nanoGUMBOS. As the Hb concentration increased to 800⯵g/mL, the adsorption capacity approached â¼840⯵g/mg. The adsorbed protein is recovered with an elution efficiency of 87% by using 1% SDS solution. This novel nanoGUMBOS solid-phase extraction procedure was successfully applied to selective isolation of Hb from human whole blood and verified using SDS-PAGE. This simple strategy is a novel approach towards fabrication and use of a nanoadsorbent for selective isolation of proteins.
Assuntos
Disprósio/química , Hemoglobinas/isolamento & purificação , Nanoestruturas/química , Extração em Fase Sólida/métodos , Adsorção , Sangue , Análise Química do Sangue/instrumentação , Análise Química do Sangue/métodos , Dicroísmo Circular , Eletroforese em Gel de Poliacrilamida , Hemoglobinas/química , Humanos , Imidazóis/química , Líquidos Iônicos/química , Fenômenos Magnéticos , Sais/química , Extração em Fase Sólida/instrumentaçãoRESUMO
The near-infrared fluorescent (NIRF) dye, IR780, is recognized as a promising theranostic agent and has been widely investigated for imaging, chemotherapeutic, and phototherapeutic applications. However, its poor photostability and nonselective toxicities toward both cancer and normal cells limit its biological applications. Herein, we introduce the use of GUMBOS (a group of uniform materials based on organic salts) developed through counter-anion exchange with IR780 and subsequent nanomaterials (nanoGUMBOS) formed by complexation with cyclodextrin (CD) for enhanced chemo/photothermal therapy. Such CD-based nanoGUMBOS display improved aqueous stability, photostability, and photothermal effects relative to traditional IR780. The examination of in vitro cytotoxicity reveals that CD-based nanoGUMBOS are selectively toxic toward cancer cells and exhibit synergistically enhanced cytotoxicity toward cancer cells upon NIR laser irradiation. Additionally, in vivo NIRF imaging demonstrated selective accumulation of these nanoGUMBOS within the tumor site, indicating tumor-targeting properties. Further in vivo therapeutic study of these CD-based nanoGUMBOS suggests excellent chemo/photothermal antitumor effects. Using these studies, we herein demonstrate a promising strategy, via conversion of IR780 into nanoGUMBOS, that can be used for improved theranostic cancer treatment.
Assuntos
Neoplasias da Mama/terapia , Sistemas de Liberação de Medicamentos , Corantes Fluorescentes , Hipertermia Induzida , Indóis , Nanopartículas , Fototerapia , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Humanos , Indóis/química , Indóis/farmacologia , Células MCF-7 , Camundongos , Nanopartículas/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Herein, we report on the role of endocytosis in the selective chemotherpeutic toxicity of rhodamine 6G (R6G) based nanomaterials, i.e., nanoGUMBOS, that are derived from a group of uniform materials based on organic salts (GUMBOS). Evaluation of cellular uptake in the presence and absence of endocytosis inhibitors suggests nanoGUMBOS internalization via clathrin-mediated endocytosis in cancer cells and reveals lack of endocytic internalization in normal cells. Results from characterization of these nanomaterials suggest that endocytic internalization in cancer cells leads to nanoGUMBOS dissociation within the endosomal environment. This ultimately results in selective cytotoxicity of the nanoGUMBOS for cancer cells with no toxicity toward normal cells under examined conditions. Following examination of the selectivity mechanism, in vivo investigations were performed to examine potential therapeutic properties of these nanoparticles. Remarkably, nanoGUMBOS treatment using a mouse xenograft model reduced the tumor volume by 50% suggesting retention of in vitro therapeutic properties in vivo. These results corroborate the selective behavior of nanoGUMBOS and demonstrate their in vivo therapeutic effects, providing further insight into the possible use of these nanomaterials as potential chemotherapeutic agents.
Assuntos
Endocitose/efeitos dos fármacos , Nanoestruturas/toxicidade , Rodaminas/toxicidade , Animais , Neoplasias da Mama/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Citometria de Fluxo , Humanos , Camundongos Nus , Nanoestruturas/química , Rodaminas/químicaRESUMO
Molecularly imprinted polymers (MIPs) are an important class of selective materials for molecular specific sensors and separations. Molecular imprinting using non-covalent interactions in aqueous conditions still remains a difficult challenge due to interruption of hydrogen-bonding or electrostatic interactions water. Newly developed crosslinking ionic liquids are demonstrated herein to overcome problems of synthesizing aqueous MIPs, adding to previous examples of ionic liquids used as monomers in non-aqueous conditions or used as MIP solvents. Vinylimidazole ionic liquid crosslinkers were synthesized and subsequently explored as matrix supports for fabrication of molecularly imprinted polymeric nanoGUMBOS (nanoparticles derived from a group of uniform materials based on organic salts). Each of the four crosslinkers incorporated a unique functional spacer between the vinylimidazole groups, and the performance of the corresponding molecularly imprinted polymers was evaluated using chiral recognition as the diagnostic. High uptake values for l-tryptophan were found in the 13-87µmol/g range; and chiral recognition was determined via binding ratios of l-tryptophan over d-tryptophan that ranged from 5:1 to 13:1 for polymers made using different crosslinkers. Not only are these materials good for chiral recognition, but the results highlight the utility of these materials for imprinting aqueous templates such as biological targets for theranostic agents.
RESUMO
Over the past several years, nanomaterials derived from a group of uniform materials based on organic salts (GUMBOS) have been introduced into the scientific literature involving many analytical, biological, and technological applications. In this regard, these nanoGUMBOS have been shown to display a number of unique properties including fluorescence, magnetism, tumor targeting, and optoelectronic. To date, however, little focus has been placed on developing and refining approaches for generation of size-controlled nanoGUMBOS from GUMBOS building blocks. Herein, we describe a systematic effort to define various strategies for the production of well-defined nanoGUMBOS. Specifically, we describe methods based on (i) sonochemical, (ii) microwave-assisted, (iii) cyclodextrin-assisted, and (iv) surfactant-assisted syntheses of nanoGUMBOS, evaluating the efficiency of each technique in controlling the size, sphericity, and uniformity of nanoGUMBOS produced. The effect of systematic variation in experimental parameters such as concentration, cation-to-anion ratio, as well as presence and type of template introduced for formation of nanoGUMBOS is also investigated.