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Dermatophytosis is a prevalent fungal infection and public health burden, majorly caused by the attack of zoophilic fungi genera of Trichophyton and Microsporum. Among them, T. mentagrophytes and M. canis are the dominating pathogens that cause dermatophytosis in humans. Though anti-fungal treatments are available, the widespread drug resistance and minimal efficacy of conventional therapies cause recurring infections. In addition, prolonged anti-fungal medications induce several systemic side effects, including hepatotoxicity and leucopenia. The anti-dermatophytic formulation of biocompatible essential oil components (EOCs) is attractive due to their highly potent anti-dermatophytic action. Herein, two EOCs, Eugenol (EU) and Isoeugenol (IU), incorporated emulsion hydrogel (EOCs-EHG) synthesized from hydroxypropylmethyl cellulose and poly(ethylene glycol) methyl ether methacrylate. The cytocompatibility of the hydrogels is confirmed by treating them with fibroblast and keratinocyte cell lines. The EOCs-EHG demonstrated pH and temperature-responsive sustained release of entrapped EOCs and inhibited fungal spore germination. T. mentagrophytes and M. canis biofilms are eradicated at a minimal inhibitory concentration of 2 µg mL-1 each of EU and IU. The in vivo anti-dermatophytic activity of EOCs-EHG is confirmed in dermatophyte-infected Wistar albino rat models. The topical application of EOCs-EHG demonstrated complete infection eradication and facilitated skin regeneration, emphasizing the therapeutic potential of EOCs-EHG against dermatophytosis.
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Reduced nicotinamide adenine dinucleotide (NADH)-detecting electrochemical sensors are attractive in monitoring and diagnosing various physiological disorders of NADH abnormalities. The NADH detection methods using conventional electrodes are challenging due to slow electron transfer and fouling effect. Interestingly, paper-based flexible and disposable electrodes (PE) are superior for sensing biomolecules through simple detection procedures with excellent sensitivity and selectivity. Herein, to construct a conducting polypeptide-modified paper electrode, initially, polytyrosine (PTyr) is synthesized from l-tyrosine N-carboxy anhydride through ring-opening polymerization, and PTyr is drop-coated on the PE. The PTyr-modified paper electrode (PMPE) demonstrated excellent electrochemical properties and facilitated the electrooxidation of NADH at a lower potential of 576 mV. The PMPE displayed a linear detection between 25 and 145 µM of NADH concentration, with a lower detection limit of 0.340 µM. Under ideal circumstances, the sensor developed displayed an excellent NADH detection capability without interference with the most common electroactive species, ascorbic acid. The PMPE facilitates good electrocatalytic activity toward NADH, which can also be employed as a substrate material for biofuel cells.
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Electrodos , NAD , Papel , NAD/análisis , NAD/química , Péptidos/química , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Oxidación-Reducción , Límite de Detección , Técnicas Biosensibles/métodosRESUMEN
Peptide-based polymers are evolving as promising materials for various biomedical applications. Among peptide-based polymers, polytyrosine (PTyr)-based and l-tyrosine (Tyr)-derived polymers are unique, due to their excellent biocompatibility, degradability, and functional as well as engineering properties. To date, different polymerization techniques (ring-opening polymerization, enzymatic polymerization, condensation polymerization, solution-interfacial polymerization, and electropolymerization) have been used to synthesize various PTyr-based and Tyr-derived polymers. Even though the synthesis starts from Tyr, different synthesis routes yield different polymers (polypeptides, polyarylates, polyurethanes, polycarbonates, polyiminocarbonate, and polyphosphates) with unique functional characteristics, and these polymers have been successfully used for various biomedical applications in the past decades. This Review comprehensively describes the synthesis approaches, classification, and properties of various PTyr-based and Tyr-derived polymers employed in drug delivery, tissue engineering, and biosensing applications.
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Polímeros , Tirosina , Polímeros/química , Tirosina/química , Materiales Biocompatibles/química , Ingeniería de Tejidos/métodos , Péptidos , PolimerizacionRESUMEN
The present study aims to synthesize and characterize two quaternary ammonium (QAM) based monomers such as - dimethyl-hexadecyl-methacryloxyethyl-ammonium iodide (DHMAI) and 2-dimethyl-2-dodecyl-1-methacryloxyethyl ammonium iodine (DDMAI) and assess their cytotoxicity and antimicrobial properties. The study also aims to incorporate the optimized concentration of these monomers as copolymerizing monomers into conventional Polymethyl methacrylate (PMMA) denture base resin and evaluate their suitability for prosthetic applications. DHMAI and DDMAI monomers were synthesized through a Menschutkin reaction and their chemical structure was characterized using FT-IR and 1H-NMR spectroscopy. Cytotoxicity was determined using Methyl Thiazolyl Tetrazolium (MTT) assay whereas antimicrobial activity was assessed using the agar-disc diffusion method. Subsequently, optimized concentrations of DHMAI or DDMAI, based on the cytotoxicity results, were added to conventional PMMA resin. Antimicrobial activity, cytotoxicity, surface hardness, and water sorption of PMMA denture base rein incorporated with DHMAI or DDMAI were evaluated. FT-IR and 1H-NMR results confirmed the structure of monomers and copolymerization of DHMAI and DDMAI with PMMA resin. DHMAI and DDMAI monomers were found to be cytocompatible with mouse fibroblast cells up to a concentration of 5 µg/mL and 20 µg/mL respectively. In addition, incorporation of DHMAI or DDMAI at 5 µg/mL and 20 µg/mL respectively into PMMA denture base material did not affect their cytocompatibility. PMMA denture base resin incorporated with DHMAI or DDMAI significantly reduced the adhesion of microbes. Further, an increase in the surface hardness and a reduction in the water sorption was observed. Hence DHMAI and DDMAI can be considered as potential candidates for imparting antimicrobial activity to polymeric denture base materials.
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Prostate cancer (PC) is the most prevalent male urogenital cancer worldwide. PC patients presenting an advanced or metastatic cancer succumb to the disease, even after therapeutic interventions including radiotherapy, surgery, androgen deprivation therapy (ADT), and chemotherapy. One of the hallmarks of PC is evading immune surveillance and chronic inflammation, which is a major challenge towards designing effective therapeutic formulations against PC. Chronic inflammation in PC is often characterized by tumor microenvironment alterations, epithelial-mesenchymal transition and extracellular matrix modifications. The inflammatory events are modulated by reactive nitrogen and oxygen species, inflammatory cytokines and chemokines. Major signaling pathways in PC includes androgen receptor, PI3K and NF-κB pathways and targeting these inter-linked pathways poses a major therapeutic challenge. Notably, many conventional treatments are clinically unsuccessful, due to lack of targetability and poor bioavailability of the therapeutics, untoward toxicity and multidrug resistance. The past decade witnessed an advancement of nanotechnology as an excellent therapeutic paradigm for PC therapy. Modern nanovectorization strategies such as stimuli-responsive and active PC targeting carriers offer controlled release patterns and superior anti-cancer effects. The current review initially describes the classification, inflammatory triggers and major inflammatory pathways of PC, various PC treatment strategies and their limitations. Subsequently, recent advancement in combinatorial nanotherapeutic approaches, which target PC inflammatory pathways, and the mechanism of action are discussed. Besides, the current clinical status and prospects of PC homing nanovectorization, and major challenges to be addressed towards the advancement PC therapy are also addressed.
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Neoplasias de la Próstata , Receptores Androgénicos , Antagonistas de Andrógenos/uso terapéutico , Andrógenos/uso terapéutico , Citocinas , Preparaciones de Acción Retardada/uso terapéutico , Humanos , Inflamación/tratamiento farmacológico , Masculino , FN-kappa B , Nitrógeno/uso terapéutico , Oxígeno/uso terapéutico , Fosfatidilinositol 3-Quinasas/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Receptores Androgénicos/metabolismo , Receptores Androgénicos/uso terapéutico , Microambiente TumoralRESUMEN
Quorum sensing mediated biofilm formation has a major role in modern therapeutics due to adherence of cells on the solid surface. Here, we have developed a stable polyurethane blend with a 6-methylcoumarin (6-MC) composite that showed significant antibiofilm activity. The 6-MC was found to prominently inhibit P. aeruginosa PAO1 biofilm formation at 125 µg/ml and was able to inhibit various virulence factors such as pyocyanin, siderophore, exopolysaccharide, elastase and proteases, including motility of the bacteria. In addition, 6-MC was found functionally active in saving the C. elegans from P. aeruginosa PAO1 infection. Moreover, docking studies of different activator proteins correlate well with in vitro and in vivo results. To enhance this biological activity, 6-MC was blended with polyurethane, which also revealed superior antibiofilm activity on plastic and glass surfaces compared to a polyurethane coating. Therefore, the 6-MC could be used to combat P. aeruginosa infection for effective treatment and antibiofilm applications on solid surfaces through polyurethane blending and subsequent film fabrication strategies. KEY POINTS: ⢠6-Methylcoumarin significantly inhibits P. aeruginosa PAO1 biofilm ⢠6-MC was found functionally active in saving the C. elegans from PAO1 infection ⢠6-MC and polyurethane blend showed superior antibiofilm activity.
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Pseudomonas aeruginosa , Percepción de Quorum , Animales , Antibacterianos/farmacología , Biopelículas , Caenorhabditis elegans , Cumarinas , Poliuretanos , Factores de VirulenciaRESUMEN
"Smart" polymeric nanoformulations are evolving as a promising therapeutic, diagnostic paradigm. The polymeric nanovehicles demonstrated excellent capability to encapsulate theranostic cargos and their successful delivery in physiological conditions and even to monitor the therapeutic response. Currently, polymer nanogels (NGs) are established as capable carriers toward triggered delivery of diverse therapeutic and diagnostic agents. Notably, biodegradable and "intelligent" NGs constructed from intelligent polymers are highly beneficial because of their responsiveness toward endogenous as well as exogenous stimuli like pH gradients, bioresponsiveness, photoresponsiveness, temperature, and so on. In the past decade, plenty of multifunctional NGs with excellent targetability and sensitivity were reported for a wide range of theragnostic applications. This mini-review briefly propounds the synthesis strategies of "smart" NGs and summarizes the notable applications like delivery of genetic materials, anticancer agents, photodynamic/photothermal therapies, imaging, and biosensing. Herein, we have also addressed the current clinical status of NGs and the major challenges that are essential to overcome for the further advancement of NGs for specific applications.
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Polymer nanogels (NGs) are water-swellable, cross-linked 3D network structures with size typically range from 1 to 1000 nm. Especially, biocompatible and "smart" NGs engineered from stimuli-responsive polymers are attractive because of its capability to respond the endogenous biological triggers of pH, bioreduction, biomolecule recognition, as well as the exogenous stimuli-triggers like temperature and light. Importantly, on exposing to these physical or biochemical signals, the responsive NGs can be utilized for therapeutic delivery and diagonostic applications. In the past decade, substantial developments were achieved in the development of "smart" NGs for theranostic and diagnostic applications such as intracellular delivery of drug and nucleic acids, photodynamic/photothermal therapy, bioimaging and sensing. Herein, we exclusively review the recent exciting developments in synthetic methods as well as biomedical applications of successfully employed "smart" NGs which can respond to a single, dual or multiple stimulus- responsive triggers. The prospects in the application of the stimuli-responsive and multifunctional NGs also will be addressed in this review.
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Portadores de Fármacos , Técnicas de Transferencia de Gen , Imagen Molecular , Nanogeles , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Polímeros de Estímulo Receptivo/química , Nanomedicina Teranóstica , Animales , Humanos , Concentración de Iones de Hidrógeno , Luz , Neoplasias/genética , Polímeros de Estímulo Receptivo/efectos de la radiación , TemperaturaRESUMEN
Injectable, drug-releasing hydrogel scaffolds with multifunctional properties including hemostasis and anti-bacterial activity are essential for successful wound healing; however, designing ideal materials is still challenging. Herein, we demonstrate the fabrication of a biodegradable, temperature-pH dual responsive supramolecular hydrogel (SHG) scaffold based on sodium alginate/poly(N-vinyl caprolactam) (AG/PVCL) through free radical polymerization and the subsequent chemical and ionic cross-linking. A natural therapeutic molecule, tannic acid (TA)-incorporated SHG (AG/PVCL-TA), was also fabricated and its hemostatic and wound healing efficiency were studied. In the AG/PVCL-TA system, TA acts as a therapeutic molecule and also substitutes as an effective gelation binder. Notably, the polyphenol-arm structure and diverse bonding abilities of TA can hold polymer chains through multiple bonding and co-ordinate cross-linking, which were vital in the formation of the mechanically robust AG/PVCL-TA. The SHG formation was successfully balanced by varying the composition of SA, VCL, TA and cross-linkers. The AG/PVCL-TA scaffold was capable of releasing a therapeutic dose of TA in a sustained manner under physiological temperature-pH conditions. AG/PVCL-TA displayed excellent free radical scavenging, anti-inflammatory, anti-bacterial, and cell proliferation activity towards the 3T3 fibroblast cell line. The wound healing performance of AG/PVCL-TA was further confirmed in skin excision wound models, which demonstrated the potential application of AG/PVCL-TA for skin regeneration and rapid wound healing.
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Antibacterianos/uso terapéutico , Hemostasis/efectos de los fármacos , Hidrogeles/química , Taninos/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Alginatos/química , Alginatos/toxicidad , Animales , Antibacterianos/química , Antibacterianos/toxicidad , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Antiinflamatorios/toxicidad , Antioxidantes/química , Antioxidantes/uso terapéutico , Antioxidantes/toxicidad , Bacterias/efectos de los fármacos , Caprolactama/análogos & derivados , Caprolactama/química , Caprolactama/toxicidad , Movimiento Celular/efectos de los fármacos , Femenino , Hidrogeles/toxicidad , Concentración de Iones de Hidrógeno , Inflamación/tratamiento farmacológico , Ratones , Pruebas de Sensibilidad Microbiana , Células 3T3 NIH , Polímeros/química , Polímeros/toxicidad , Ratas Wistar , Piel/patología , Taninos/química , Taninos/toxicidad , TemperaturaRESUMEN
Calcium is the key macromineral having a role in skeletal structure and function, muscle contraction, and neurotransmission. Bone remodeling is maintained through a constant balance between calcium resorption and deposition. Calcium deficiency is resolved through calcium supplementation, and among the supplements, water-soluble organic molecules attracted great pharmaceutical interest. Calcium glucoheptonate is a highly water-soluble organic calcium salt having clinical use; however, detailed investigations on its biological effects are limited. We assessed the effects of calcium glucoheptonate on cell viability and proliferation of osteoblast-like MG-63 cells. Calcium uptake and mineralization were evaluated using Alizarin red staining of osteoblast-like MG-63 cells treated with calcium glucoheptonate. Expression of osteogenic markers were monitored by western blotting, immunofluorescence, and qRT-PCR assays. Increased proliferation and calcium uptake were observed in the MG-63 cells treated with calcium glucoheptonate. The treatment also increased the expression of osteopontin and osteogenic genes such as collagen-1, secreted protein acidic and cysteine rich (SPARC), and osteocalcin. Calcium glucoheptonate treatment did not exert any cytotoxicity on colorectal and renal epithelial cells, indicating the safety of the treatment. This is the first report with evidence for its beneficial effect for pharmaceutical use in addressing calcium deficiency conditions.
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Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Azúcares Ácidos/farmacología , Células CACO-2 , Calcio/metabolismo , Línea Celular Tumoral , Células Cultivadas , Colágeno Tipo I/metabolismo , Células HEK293 , Humanos , Osteoblastos/citología , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Osteonectina/metabolismo , Osteopontina/metabolismoRESUMEN
Smart delivery system of photosensitizer chlorin e6 (Ce6) has been developed for targeted photodynamic therapy (PDT). Simple self-assemblies of the mixtures comprising soybean lecithin derived phosphatidylcholine (PC), phosphatidylethanolamine-poly(L-histidine)40 (PE-p(His)40), and folic acid (FA) conjugated phosphatidylethanolamine-poly(N-isopropylacrylamide)40 (PE-p(NIPAM)40-FA) in different ratios yield smart nanospheres characterized by (i) stable and uniform particle size (â¼100 nm), (ii) positive surface charge, (iii) high hydrophobic drug (Ce6) loading efficiency up to 45%, (iv) covalently linked targeting moiety, (v) low cytotoxicity, and (vi) smartness showing p(His) block oriented pH and p(NIPAM) oriented temperature responsiveness. The Ce6-encapsulated vesicular nanospheres (Ce6@VNS) were used to confirm the efficiency of cellular uptake, intracellular distribution, and phototoxicity against KB tumor cells compared to free Ce6 at different temperature and pH conditions. The Ce6@VNS system showed significant photodynamic therapeutic efficiency on KB cells than free Ce6. A receptor-mediated inhibition study proved the site-specific delivery of Ce6 in targeted tumor cells.
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Nanosferas/administración & dosificación , Nanosferas/química , Neoplasias/tratamiento farmacológico , Polímeros/administración & dosificación , Polímeros/química , Acrilamidas/química , Línea Celular Tumoral , Clorofilidas , Histidina/química , Humanos , Células KB , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/química , Porfirinas/químicaRESUMEN
A series of poly(ethylene glycol) methyl ether acrylate-block-poly(L-lysine)-block-poly(L-histidine) [p(PEGA)30-b-p(Lys)25-b-p(His)n] (n = 25, 50, 75, 100) triblock copolypeptides were designed and synthesized for tumoral pH-responsive intracellular release of anticancer drug doxorubicin hydrochloride (Dox). The tumoral acidic pH-responsive hybrid vesicles fabricated were stable at physiological pH 7.4 and could gradually destabilize in acidic pH as a result of pH-induced swelling of the p(His) block. The blank vesicles were nontoxic over a wide concentration range (0.01-100 µg/mL) in normal cell lines. The tumor acidic pH responsiveness of these vesicles was exploited for intracellular delivery of Dox. Vesicles efficiently encapsulated Dox, and pH-induced destabilization resulted in the controlled and sustained release of Dox in CT26 murine cancer cells, and dose-dependent cytotoxicity. The tumor-specific controlled release Dox from vesicles demonstrates this system represents a promising theranostic agent for tumor-targeted delivery.
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Antineoplásicos/farmacocinética , Doxorrubicina/farmacocinética , Portadores de Fármacos/farmacocinética , Nanoestructuras/química , Polietilenglicoles/química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/química , Doxorrubicina/farmacología , Portadores de Fármacos/química , Portadores de Fármacos/farmacología , Histidina/química , Concentración de Iones de Hidrógeno , Ratones , Células 3T3 NIH , Nanoestructuras/toxicidad , Polilisina/químicaRESUMEN
Stimuli-responsive nanocarriers are a class of soft materials that includes natural polymers, synthetic polymers, and polypeptides. Recently, modern synthesis tools such as atom transfer radical polymerization, reversible addition-fragmentation chain transfer polymerization, nitroxide-mediated radical polymerization, ring-opening polymerization of α-amino acid N-carboxyanhydrides, and various "click" chemistry strategies were simultaneously employed for the design and synthesis of nanosized drug delivery vehicles. Importantly, the research focused on the improvement of the nanocarrier targetability and the site-specific, triggered release of therapeutics with high drug loading efficiency and minimal drug leakage during the delivery to specific targets. In this context, nanocarriers responsive to common stimuli such as pH, temperature, redox potential, light, etc. have been widely used for the controlled delivery of therapeutics to pathological sites. Currently, different synthesis and self-assembly strategies improved the drug loading efficacy and targeted delivery of therapeutic agents to the desired site. In particular, polypeptide-containing hybrid materials have been developed for the controlled delivery of therapeutic agents. Therefore, stimuli-sensitive synthetic polypeptide-based materials have been extensively investigated in recent years. This review focuses on recent advances in the development of polymer-block-polypeptides and polymer-conjugated hybrid materials that have been designed and evaluated for various stimuli-responsive drug and gene delivery applications.
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Preparaciones de Acción Retardada/síntesis química , Nanocápsulas/química , Nanocompuestos/química , Péptidos/química , Polímeros/química , Composición de Medicamentos/métodos , Calor , Concentración de Iones de Hidrógeno , Luz , Nanocápsulas/ultraestructura , Nanocompuestos/ultraestructura , Estrés MecánicoRESUMEN
A series of temperature-responsive lipopolymers have been synthesized by bioconjugating poly(N-isopropylacrylamide)n (n = 25, 40, 60) onto three different phospholipids by the combination of reversible addition fragmentation chain transfer polymerization and azide-alkyne click reactions. To achieve the active targeting of cancer cells, folic acid (FA) has also been tethered to the resulting hybrid materials. The doxorubicin (Dox) encapsulated uniform nanocarriers (150 nm in diameter) fabricated by the self-assembly of the lipopolymers display temperature responsive controlled release. The FA receptor-mediated delivery of Dox was then assessed using KB cell lines, and the anti-cancer activity was assessed by the blocking of folic acid receptors. The FA-tethered lipopolymers showing temperature-responsiveness are advantageous for the cell-specific release of Dox, potentiating their anti-cancer activity.
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In order to develop efficient and nontoxic gene delivery vectors, a series of biocompatible block copolymers, poly[(2-hydroxyethyl methacrylate)40 -block-(L-lysine)n ] (n = 40, 80, 120, 150), are prepared by combining an atom transfer radical polymerization of 2-hydroxyethyl methacrylate with a ring-opening polymerization of N(ϵ) -(carbobenzoxy)-L-lysine N-carboxyanhydride. The block copolymers are successfully condensed with plasmid DNA (pDNA) into nanosized (<200 nm) polyplexes. As a representative sample, p(HEMA)40 -b-p(lys)150 is utilized to confirm the effective cellular and nuclear uptake of pDNA. The polymer/pDNA polyplexes exhibit very low cytotoxicity and enhanced transfection activity by being easily taken up into mouse embryonic fibroblast cell line (NIH 3T3). Thus, the chimeric block copolymers provide a means for developing versatile nonviral gene vectors harboring the ideal requirements of low cytotoxicity, good stability, and high transfection efficiency for gene therapy.
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Técnicas de Transferencia de Gen , Vectores Genéticos , Nanopartículas/química , Plásmidos , Polihidroxietil Metacrilato , Polilisina , Animales , ADN/química , ADN/farmacología , Vectores Genéticos/química , Vectores Genéticos/farmacología , Ratones , Células 3T3 NIH , Plásmidos/química , Plásmidos/farmacología , Polihidroxietil Metacrilato/química , Polihidroxietil Metacrilato/farmacología , Polilisina/química , Polilisina/farmacologíaRESUMEN
Biocompatible lipo-histidine hybrid materials conjugated with IR820 dye show pH-sensitivity, efficient intracellular delivery of doxorubicin (Dox), and intrinsic targetability to cancer cells. These new materials form highly uniform Dox-loaded nanosized vesicles via a self-assembly process showing good stability under physiological conditions. The Dox-loaded micelles are effective for suppressing MCF-7 tumors, as demonstrated in vitro and in vivo. The combined mechanisms of the EPR effect, active internalization, endosomal-triggered release, and drug escape from endosomes, and a long blood circulation time, clearly prove that the IR820 lipopeptide DDS is a safe theranostic agent for imaging-guided cancer therapy.
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Histidina/química , Concentración de Iones de Hidrógeno , Humanos , Células MCF-7 , Microscopía Electrónica de TransmisiónRESUMEN
Fluorescent cut single-walled carbon nanotube (CSWCNT) were prepared by simply mixing CSWCNT with water soluble rhodamine 6G (Rh6G) conjugated poly(3,4-dihydroxyphenylalanine) and poly(L-tyrosine) to form highly stable product with good dispersity in buffer solution. The optical absorbance and fluorescence spectra of the resulting fluorescent CSWCNT display interesting pH-dependent optical properties, emitting strong fluorescence only in acidic environment. Considering the extracellular pH of tumor tissue is acidic, the pH-sensitive conjugates have advantages to sense tumor cells selectively, enabling it to be utilized as a biosensor for detecting cancer cells. The protocol employed to functionalize the CSWCNT with Rh6G conjugated polypeptides in aqueous solution is proven to be direct, fast and easily scalable.
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Técnicas Biosensibles/métodos , Concentración de Iones de Hidrógeno , Nanotubos de Carbono/química , Péptidos/química , Rodaminas/análisis , Rodaminas/química , Espectrometría de Fluorescencia/métodos , Absorción , Sustancias Macromoleculares/química , Ensayo de Materiales , Conformación Molecular , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
A series of dual stimuli responsive synthetic polymer bioconjugate chimeric materials, poly(N-isopropylacrylamide)55-block-poly(L-histidine)n [p(NIPAM)55-b-p(His)n] (n=50, 75, 100, 125), have been synthesized by employing reversible addition-fragmentation chain transfer polymerization of NIPAM, followed by ring-opening polymerization of α-amino acid N-carboxyanhydrides. The dual stimuli responsive properties of the resulting biocompatiable and membrenolytic p(NIPAM)55-b-p(His)n polymers are investigated for their use as a stimuli responsive drug carrier for tumor targeting. Highly uniform self-assembled micelles (â¼55 nm) fabricated by p(NIPAM)55-b-p(His)n polymers display sharp thermal and pH responses in aqueous media. An anticancer drug, doxorubicin (Dox), is effectively encapsulated in the micelles and the controlled Dox release is investigated in different temperature and pH conditions. Antitumor effect of the released Dox is also assessed using the HepG2 human hepatocellular carcinoma cell lines. Dox molecules released from the [p(NIPAM)55-b-p(His)n] micelles remain biologically active and have stimuli responsive capability to kill cancer cells. The self-assembling ability of these hybrid materials into uniform micelles and their efficiency to encapsulate Dox makes them a promising drug carrier to cancer cells. The new chimeric materials thus display tunable properties that can make them useful for a molecular switching device and controlled drug delivery applications needing responses to temperature and pH for the improvement of cancer chemotherapy.