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1.
Signal Transduct Target Ther ; 8(1): 418, 2023 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-37919282

RESUMEN

Smart nanoparticles, which can respond to biological cues or be guided by them, are emerging as a promising drug delivery platform for precise cancer treatment. The field of oncology, nanotechnology, and biomedicine has witnessed rapid progress, leading to innovative developments in smart nanoparticles for safer and more effective cancer therapy. In this review, we will highlight recent advancements in smart nanoparticles, including polymeric nanoparticles, dendrimers, micelles, liposomes, protein nanoparticles, cell membrane nanoparticles, mesoporous silica nanoparticles, gold nanoparticles, iron oxide nanoparticles, quantum dots, carbon nanotubes, black phosphorus, MOF nanoparticles, and others. We will focus on their classification, structures, synthesis, and intelligent features. These smart nanoparticles possess the ability to respond to various external and internal stimuli, such as enzymes, pH, temperature, optics, and magnetism, making them intelligent systems. Additionally, this review will explore the latest studies on tumor targeting by functionalizing the surfaces of smart nanoparticles with tumor-specific ligands like antibodies, peptides, transferrin, and folic acid. We will also summarize different types of drug delivery options, including small molecules, peptides, proteins, nucleic acids, and even living cells, for their potential use in cancer therapy. While the potential of smart nanoparticles is promising, we will also acknowledge the challenges and clinical prospects associated with their use. Finally, we will propose a blueprint that involves the use of artificial intelligence-powered nanoparticles in cancer treatment applications. By harnessing the potential of smart nanoparticles, this review aims to usher in a new era of precise and personalized cancer therapy, providing patients with individualized treatment options.


Asunto(s)
Nanopartículas del Metal , Nanotubos de Carbono , Neoplasias , Humanos , Oro/uso terapéutico , Inteligencia Artificial , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Péptidos
2.
Drug Resist Updat ; 68: 100954, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36905712

RESUMEN

The problem of drug resistance due to long-term use of antibiotics has been a concern for years. As this problem grows worse, infections caused by multiple bacteria are expanding rapidly and are extremely detrimental to human health. Antimicrobial peptides (AMPs) are a good alternative to current antimicrobials with potent antimicrobial activity and unique antimicrobial mechanisms, which have advantages over traditional antibiotics in fighting against drug-resistant bacterial infections. Currently, researchers have conducted clinical investigations on AMPs for drug-resistant bacterial infections while integrating new technologies in the development of AMPs, such as changing amino acid structure of AMPs and using different delivery methods for AMPs. This article introduces the basic properties of AMPs, deliberates the mechanism of drug resistance in bacteria and the therapeutic mechanism of AMPs. The current disadvantages and advances of AMPs in combating drug-resistant bacterial infections are also discussed. This article provides important insights into the research and clinical application of new AMPs for drug-resistant bacterial infections.


Asunto(s)
Antiinfecciosos , Infecciones Bacterianas , Humanos , Péptidos Antimicrobianos , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Antiinfecciosos/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias/metabolismo
4.
Nanoscale ; 13(45): 19123-19132, 2021 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-34778894

RESUMEN

Visible blue light exerts microbicidal effects with reduced deleterious effects compared with UV light. However, the lack of specific photosensitizers restricts the use of blue light on wound tissues. Here, we report the use of biomimetic ferrihydrite nanoparticles (Fhn) as the sensitizer to augment not only the antimicrobial but also the healing effects of blue light on S. aureus-infected wound tissue. Based on the excellent photo-Fenton active Fhn under blue light illumination (450 nm, 35 630 lux), the Fhn-sensitized blue-light therapy completely cured acute wound within 7 days in sessions of one hour per day and diminished bacterial and fungal colony-forming units more than 5 log (99.999%) and 2 log (99%) in vitro. Mechanistic studies revealed that hydroxyl radicals (˙OH) generated by the combined therapy could effectively damage the microbe genome and membranes without significant damage to wound tissues. Interestingly, these two naturally occurring nonantibiotic modalities (Fhn with blue light) significantly stimulate the angiogenesis and decrease the inflammatory response on the wound site, which accelerates the wound healing synergically. The results demonstrated the use of biomimetic Fhn as the general photosensitizer for enhanced antimicrobial, anti-inflammatory and wound healing effects of blue light-based therapy.


Asunto(s)
Nanopartículas , Fármacos Fotosensibilizantes , Compuestos Férricos , Luz , Fármacos Fotosensibilizantes/farmacología , Staphylococcus aureus , Cicatrización de Heridas
5.
Nanomaterials (Basel) ; 11(10)2021 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-34685197

RESUMEN

Recent advances in nanotechnology have opened up new avenues for the controlled synthesis of nanoparticles for biomedical and pharmaceutical applications. Chinese herbal medicine is a natural gift to humanity, and it has long been used as an antibacterial and anticancer agent. This study will highlight recent developments in the phytonanotechnological synthesis of Chinese herbal medicines to utilize their bioactive components in biomedical and therapeutic applications. Biologically synthesized silver nanoparticles (AgNPs) have emerged as a promising alternative to chemical and physical approaches for various biomedical applications. The comprehensive rationale of combinational or synergistic effects of Chinese herb-based AgNPs synthesis was investigated with superior physicochemical and biological properties, and their biomedical applications, including antimicrobial and anticancer activity and wound healing properties. AgNPs can damage the cell ultrastructure by triggering apoptosis, which includes the formation of reactive oxygen species (ROS), DNA disintegration, protein inactivation, and the regulation of various signaling pathways. However, the anticancer mechanism of Chinese herbal medicine-based AgNPs is more complicated due to the potential toxicity of AgNPs. Further in-depth studies are required to address Chinese herbs' various bioactive components and AgNPs as a synergistic approach to combat antimicrobial resistance, therapeutic efficiency of drug delivery, and control and prevention of newly emerged diseases.

6.
ACS Appl Mater Interfaces ; 13(28): 32799-32809, 2021 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-34227796

RESUMEN

It has been found that the self-assembly of nonfluorescent peptides can generate fluorescent peptide nanoparticles (f-PNPs) to perform multiple functions, including drug delivery and imaging and tracking therapeutic agents. Both pharmacologically inactive peptides and tumor-targeting peptides have been explored to construct biocompatible f-PNPs; however, the application of this technology in delivering antitumor peptides has never been reported. Herein, the self-assembly of an antitumor dipeptide, carnosine, into fluorescent carnosine nanoparticles (f-Car NPs) in the presence of zinc ions is demonstrated. The generated f-Car NPs exhibit fluorescence in the visible and near-infrared (NIR) ranges for fluorescence tracing in vitro and in vivo. On the other hand, the f-Car NPs minimize the contact between the dipeptide and the serum, which overcomes the dipeptide instability resulted from inefficient antitumor activity. In addition, the preparation of f-Car NPs does not introduce extra carrier materials, so the f-Car NPs exhibit biocompatibility to normal fibroblast cells in vitro and negligible toxicity against major organs in vivo. This study provides a new peptide drug delivery strategy with NIR fluorescence tracing ability.


Asunto(s)
Antineoplásicos/uso terapéutico , Carnosina/uso terapéutico , Colorantes Fluorescentes/uso terapéutico , Nanopartículas del Metal/uso terapéutico , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/química , Antineoplásicos/efectos de la radiación , Antineoplásicos/toxicidad , Carnosina/química , Carnosina/efectos de la radiación , Carnosina/toxicidad , Línea Celular Tumoral , Femenino , Colorantes Fluorescentes/química , Colorantes Fluorescentes/efectos de la radiación , Colorantes Fluorescentes/toxicidad , Fluorometría/métodos , Humanos , Rayos Infrarrojos , Nanopartículas del Metal/química , Nanopartículas del Metal/efectos de la radiación , Nanopartículas del Metal/toxicidad , Ratones Endogámicos BALB C , Nanomedicina Teranóstica/métodos , Zinc/química
7.
Carbohydr Polym ; 202: 246-257, 2018 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-30286998

RESUMEN

Hydrogel with good mechanical and biological properties has great potential and promise for biomedical applications. Here we fabricated a series of novel cytocompatible chitosan (CS) based double-network (DN) and triple-network (TN) hydrogels by physically-chemically crosslinking methods. Natural polysaccharide CS with abundant resources was chosen as the first network due to its good antimicrobial activity, biocompatibility and easy cross-linking reaction. Zwitterionic sulfopropylbetaine (PDMAPS) was chosen as the second network due its good biocompatibility, antimicrobial and antifouling properties. And nonionic poly(2-hydroxyethyl acrylate) (PHEA) was chosen as the final network due to its good biocompatibility, excellent nonfouling and mechanical properties. Cross-section SEM images showed that both CS/PHEA (DN1, the molar ratio of glutaraldehyde to structural unit of CS is 0.2/3.0) and CS/PDMAPS/PHEA (TN1, the molar ratio of glutaraldehyde to structural unit of CS is 0.2/3.0) hydrogels exhibited a smooth and uniformly dispersed porous microstructures with pore size distribution in the range of 20∼100 µm. The largest compressive stress and tensile stress of DN1 hydrogels reached 84.7 MPa and 292 kPa, respectively, and largest compressive stress and tensile stress of TN1 hydrogels could reach 81.9 MPa and 384 kPa, respectively. Moreover, the value of failure strain for TN1 gels reached 1020%. Besides excellent mechanical properties, DN1 and TN1 gels exhibited good antimicrobial, cytocompatible and antifouling properties due to introduction of antimicrobial chitosan, cell anti-adhesive PDMAPS and PHEA. The combination of the excellent mechanical and biological properties of multiple network hydrogels can provide a potential pathway to develop biomedical hydrogels as promising bioapplications in wound dressing and other biomedical applications.


Asunto(s)
Acrilatos/farmacología , Antibacterianos/farmacología , Materiales Biocompatibles/farmacología , Quitosano/farmacología , Reactivos de Enlaces Cruzados/farmacología , Hidrogeles/farmacología , Polímeros/farmacología , Acrilatos/síntesis química , Acrilatos/química , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/química , Adhesión Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Quitosano/química , Reactivos de Enlaces Cruzados/síntesis química , Reactivos de Enlaces Cruzados/química , Escherichia coli/efectos de los fármacos , Hidrogeles/síntesis química , Hidrogeles/química , Ratones , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Células 3T3 NIH , Tamaño de la Partícula , Polímeros/síntesis química , Polímeros/química , Staphylococcus aureus/efectos de los fármacos , Propiedades de Superficie
8.
Nat Commun ; 9(1): 3217, 2018 08 13.
Artículo en Inglés | MEDLINE | ID: mdl-30104564

RESUMEN

Quantum confined materials have been extensively studied for photoluminescent applications. Due to intrinsic limitations of low biocompatibility and challenging modulation, the utilization of conventional inorganic quantum confined photoluminescent materials in bio-imaging and bio-machine interface faces critical restrictions. Here, we present aromatic cyclo-dipeptides that dimerize into quantum dots, which serve as building blocks to further self-assemble into quantum confined supramolecular structures with diverse morphologies and photoluminescence properties. Especially, the emission can be tuned from the visible region to the near-infrared region (420 nm to 820 nm) by modulating the self-assembly process. Moreover, no obvious cytotoxic effect is observed for these nanostructures, and their utilization for in vivo imaging and as phosphors for light-emitting diodes is demonstrated. The data reveal that the morphologies and optical properties of the aromatic cyclo-dipeptide self-assemblies can be tuned, making them potential candidates for supramolecular quantum confined materials providing biocompatible alternatives for broad biomedical and opto-electric applications.


Asunto(s)
Péptidos/química , Puntos Cuánticos/química , Espectroscopía Infrarroja Corta/métodos , Animales , Línea Celular , Dimerización , Fluorescencia , Humanos , Masculino , Ratones Desnudos , Péptidos Cíclicos/química , Puntos Cuánticos/ultraestructura
9.
Nat Commun ; 9(1): 2605, 2018 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-29973582

RESUMEN

Various types of nanoparticles have been proposed for targeted drug delivering, imaging, and tracking of therapeutic agents. However, highly biocompatible nanoparticles with structure-induced fluorescence and capability to conjugate with biomarkers and drugs remain lacking. This research proposes and synthesizes fluorescent nanoparticles (f-PNPs) assembled by cyclic peptides to combine imaging and drug delivering for esophageal cancer (EC). To achieve tumor targeting, f-PNPs are first conjugated with RGD moieties to selectively target EC cells via αvß3 integrin; the nanoparticles are then embedded with epirubicin (EPI). Cell viability assays and analysis of tissue histology reveal that EPI-loaded RGD-f-PNPs (RGD-f-PNPs/EPI) led to significantly reduced cardiotoxicity and improved anti-tumor activity compared to EPI alone. Moreover, the drug delivery to tumor sites and therapeutic responses could be monitored with near-infrared fluorescence using RGD-f-PNPs/EPI. This unique nanoparticle system may lead to potential approaches for bioorganic fluorescence-based delivering, imaging, and drug release tracking.


Asunto(s)
Antibióticos Antineoplásicos/farmacología , Sistemas de Liberación de Medicamentos/métodos , Epirrubicina/farmacología , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/tratamiento farmacológico , Imagen Molecular/métodos , Animales , Antibióticos Antineoplásicos/farmacocinética , Línea Celular Tumoral , Composición de Medicamentos , Monitoreo de Drogas/métodos , Epirrubicina/farmacocinética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Fluorescencia , Humanos , Inyecciones Intraperitoneales , Integrina alfaVbeta3/metabolismo , Masculino , Ratones , Ratones Desnudos , Nanopartículas/administración & dosificación , Nanopartículas/química , Oligopéptidos/química , Oligopéptidos/metabolismo , Péptidos Cíclicos/química , Péptidos Cíclicos/metabolismo , Espectroscopía Infrarroja Corta , Ensayos Antitumor por Modelo de Xenoinjerto
10.
Curr Pharm Des ; 24(21): 2394-2402, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29792137

RESUMEN

BACKGROUND: As the quick development of modern methods and technologies currently, more and more drugs have been invented with a better efficiency. However, the poor water solubility has limited the drugs' pharmaceutical application. METHODS: Tremendous research has been put in the design and development of nanocrystals for pharmaceutical applications over the past few decades. The nanocrystals not only have the chance to solve the poor solubility problem, but also could conquer the bioavailability and even the specific delivery problems. The physical properties of drugs can be changed dramatically due to the change of their size in a nanodimension. Therefore, the nanocrystals have great potential to overcome the challenge to design and development of new drugs for pharmaceutical applications. RESULTS: In this review, we provide an overview of the recent trends in nanocrystals for pharmaceutical applications. CONCLUSION: The current technologies including top-down, bottom-up, and combinative technologies for nanocrystals were fully examined. Most importantly, the emphasis is put on the pharmaceutical applications including their formulation, administration methods, safety, and toxicity. The commercial status, limitations, challenges, and future trends of the nanocrystals for pharmaceutical applications were also discussed.


Asunto(s)
Nanopartículas/química , Preparaciones Farmacéuticas/química , Tecnología Farmacéutica , Humanos
11.
Acta Biomater ; 61: 21-40, 2017 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-28780432

RESUMEN

Postoperative adhesion (POA) is a common complication that often occurs after a variety of surgeries, such as plastic surgery, repair operations of abdominal, pelvic, and tendon, and so forth. Moreover, POA leads to chronic abdominal pain, secondary infertility in women, intestinal obstruction, and other severe complications, which significantly reduce the life quality of patients. In order to prevent the formation of POA, a number of strategies have been developed, among which an emerging method is physical barriers consisting of polymer materials. This review highlights the most commonly used natural and synthetic polymer materials in anti-adhesion physical barriers. The specific features of polymer materials are analyzed and compared, and the possible prospect is also predicted. STATEMENT OF SIGNIFICANCE: Postoperative adhesion (POA) is a serious complication accompanied with various surgeries. Polymer material-based physical barriers have attracted a large amount of attention in POA prevention. The polymer barriers can effectively avoid the formation of fibrous tissues among normal organs by reducing the interconnection of injured tissues. In this review, specific features of the natural and synthetic polymer materials for application in POA prevention were presented, and the possible prospects were predicted. All in all, our work can provide inspiration for researchers to choose proper polymer materials for preclinical and even clinical anti-adhesion studies.


Asunto(s)
Polímeros/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Adherencias Tisulares/prevención & control , Animales , Materiales Biocompatibles/uso terapéutico , Humanos
12.
Sci Adv ; 3(7): e1700669, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28782028

RESUMEN

With the increasing prevalence of Alzheimer's disease (AD), significant efforts have been directed toward developing novel diagnostics and biomarkers that can enhance AD detection and management. AD affects the cognition, behavior, function, and physiology of patients through mechanisms that are still being elucidated. Current AD diagnosis is contingent on evaluating which symptoms and signs a patient does or does not display. Concerns have been raised that AD diagnosis may be affected by how those measurements are analyzed. Unbiased means of diagnosing AD using computational algorithms that integrate multidisciplinary inputs, ranging from nanoscale biomarkers to cognitive assessments, and integrating both biochemical and physical changes may provide solutions to these limitations due to lack of understanding for the dynamic progress of the disease coupled with multiple symptoms in multiscale. We show that nanoscale physical properties of protein aggregates from the cerebral spinal fluid and blood of patients are altered during AD pathogenesis and that these properties can be used as a new class of "physical biomarkers." Using a computational algorithm, developed to integrate these biomarkers and cognitive assessments, we demonstrate an approach to impartially diagnose AD and predict its progression. Real-time diagnostic updates of progression could be made on the basis of the changes in the physical biomarkers and the cognitive assessment scores of patients over time. Additionally, the Nyquist-Shannon sampling theorem was used to determine the minimum number of necessary patient checkups to effectively predict disease progression. This integrated computational approach can generate patient-specific, personalized signatures for AD diagnosis and prognosis.


Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/psicología , Biomarcadores , Cognición , Algoritmos , Biología Computacional , Progresión de la Enfermedad , Módulo de Elasticidad , Humanos , Microscopía de Fuerza Atómica , Modelos Biológicos , Pronóstico
13.
Int J Nanomedicine ; 12: 4789-4803, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28740385

RESUMEN

Although tremendous efforts have been put into the treatment of infectious diseases to prevent epidemics and mortality, it is still one of the major health care issues that have a profound impact on humankind. Therefore, the development of specific, sensitive, accurate, rapid, low-cost, and easy-to-use diagnostic tools is still in urgent demand. Nanodiagnostics, defined as the application of nanotechnology to medical diagnostics, can offer many unique opportunities for more successful and efficient diagnosis and treatment for infectious diseases. In this review, we provide an overview of the nanodiagnostics for infectious diseases from nanoparticle-based, nanodevice-based, and point-of-care test (POCT) platforms. Most importantly, emphasis focused on the recent trends in the nanotechnology-based POCT system. The current state-of-the-art and most promising point-of-care nanodiagnostic technologies, including miniaturized diagnostic magnetic resonance platform, magnetic barcode assay system, cell phone-based polarized light microscopy platform, cell phone-based dongle platform, and paper-based POCT platform, for infectious diseases were fully examined. The limitations, challenges, and future trends of the nanodiagnostics in POCTs for infectious diseases are also discussed.


Asunto(s)
Enfermedades Transmisibles/diagnóstico , Sistemas de Atención de Punto/tendencias , Humanos , Magnetismo , Nanomedicina/métodos , Nanomedicina/tendencias , Nanopartículas
14.
Proc Natl Acad Sci U S A ; 113(23): E3193-202, 2016 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-27217558

RESUMEN

Over 130 y have passed since Charles Darwin first discovered that the adventitious roots of English ivy (Hedera helix) exude a yellowish mucilage that promotes the capacity of this plant to climb vertical surfaces. Unfortunately, little progress has been made in elucidating the adhesion mechanisms underlying this high-strength adhesive. In the previous studies, spherical nanoparticles were observed in the viscous exudate. Here we show that these nanoparticles are predominantly composed of arabinogalactan proteins (AGPs), a superfamily of hydroxyproline-rich glycoproteins present in the extracellular spaces of plant cells. The spheroidal shape of the AGP-rich ivy nanoparticles results in a low viscosity of the ivy adhesive, and thus a favorable wetting behavior on the surface of substrates. Meanwhile, calcium-driven electrostatic interactions among carboxyl groups of the AGPs and the pectic acids give rise to the cross-linking of the exuded adhesive substances, favor subsequent curing (hardening) via formation of an adhesive film, and eventually promote the generation of mechanical interlocking between the adventitious roots of English ivy and the surface of substrates. Inspired by these molecular events, a reconstructed ivy-mimetic adhesive composite was developed by integrating purified AGP-rich ivy nanoparticles with pectic polysaccharides and calcium ions. Information gained from the subsequent tensile tests, in turn, substantiated the proposed adhesion mechanisms underlying the ivy-derived adhesive. Given that AGPs and pectic polysaccharides are also observed in bioadhesives exuded by other climbing plants, the adhesion mechanisms revealed by English ivy may forward the progress toward understanding the general principles underlying diverse botanic adhesives.


Asunto(s)
Adhesivos/química , Hedera/química , Mucoproteínas/química , Secuencia de Aminoácidos , Secuencia de Bases , Calcio/química , Reactivos de Enlaces Cruzados , ADN de Plantas/genética , Hedera/genética , Microscopía de Fuerza Atómica , Modelos Moleculares , Estructura Molecular , Mucoproteínas/genética , Mucoproteínas/ultraestructura , Nanosferas/química , Nanosferas/ultraestructura , Pectinas/química , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/ultraestructura , Humectabilidad
15.
Nat Nanotechnol ; 11(4): 388-94, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26751169

RESUMEN

Peptide nanostructures are biodegradable and are suitable for many biomedical applications. However, to be useful imaging probes, the limited intrinsic optical properties of peptides must be overcome. Here we show the formation of tryptophan-phenylalanine dipeptide nanoparticles (DNPs) that can shift the peptide's intrinsic fluorescent signal from the ultraviolet to the visible range. The visible emission signal allows the DNPs to act as imaging and sensing probes. The peptide design is inspired by the red shift seen in the yellow fluorescent protein that results from π-π stacking and by the enhanced fluorescence intensity seen in the green fluorescent protein mutant, BFPms1, which results from the structure rigidification by Zn(II). We show that DNPs are photostable, biocompatible and have a narrow emission bandwidth and visible fluorescence properties. DNPs functionalized with the MUC1 aptamer and doxorubicin can target cancer cells and can be used to image and monitor drug release in real time.


Asunto(s)
Dipéptidos/farmacocinética , Colorantes Fluorescentes/farmacocinética , Nanopartículas/química , Neoplasias/patología , Imagen Óptica/métodos , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Línea Celular Tumoral , Dipéptidos/química , Doxorrubicina/química , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberación de Fármacos , Colorantes Fluorescentes/química , Humanos , Ratones , Neoplasias/metabolismo
16.
ACS Appl Mater Interfaces ; 8(3): 2423-34, 2016 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-26731614

RESUMEN

The potential to harness the unique physical, chemical, and biological properties of the sundew (Drosera) plant's adhesive hydrogels has long intrigued researchers searching for novel wound-healing applications. However, the ability to collect sufficient quantities of the sundew plant's adhesive hydrogels is problematic and has eclipsed their therapeutic promise. Inspired by these natural hydrogels, we asked if sundew-inspired adhesive hydrogels could overcome the drawbacks associated with natural sundew hydrogels and be used in combination with stem-cell-based therapy to enhance wound-healing therapeutics. Using a bioinspired approach, we synthesized adhesive hydrogels comprised of sodium alginate, gum arabic, and calcium ions to mimic the properties of the natural sundew-derived adhesive hydrogels. We then characterized and showed that these sundew-inspired hydrogels promote wound healing through their superior adhesive strength, nanostructure, and resistance to shearing when compared to other hydrogels in vitro. In vivo, sundew-inspired hydrogels promoted a "suturing" effect to wound sites, which was demonstrated by enhanced wound closure following topical application of the hydrogels. In combination with mouse adipose-derived stem cells (ADSCs) and compared to other therapeutic biomaterials, the sundew-inspired hydrogels demonstrated superior wound-healing capabilities. Collectively, our studies show that sundew-inspired hydrogels contain ideal properties that promote wound healing and suggest that sundew-inspired-ADSCs combination therapy is an efficacious approach for treating wounds without eliciting noticeable toxicity or inflammation.


Asunto(s)
Adhesivos/farmacología , Tejido Adiposo/citología , Drosera/química , Hidrogeles/farmacología , Trasplante de Células Madre , Células Madre/citología , Cicatrización de Heridas/efectos de los fármacos , Animales , Línea Celular , Separación Celular , Supervivencia Celular/efectos de los fármacos , Femenino , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Humanos , Ratones Endogámicos C57BL , Células Madre/efectos de los fármacos
17.
J Nanosci Nanotechnol ; 15(1): 93-9, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26328309

RESUMEN

An experimental investigation on the effects of in vitro hydrolytic and enzymatic degradation on mechanical properties of polyglactin 910 monofilament sutures was performed by conducting nanoindentation studies using an atomic force microscope (AFM). For hydrolytic degradation, the sutures were incubated in phosphate buffered saline (PBS) solution at three different pH conditions, 5, 7.4, and 10. For enzymatic degradation, esterase was employed at pH condition of 7.4. The property of the sutures changed with time at different conditions were investigated by nanoindentation, tensile test experiments, image analysis using both of scanning electron microscopy (SEM) and AFM, and also Fourier transform infrared spectroscopy (FTIR). The effects of degradation on gradation of Young's modulus values across the cross section of the sutures were studied by doing progressive nanoindentation from center to surface. FTIR studies revealed the formation of new hydroxyl bonds due to both hydrolytic and enzymatic degradations. Nanoindentation results indicated that the degradation does not cause a gradient of Young's modulus of the polyglactin 910 monofilament sutures across the cross section from center to surface at different degradation times for both hydrolytic and enzymatic degradations. However, in general, the Young's modulus of all samples was decreased over 4 weeks of degradation. The microscopic evaluation of the samples also showed both qualitative changes in surface morphology and quantitative changes in surface roughness on the surface of degraded sutures. This study provided a deep understanding of the polyglactin sutures subjected to in vitro hydrolytic and enzymatic degradation, and also opened a new avenue to study the biomaterials at nano-scale.


Asunto(s)
Materiales Biocompatibles/química , Nanoestructuras/química , Poliglactina 910/química , Suturas , Módulo de Elasticidad , Hidrólisis , Ensayo de Materiales
18.
Acta Biomater ; 25: 268-83, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26219859

RESUMEN

Arabinoglactan protein (AGP)-rich nanoparticles obtained from the sticky exudates of Hedera helix (English ivy), have shown promising potential to be used in nanomedicine owing to their excellent aqueous solubility, low intrinsic viscosity, biocompatibility, and biodegradability. In this study, the feasibilities of utilizing ivy nanoparticles (INPs) as nano-carriers for delivering chemotherapeutic drugs in cancer therapy and as nano-fillers to develop novel scaffolds for tissue engineering in regenerative medicine are evaluated. Via electrostatic and hydrophobic interactions, pH-responsive nanoconjugates are formed between the INPs and the doxorubicin (DOX) with an entrapment ratio of 77.9±3.9%. While the INPs show minimal cytotoxicity, the formed INP-DOX conjugates exhibit substantially stronger cytotoxic activity than free DOX against multiple cancer cell lines, suggesting a synergistic effect is established upon conjugation. The anti-cancer effects of the INP-DOX conjugates are further evaluated via in vivo xenograft assays by subcutaneously implanting DOX resistant cell line, SW620/Ad-300, into nude mice. The tumor volumes in mice treated with the INP-DOX conjugates are significantly less than those of the mice treated with free DOX. In addition, the INPs are further exploited as nano-fillers to develop fibrous scaffolds with collagen, via mimicking the porous matrix where the INPs are embedded under natural condition. Enhanced adhesion of smooth muscle cells (SMCs) and accelerated proliferation of mouse aortic SMCs are observed in this newly constructed scaffold. Overall, the results obtained from the present study suggest great potential of the INPs to be used as biocompatible nanomaterials in nanomedicine. The AGP-rich INP renders a glycoprotein architecture that is amenable for modification according to the functional designs, capable of being developed as versatile nanomaterials for extensive biomedical applications. STATEMENT OF SIGNIFICANCE: Naturally occurring organic nanomaterials have drawn increasing interest for their potential biomedical applications in recent years. In this study, a new type of naturally occurring nanoparticles obtained from the sticky exudates on the adventitious roots of English ivy (H. helix), was explored for its potential biomedical application. In particular, the feasibilities of utilizing ivy nanoparticles (INPs) as nano-carriers for delivering chemotherapeutic drugs in cancer therapy and as nano-fillers to develop novel scaffolds for tissue engineering in regenerative medicine were evaluated both in vitro and in vivo. Overall, the results obtained from the present study suggest the great potential of the INPs to be used as biocompatible nanomaterials in nanomedicine. This study may open a totally new frontier for exploring the biomedical application of naturally occurring nanomaterials.


Asunto(s)
Materiales Biocompatibles/farmacología , Hedera/química , Nanopartículas/química , Animales , Antineoplásicos/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Doxorrubicina/farmacología , Endocitosis/efectos de los fármacos , Fluoresceína-5-Isotiocianato/química , Humanos , Concentración de Iones de Hidrógeno , Espacio Intracelular/química , Masculino , Ratones , Ratones Desnudos , Nanopartículas/ultraestructura , Concentración Osmolar , Raíces de Plantas/química , Electricidad Estática
19.
J R Soc Interface ; 12(107)2015 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-25948615

RESUMEN

Bioadhesives have drawn increasing interest in recent years, owing to their eco-friendly, biocompatible and biodegradable nature. As a typical bioadhesive, sticky exudate observed on the stalked glands of sundew plants aids in the capture of insects and this viscoelastic adhesive has triggered extensive interests in revealing the implied adhesion mechanisms. Despite the significant progress that has been made, the structural traits of the sundew adhesive, especially the morphological characteristics in nanoscale, which may give rise to the viscous and elastic properties of this mucilage, remain unclear. Here, we show that the sundew adhesive is a naturally occurring hydrogel, consisting of nano-network architectures assembled with polysaccharides. The assembly process of the polysaccharides in this hydrogel is proposed to be driven by electrostatic interactions mediated with divalent cations. Negatively charged nanoparticles, with an average diameter of 231.9 ± 14.8 nm, are also obtained from this hydrogel and these nanoparticles are presumed to exert vital roles in the assembly of the nano-networks. Further characterization via atomic force microscopy indicates that the stretching deformation of the sundew adhesive is associated with the flexibility of its fibrous architectures. It is also observed that the adhesion strength of the sundew adhesive is susceptible to low temperatures. Both elasticity and adhesion strength of the sundew adhesive reduce in response to lowering the ambient temperature. The feasibility of applying sundew adhesive for tissue engineering is subsequently explored in this study. Results show that the fibrous scaffolds obtained from sundew adhesive are capable of increasing the adhesion of multiple types of cells, including fibroblast cells and smooth muscle cells, a property that results from the enhanced adsorption of serum proteins. In addition, in light of the weak cytotoxic activity exhibited by these scaffolds towards a variety of mammal cells, evidence is sufficient to propose that sundew adhesive is a promising nanomaterial worth further exploitation in the field of tissue engineering.


Asunto(s)
Adhesivos/química , Drosera/química , Hidrogeles/química , Ensayo de Materiales , Polisacáridos/química , Animales , Adhesión Celular , Drosera/metabolismo , Humanos , Ratones , Células 3T3 NIH
20.
Soft Matter ; 11(19): 3822-32, 2015 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-25858105

RESUMEN

While tremendous efforts have been made in investigating scalable approaches for fabricating nanoparticles, less progress has been made in scalable synthesis of cyclic peptide nanoparticles and nanotubes, despite their great potential for broader biomedical applications. In this paper, tunable synthesis of self-assembled cyclic peptide nanotubes and nanoparticles using three different methods, phase equilibrium, pH-driven, and pH-sensitive methods, were proposed and investigated. The goal is scalable nanomanufacturing of cyclic peptide nanoparticles and nanotubes with different sizes in large quality by controlling multiple process parameters. Cyclo-(L-Gln-D-Ala-L-Glu-D-Ala-)2 was applied to illustrate the proposed ideas. In the study, mass spectrometry and high performance liquid chromatography were employed to verify the chemical structures and purity of the cyclic peptides. Morphology and size of the synthesized nanomaterials were characterized using atomic force microscopy and dynamic light scattering. The dimensions of the self-assembled nanostructures were found to be strongly influenced by the cyclic peptide concentration, side chain modification, pH values, reaction time, stirring intensity, and sonication time. This paper proposed an overall strategy to integrate all the parameters to achieve optimal synthesis outputs. Mechanisms of the self-assembly of the cyclic peptide nanotubes and nanoparticles under variable conditions and tunable parameters were discussed. This study contributes to scalable nanomanufacturing of cyclic peptide based self-assembled nanoparticles and nanotubes for broader biomedical applications.


Asunto(s)
Nanopartículas/química , Nanotecnología/métodos , Nanotubos de Péptidos/química , Secuencia de Aminoácidos , Técnicas de Química Sintética , Concentración de Iones de Hidrógeno , Cinética , Sonicación
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