RESUMEN
The higher rate of soft tissue impairment due to lumpectomy or other trauma greatly requires the restoration of the irreversibly lost subcutaneous adipose tissues. The nanofibers fabricated by conventional electrospinning provide only a superficial porous structure due to its sheet like 2D structure and thereby hinder the cell infiltration and differentiation throughout the scaffolds. Thus we developed a novel electrospun 3D membrane using the zwitterionic poly (carboxybetaine-co-methyl methacrylate) co-polymer (CMMA) through electrostatic repulsion based electrospinning for soft tissue engineering. The inherent charges in the CMMA will aid the nanofiber to directly transform into a semiconductor and thereby transfer the immense static electricity from the grounded collector and will impart greater fluffiness to the scaffolds. The results suggest that the fabricated 3D nanofiber (CMMA 3NF) scaffolds possess nanofibers with larger inter connected pores and less dense structure compared to the conventional 2D scaffolds. The CMMA 3NF exhibits significant cues of soft tissue engineering such as enhanced biocompatibility as well as the faster regeneration of cells. Moreover the fabricated 3D scaffolds greatly assist the cells to develop into its stereoscopic topographies with an enhanced adipogenic property.
Asunto(s)
Adipocitos/citología , Materiales Biomiméticos/síntesis química , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Células 3T3-L1 , Adipogénesis , Animales , Materiales Biomiméticos/química , Diferenciación Celular , Matriz Extracelular , Ratones , Polímeros/química , PorosidadRESUMEN
The study describes the design and synthesis of an implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release. This device is achieved using a two-component smart nanofiber matrix from monodisperse iron oxide nanoparticles (IONPs) as well as bortezomib (BTZ), a chemotherapeutic drug. The IONP-incorporated nanofiber matrix was developed by electrospinning a biocompatible and bioresorbable polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by exploiting mussel-inspired surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the borate-containing BTZ anticancer drug through a catechol metal binding in a pH-sensitive manner. Thus, an implantable smart magnetic nanofiber device can be exploited to both apply hyperthermia with an alternating magnetic field (AMF) and to achieve cancer cell-specific drug release to enable synergistic cancer therapy. These results confirm that the BTZ-loaded mussel-inspired magnetic nanofiber matrix (BTZ-MMNF) is highly beneficial not only due to the higher therapeutic efficacy and low toxicity towards normal cells but also, as a result of the availability of magnetic nanoparticles for repeated hyperthermia application and tumor-triggered controlled drug release. STATEMENT OF SIGNIFICANCE: The current work report on the design and development of a smart nanoplatform responsive to a magnetic field to administer both hyperthermia and pH-dependent anticancer drug release for the synergistic anticancer treatment. The iron oxide nanoparticles (IONPs) incorporated nanofiber matrix was developed by electrospinning a biocompatible polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the boratecontaining anticancer drug bortezomib through a catechol metal binding in a pH-sensitive manner. This implantable magnetic nanofiber device can be exploited to apply hyperthermia with an alternating magnetic field and to achieve cancer cell-specific drug release to enable synergistic cancer therapy, which results in an improvement in both quality of life and patient compliance.
Asunto(s)
Sistemas de Liberación de Medicamentos , Endoscopía/métodos , Hipertermia Inducida/métodos , Nanofibras/química , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Materiales Biocompatibles/química , Bivalvos , Bortezomib/administración & dosificación , Bortezomib/química , Catecoles/química , Línea Celular Tumoral , Dopamina/química , Liberación de Fármacos , Endoscopios , Compuestos Férricos/química , Concentración de Iones de Hidrógeno , Ácido Láctico/química , Magnetismo , Nanopartículas de Magnetita/química , Ratones , Células 3T3 NIH , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , TermogravimetríaRESUMEN
We report the versatile design of a smart nanoplatform for thermo-chemotherapy treatment of cancer. For the first time in the literature, our design takes advantage of the outstanding properties of mussel-inspired multiple catecholic groups - presenting a unique copolymer poly(2-hydroxyethyl methacrylate-co-dopamine methacrylamide) p(HEMA-co-DMA) to surface functionalize the superparamagnetic iron oxide nanoparticles as well as to conjugate borate containing anticancer drug bortezomib (BTZ) in a pH-dependent manner for the synergistic anticancer treatment. The unique multiple anchoring groups can be used to substantially improve the affinity of the ligands to the surfaces of the nanoparticles to form ultrastable iron oxide nanoparticles with control over their hydrodynamic diameter and interfacial chemistry. Thus the BTZ-incorporated-bio-inspired-smart magnetic nanoplatform will act as a hyperthermic agent that delivers heat when an alternating magnetic field is applied while the BTZ-bound catechol moieties act as chemotherapeutic agents in a cancer environment by providing pH-dependent drug release for the synergistic thermo-chemotherapy application. The anticancer efficacy of these bio-inspired multifunctional smart magnetic nanoparticles was tested both in vitro and in vivo and found that these unique magnetic nanoplatforms can be established to endow for the next generation of nanomedicine for efficient and safe cancer therapy.
Asunto(s)
Antineoplásicos , Bortezomib , Sistemas de Liberación de Medicamentos/métodos , Compuestos Férricos , Hipertermia Inducida/métodos , Campos Magnéticos , Nanopartículas/química , Neoplasias/terapia , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Bortezomib/química , Bortezomib/farmacología , Línea Celular Tumoral , Compuestos Férricos/química , Compuestos Férricos/farmacología , Metacrilatos/química , Metacrilatos/farmacología , Ratones , Células 3T3 NIHRESUMEN
Recently, superparamagnetic iron oxide nanoparticles (SPIONs) have been prepared for magnetic resonance (MR) imaging and hyperthermia therapy. Here, we have developed hyaluronic acid (HA) coated SPIONs primarily for use in a hyperthermia application with an MR diagnostic feature with hydrodynamic size measurement of 176nm for HA-PEG10-SPIONs and 149nm for HA-SPIONs. HA-coated SPIONs (HA-SPIONs) were prepared to target CD44-expressed cancer where the carrier was conjugated to PEG for analyzing longer circulation in blood as well as for biocompatibility (HA-PEG10 SPIONs). Characterization was conducted with TEM (shape), DLS (size), ELS (surface charge), TGA (content of polymer) and MRI (T2-relaxation time). The heating ability of both the HA-SPIONs and HA-PEG10-SPIONs was studied by AMF and SAR calculation. Cellular level tests were conducted using SCC7 and NIH3T3 cell lines to confirm cell viability and cell specific uptake. HA-SPIONs and HA-PEG10-SPIONs were injected to xenograft mice bearing the SCC7 cell line for MRI cancer diagnosis. We found that HA-SPION-injected mice tumors showed nearly 40% MR T2 contrast compared to the 20% MR T2 contrast of the HA-PEG10-SPION group over a 3h time period. Finally, in vitro hyperthermia studies were conducted in the SCC7 cell line that showed less than 40% cell viability for both HA-SPIONs and HA-PEG10-SPIONs in AMF treated cells. In conclusion, HA-SPIONs were targeted specifically to the CD44, and the hyperthermia effect of HA-SPIONs and HA-PEG10-SPIONs was found to be significant for future studies.
Asunto(s)
Dextranos/química , Ácido Hialurónico/química , Hipertermia Inducida , Nanopartículas de Magnetita/química , Neoplasias/diagnóstico , Neoplasias/terapia , Animales , Muerte Celular , Línea Celular Tumoral , Dextranos/ultraestructura , Endocitosis , Humanos , Imagen por Resonancia Magnética , Nanopartículas de Magnetita/ultraestructura , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Células 3T3 NIH , Coloración y Etiquetado , Temperatura , Factores de TiempoRESUMEN
Post-menopausal wound care management is a substantial burden on health services, since there are an increased number of elderly populations linked with age-related delayed wound healing. The controlled estrogen replacement can accelerate healing of acute cutaneous wounds, linked to its potent anti-inflammatory activity. The electrospinning technique can be used to introduce the desired therapeutic agents to the nanofiber matrix. So here we introduce a new material for wound tissue dressing, in which a polyurethane-dextran composite nanofibrous wound dressing material loaded with ß-estradiol was obtained through electrospinning. Dextran can promote neovascularization and skin regeneration in chronic wounds. This study involves the characterization of these nanofibers and analysis of cell growth and proliferation to determine the efficiency of tissue regeneration on these biocomposite polymer nanofibrous scaffolds and to study the possibility of using it as a potential wound dressing material in the in vivo models.