RESUMO
Loading of chemotherapeutic agents into nanoparticles has been demonstrated to be an effective strategy for cancer therapy. However, simultaneous delivery of different functional drugs to tumor sites for chemotherapy still remains challenging. In this study, nanogels formed by an engineered coiled-coil polypeptide PC10A were designed and prepared as a carrier for co-delivery of paclitaxel (PTX) and doxorubicin (DOX) through ultrasonic treatment and electrostatic adsorption. The drug loading content and encapsulation efficiency of PTX and DOX in the PC10A/PTX/DOX nanogels were 5.98 wt%, 70 wt%, and 8.55 wt%, 83 wt%, respectively. Because the polypeptide PC10A was non-toxic and biodegradable, the PC10A/PTX/DOX nanogels exhibited good biocompatibility. Thein vitroandin vivoantitumor experiments showed that the PC10A/PTX/DOX nanogels possessed obviously synergistic therapy effect of tumors and lower side effects compared with free PTX/DOX. Therefore, the PC10A/PTX/DOX nanogels are promising to provide a new strategy for combination therapy of different functional drugs.
Assuntos
Antineoplásicos , Doxorrubicina , Portadores de Fármacos , Nanogéis/química , Paclitaxel , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Quimioterapia Combinada , Feminino , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Paclitaxel/química , Paclitaxel/farmacocinética , Paclitaxel/farmacologia , Peptídeos/químicaRESUMO
A high quantum yield (4.3%) hybrid nanogel system based on engineered polypeptides and Ag2S quantum dots has been developed as a multifunctional diagnostic and therapeutic agent for targeted second near-infrared fluorescence, photoacoustic imaging, and photothermal therapy.
Assuntos
Géis/química , Nanoestruturas/química , Imagem Óptica , Peptídeos/química , Técnicas Fotoacústicas , Engenharia de Proteínas , Pontos Quânticos , Compostos de Prata/química , Fluorescência , Células HeLa , Humanos , Células MCF-7 , Tamanho da Partícula , Fototerapia , Teoria Quântica , Propriedades de SuperfícieRESUMO
A new hybrid nanogel system using polypetide-engineered coated gold nanorods has been developed for targeted drug delivery and tumor chemo-photothermal therapy. A triblock engineered polypeptide PC10A(RGD) was immobilized on the surface of gold nanorods by the electrostatic adsorption. The immobilized PC10A(RGD) formed hydrogel by self-assembly to load doxorubicin for chemotherapy. Coating polypeptide-engineering hydrogel on gold nanorods enhanced the stability in high-salt media and significantly reduced the cytotoxicity. An arginine-glycine-aspartic acid motif was introduced into the polypeptide on the surface of hybrid nanogels to promote cellular uptake through receptor-mediated endocytosis in αvß3 overexpressing HeLa cells. In addition, compared with single chemotherapy and near-infrared photothermal therapy, the combination therapy has a synergistic effect on the cancer cells. Thus, the chemo-photothermal therapy based on polypeptide-engineered hydrogel coated gold nanorods and doxorubicin is expected to have great potential impact on cancer therapy.
RESUMO
A facile method for in situ fabrication of three-dimensional gold nanoparticle micropatterns in a cell-resistant polyethylene glycol hydrogel has been developed by combining photochemical synthesis of gold nanoparticles with photolithography technology. The gold nanoparticle micropatterns were further bio-modified with cell integrated polypeptide NcysBRGD based on a gold-thiol bond to improve cell behaviors. Primary cell tests showed that NcysBRGD can enhance cell adhesion very well on the surface of gold nanoparticle micropatterns.
Assuntos
Ouro/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Nanopartículas Metálicas/química , Peptídeos/química , Sequência de Aminoácidos , Materiais Biocompatíveis/química , Adesão Celular , Desenho de Equipamento , Células HeLa , Humanos , Nanopartículas Metálicas/ultraestrutura , Microtecnologia , Dados de Sequência Molecular , Compostos de Sulfidrila/química , Análise Serial de Tecidos/instrumentaçãoRESUMO
Quantum dot (QD)-polypeptide probes have been developed through the specific metal-affinity interaction between polypeptides appended with N-terminal polyhistidine sequences and CdSe/ZnS core-shell QDs. The size and charge of a QD-polypeptide can be tuned by using different coiled-coil polypeptides. Compared to glutathione-capped QDs (QD-GSH), QD-polypeptide probes showed an approximately two- to three-fold luminescence increase, and the luminescence increase was not obviously related to the charge of the polypeptide. QD-polypeptide probes with different charge have a great effect on nonspecific cellular uptake. QD-polypeptide probes with negative charge exhibited lower nonspecific cellular uptake in comparison to the QD-GSH, while positively charged QD-polypeptide probes presented higher cellular uptake than the QD-GSH. A targeted QD-ARGD probe can obviously increase targeted cellular uptake in α v ß 3 overexpressing HeLa cells compared to QD-A. In addition, QD-polypeptide probes showed lower in vitro cytotoxicity compared to the original QDs. These results demonstrate that these QD-polypeptide probes with high specific cellular uptake, high fluorescence intensity and low background noise are expected to have great potential applications in targeted cell imaging.
Assuntos
Técnicas Citológicas/métodos , Imagem Óptica/métodos , Peptídeos/química , Pontos Quânticos/química , Células HeLa , Humanos , Células MCF-7RESUMO
A near-infrared light-controlled hybrid platform with polypeptide-engineered functionalized gold nanorods has been designed for reversible presentation of the immobilized ligands to cell surface receptors on the engineered materials.