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991.
Vaginal cancer is a rare disease of the lower genital tract. We present the case of a 54-year-old woman with occult vaginal cancer after hysterectomy for cervical intraepithelial neoplasia (CIN) III. Despite persistently negative cytology and colposcopy results, a lesion was finally detected by vagino-recto-abdominal examination and she underwent radical parametrectomy and lymph node dissection. We consider the possibility that transabdominal suturing of the vaginal cuff after hysterectomy may reduce the ability to detect subsequent vaginal lesions, and discuss the benefits of a vaginal suture approach. We recommend that suturing the vagina apex transvaginally instead of transabdominally would benefit patients during follow-up. 相似文献
992.
Başak Şahin Jeremy Fife Manoj B. Parmar Juliana Valencia-Serna Hilal Gul-Uludağ Xiaoyan Jiang Michael Weinfeld Afsaneh Lavasanifar Hasan Uludağ 《Biomaterials》2014
Cutaneous T-cell lymphomas (CTCLs) arise from specific molecular aberrations that lead to uncontrolled cell proliferation. RNA interference (RNAi) with short interfering RNAs (siRNAs) is a feasible approach to interrupt aberrant signal processing in CTCL cells, but functional biomaterial carriers are needed to effectively deliver siRNAs intracellularly. Towards this goal, we explored the utility of lipid-substituted polyethylenimines (PEI) carriers in a cell model of CTCL. Using caprylic and linoleic acid substituted 2 kDa PEI (PEI-CA and PEI-LA, respectively), we showed effective delivery of siRNA to T-lymphocyte Hut78 and Jurkat cells, but silencing of a model protein (Green Fluorescent Protein, GFP) was possible only in the Hut78 cells. To enhance siRNA delivery to Hut78 cells, a high siRNA: carrier ratio used to assemble the complexes and centrifugation of cells in the presence of complexes were found effective. The toxicities of PEI-CA and PEI-LA were significantly lower than other commercial carriers, 25 kDa PEI and Lipofectamine® RNAiMAX. This might have contributed to reduced siRNA delivery efficiency of the latter carriers. Screening several endogenous targets led us to identify phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and cyclin-dependent kinase 18 (CDK18) as viable targets to induce siRNA-mediated cell growth inhibition. The results of this study identified promising polymeric carriers and molecular targets that could control proliferation of CTCL cells based on RNAi therapy. 相似文献
993.
Dongmei Yang Yunlu Dai Jianhua Liu Ying Zhou Yinyin Chen Chunxia Li Ping'an Ma Jun Lin 《Biomaterials》2014
A new type of drug-delivery system (DDS) was constructed, in which the anti-cancer drug doxorubicin (DOX) was conjugated to the ultra-small sized (sub-10 nm) BaGdF5:Yb3+/Tm3+ based upconversion nanoparticles (UCNPs). This multifunctional DDS simultaneously possesses drug delivery and optical/magnetic/X-ray computed tomography imaging capabilities. The DOX can be selectively released by cleavage of hydrazone bonds in acidic environment, which shows a pH-triggered drug release behavior. The MTT assay shows these DOX-conjugated UCNPs exhibit obvious cytotoxic effect on HeLa cells. Moreover, to improve the upconversion luminescence intensity, core–shell structured UCNPs were constructed. The in vitro upconversion luminescence images of these UCNPs uptaken by HeLa cells show bright emission with high contrast. In addition, these UCNPs were further explored for T1-weighted magnetic resonance (MR) and X-ray computed tomography (CT) imaging in vitro. Long-term in vivo toxicity studies indicated that mice intravenously injected with 10 mg/kg of UCNPs survived for 40 days without any apparent adverse effects to their health. The results indicate that this multifunctional drug-delivery system with optimized size, excellent optical/MR/CT trimodal imaging capabilities, and pH-triggered drug release property is expected to be a promising platform for simultaneous cancer therapy and bioimaging. 相似文献
994.
Design of an efficient gene vector based on dendrimer remains a great challenge due to the presence of multiple barriers in gene delivery. Single-functionalization on dendrimer cannot overcome all the barriers. In this study, we synthesized a list of single-, dual- and triple-functionalized dendrimers with arginine, phenylalanine and histidine for gene delivery using a one-pot approach. The three amino acids play different roles in gene delivery: arginine is essential in formation of stable complexes, phenylalanine improves cellular uptake efficacy, and histidine increases pH-buffering capacity and minimizes cytotoxicity of the cationic dendrimer. A combination of these amino acids on dendrimer generates a synergistic effect in gene delivery. The dual- and triple-functionalized dendrimers show minimal cytotoxicity on the transfected NIH 3T3 cells. Using this combination strategy, we can obtain triple-functionalized dendrimers with comparable transfection efficacy to several commercial transfection reagents. Such a combination strategy should be applicable to the design of efficient and biocompatible gene vectors for gene delivery. 相似文献
995.
Resistance to single or multiple chemotherapeutic drugs is a major complication in clinical oncology and is one of the most common treatment limitations in patients with reoccurring cancers. Nanoparticle (NP)-based drug delivery systems (DDS's) have been shown to overcome drug resistance in cancer cells mainly by avoiding the activation of efflux pumps in these cells. We demonstrate in this work that polyester-based hyperbranched dendritic-linear (HBDL)-based NPs carrying doxorubicin (Dox) can effectively overcome microsomal glutathione transferase 1 (MGST1)-mediated drug resistance in breast cancer cells. Our DDS was much more effective at considerably lower intracellular Dox concentrations (IC50 6.3 μm vs. 36.3 μm) and achieved significantly greater reductions in viability and induced higher degrees of apoptosis (31% vs. 14%) compared to the free drug in the resistant cells. Dox-loaded HBDL NPs were found to translocate across the membranes of resistant cells via active endocytic pathways and to be transported to lysosomes, mitochondria, and the endoplasmic reticulum. A significantly lower amount of Dox accumulated in these cytoplasmic compartments in resistant cells treated with free Dox. Moreover, we found that Dox-HBDL significantly decreased the expression of MGST1 and enhanced mitochondria-mediated apoptotic cell death compared to free Dox. Dox-HBDL also markedly activated the JNK pathway that contributes to the apoptosis of drug-resistant cells. These results suggest that HBDL NPs can modulate subcellular drug distribution by specific endocytic and trafficking pathways and that this results in drug delivery that alters enzyme levels and cellular signaling pathways and, most importantly, increases the induction of apoptosis. Our findings suggest that by exploiting the cell transport machinery we can optimize the polymeric vehicles for controlled drug release to overcome drug resistance combat drug resistance with much higher efficacy. 相似文献
996.
997.
Francisca Araújo Neha Shrestha Mohammed-Ali Shahbazi Pedro Fonte Ermei M. Mäkilä Jarno J. Salonen Jouni T. Hirvonen Pedro L. Granja Hélder A. Santos Bruno Sarmento 《Biomaterials》2014
Glucagon like peptide-1 (GLP-1) is an incretin hormone that is in the pipeline for type 2 diabetes mellitus (T2DM) therapy. However, oral administration of GLP-1 is hindered by the harsh conditions of the gastrointestinal tract and poor bioavailability. In this study, three nanosystems composed by three different biomaterials (poly(lactide-co-glycolide) polymer (PLGA), Witepsol E85 lipid (solid lipid nanoparticles, SLN) and porous silicon (PSi) were developed and loaded with GLP-1 to study their permeability in vitro. All the nanoparticles presented a size of approximately 200 nm. The nanoparticles' interaction with the mucus and the intestinal cells were enhanced after coating with chitosan (CS). PSi nanosystems presented the best association efficiency (AE) and loading degree (LD), even though a high AE was also observed for PLGA nanoparticles and SLN. Among all the nanosystems, PLGA and PSi were the only nanoparticles able to sustain the release of GLP-1 in biological fluids when coated with CS. This characteristic was also maintained when the nanosystems were in contact with the intestinal Caco-2 and HT29-MTX cell monolayers. The CS-coated PSi nanoparticles showed the highest GLP-1 permeation across the intestinal in vitro models. In conclusion, PLGA + CS and PSi + CS are promising nanocarriers for the oral delivery of GLP-1. 相似文献
998.
Thavasyappan Thambi V.G. Deepagan Hong Yeol Yoon Hwa Seung Han Seol-Hee Kim Soyoung Son Dong-Gyu Jo Cheol-Hee Ahn Yung Doug Suh Kwangmeyung Kim Ick Chan Kwon Doo Sung Lee Jae Hyung Park 《Biomaterials》2014
Hypoxia is a condition found in various intractable diseases. Here, we report self-assembled nanoparticles which can selectively release the hydrophobic agents under hypoxic conditions. For the preparation of hypoxia-responsive nanoparticles (HR-NPs), a hydrophobically modified 2-nitroimidazole derivative was conjugated to the backbone of the carboxymethyl dextran (CM-Dex). Doxorubicin (DOX), a model drug, was effectively encapsulated into the HR-NPs. The HR-NPs released DOX in a sustained manner under the normoxic condition (physiological condition), whereas the drug release rate remarkably increased under the hypoxic condition. From in vitro cytotoxicity tests, it was found the DOX-loaded HR-NPs showed higher toxicity to hypoxic cells than to normoxic cells. Microscopic observation showed that the HR-NPs could effectively deliver DOX into SCC7 cells under hypoxic conditions. In vivo biodistribution study demonstrated that HR-NPs were selectively accumulated at the hypoxic tumor tissues. As consequence, drug-loaded HR-NPs exhibited high anti-tumor activity in vivo. Overall, the HR-NPs might have a potential as nanocarriers for drug delivery to treat hypoxia-associated diseases. 相似文献
999.
Huixia Wu Haili Shi Hao Zhang Xue Wang Yan Yang Chao Yu Caiqin Hao Jing Du He Hu Shiping Yang 《Biomaterials》2014
Multiwalled carbon nanotubes (MWCNTs) are cut short and grafted with polyethylenimine (PEI) for further covalent conjugation to fluorescein isothiocyanate (FITC) and prostate stem cell antigen (PSCA) monoclonal antibody (mAb). The in vitro and in vivo toxicity data reveal that the as-prepared CNT-PEI(FITC)-mAb has good biocompatibility. Combined flow cytometry and confocal luminescence imaging experiments confirm that the CNT-PEI(FITC)-mAb can specifically target the cancer cells which overexpress PSCA. The results of in vitro and in vivo ultrasound (US) imaging indicate that CNT-PEI(FITC)-mAb has great potential to be used as a targeted US contrast agent. The in vivo anti-cancer efficacy testing using PC-3 tumor-bearing mice as animal models demonstrates that CNT-PEI(FITC)-mAb can targetedly deliver drug to the tumors and suppress tumor growth. Findings from this study suggest that the CNT-PEI(FITC)-mAb could be used as a multifunctional platform for simultaneous US imaging and drug delivery applications. 相似文献
1000.
Poly(β-amino ester)s (PBAEs) represent an important class of cationic gene delivery materials which, however, suffer from uncontrolled DNA release due in part to the slow degradation of their polyester backbone. Additionally, PBAEs with high molecular weight (MW) also show considerable toxicities. In this study, we designed and developed PBAEs with trigger-responsive domains built-in polymer backbones that can be rapidly cleaved upon external UV light triggering to promote intracellular DNA release as well as reduce material toxicity. Photo-responsive PBAEs were prepared via polyaddition of (2-nitro-1,3-phenylene)bis(methylene) diacrylate and a bifunctional amine. The nitrobenzene moiety was placed in each repeating unit of the PBAE to allow fast response to external UV irradiation, and thus the ester linkers were cleaved and the polymers were degraded within several minutes upon UV irradiation. Cationic PBAEs with high MWs were able to mediate effective intracellular gene delivery, while upon UV irradiation post-transfection, enhanced DNA unpackaging and reduced material toxicity were observed, which collectively contributed to greatly improved transfection efficiencies in various mammalian cell types tested. This strategy allows precise manipulation of material toxicity and gene release profiles of PBAEs, and thus provides an effective design approach to address critical issues in non-viral gene delivery. 相似文献