排序方式: 共有193条查询结果,搜索用时 31 毫秒
101.
Sparks SM Waite CL Harmon AM Nusblat LM Roth CM Uhrich KE 《Macromolecular bioscience》2011,11(9):1192-1200
New materials that can bind and deliver oligonucleotides such as short interfering RNA (siRNA) without toxicity are greatly needed to fulfill the promise of therapeutic gene silencing. Amphiphilic macromolecules (AMs) were functionalized with linear ethyleneimines to create cationic AMs capable of complexing with siRNA. Structurally, the parent AM is formed from a mucic acid backbone whose tetra-hydroxy groups are alkylated with 12-carbon aliphatic chains to form the hydrophobic component of the macromolecule. This alkylated mucic acid is then mono-functionalized with poly(ethylene glycol) (PEG) as a hydrophilic component. The resulting AM contains a free carboxylic acid within the hydrophobic domain. In this work, linear ethyleneimines were conjugated to the free carboxylic acid to produce an AM with one primary amine (1N) or one primary amine and four secondary amines (5N). Further, an AM with amine substitution both to the free carboxylic acid in the hydrophobic domain and also to the adjacent PEG was synthesized to produce a polymer with one primary amine and eight secondary amines (9N), four located on each side of the AM hydrophobic domain. All amine-functionalized AMs formed nanoscale micelles but only the 5N and 9N AMs had cationic zeta potentials, which increased with increasing number of amines. All AMs exhibited less inherent cytotoxicity than linear polyethyleneimine (L-PEI) at concentrations of 10 μM and above. By increasing the length of the cationic ethyleneimine chain and the total number of amines, successful siRNA complexation and cellular siRNA delivery was achieved in a malignant glioma cell line. In addition, siRNA-induced silencing of firefly luciferase was observed using complexes of siRNA with the 9N AM and comparable to L-PEI, yet showed better cell viability at higher concentrations (above 10 μM). This work highlights the promise of cationic AMs as safe and efficient synthetic vectors for siRNA delivery. Specifically, a novel polymer (9N) was identified for efficient siRNA delivery to cancer cells and will be further evaluated. 相似文献
102.
Wei Fu Lu Ma Yan Ju Jianguo Xu Hao Li Sirong Shi Tao Zhang Ronghui Zhou Jianwei Zhu Ruxiang Xu Chao You Yunfeng Lin 《Advanced functional materials》2021,31(33):2101435
Modulating microglial polarization is a potential strategy to assuage secondary brain injury caused by intracranial hemorrhage (ICH). However, despite decades of effort, effective therapies targeting microglia for ICH are still lacking. Here, a nanorobotic, tetrahedral framework nucleic acid (tFNA), is successfully synthesized and designed to carry C-C chemokine receptor 2 (siCCR2) for use in in vitro hemin-induced and in vivo collagenase-induced ICH models. This nanoscale complex (tFNA-siCCR2), which possesses biocompatibility, editability, and structural stability, exhibits a favorable effect in inhibiting the expression of CCR2. After treatment with tFNA-siCCR2, hematoma absorption is accelerated, and neurological inflammation is mitigated by decreasing levels of proinflammatory cytokines, while increasing the release of anti-inflammatory factors. Consequently, the neurological deficits of mice with ICH improve. These results indicate that inhibiting CCR2 expression during the acute phase of ICH polarizes microglia towards a therapeutic subtype, and restores neurological function, which demonstrates that tFNA has a promising ability to transfer siCCR2 for treating ICH. 相似文献
103.
Yanliang Dong Junhui Zhou Changrong Wang Yaping Wang Liandong Deng Jianhua Zhang Anjie Dong 《Macromolecular bioscience》2020,20(7)
Owing to the biodegradability and good biocompatibility polycarbonates show the versatile class of applications in biomedical fields. While their poor functional ability seriously limited the development of functional polycarbonates. Herein, a new Br‐containing cyclic carbonate (MTC‐Br) and a polycarbonate atom transfer radical polymerization (ATRP) macro‐initiator (PEG‐PMTC‐Br) is synthesized. Then, by initiating the side‐chain ATRP of 2‐(dimethyl amino)ethyl methacrylate (DMAEMA) on PEG‐PMTC‐Br, a series of comb‐like amphiphilic cationic polycarbonates, PEG‐b‐(PMTC‐g‐PDMAEMA) (GMDMs), with different lengths of cationic branches are successfully prepared. All these poly(ethylene glycol)‐b‐(poly((5‐methyl‐2‐oxo‐1,3‐dioxane‐5‐yl) methyl 2‐bromo‐2‐methylpropanoate/1,3‐dioxane‐2‐one)‐g‐poly(2‐dimethyl aminoethyl methacrylate) (GMDMs) self‐assembled nanoparticles (NPs) (≈180 nm, +40 mV) can well bind siRNA to form GMDM/siRNA NPs. The gene silence efficiency of GMDM/siRNA high to 80%, which is even higher than the commercial transfection reagent lipo2000 (76%). But GMDM/siRNA shows lower cell uptake than lipo2000. So, the high gene silence ability of GMDM/siRNA NPs can be attributed to the strong intracellular siRNA trafficking capacity. Therefore, GMDM NPs are potential siRNA vectors and the successful preparation of comb‐like polycarbonates also provides a facile way for diverse side‐chain functional polycarbonates, expanding the application of polycarbonates. 相似文献
104.
Muthusamy Jayaraman Steven M. Ansell Barbara L. Mui Ying K. Tam Jianxin Chen Xinyao Du David Butler Laxman Eltepu Shigeo Matsuda Jayaprakash K. Narayanannair Kallanthottathil G. Rajeev Ismail M. Hafez Akin Akinc Martin A. Maier Mark A. Tracy Pieter R. Cullis Thomas D. Madden Muthiah Manoharan Michael J. Hope 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2012,124(34):8657-8661
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利用涡旋混匀及室温孵育的方法制备了不同形貌的鱼精蛋白-siRNA复合体, 并利用聚丙烯酰胺凝胶电泳结合银染、 原子力显微镜和透射电子显微镜等手段进行了结构表征. 结果表明, 鱼精蛋白可以和不同的siRNA分子以不同的质量比形成球形和纤维状鱼精蛋白-siRNA复合物. 在此基础上, 利用Mg2+等金属离子探针, 确认鱼精蛋白与siRNA的磷酸-戊糖骨架之间通过静电力发生作用. 利用原子力和透射电子显微镜表征了鱼精蛋白-siRNA复合体的形貌和结构特征; 利用激光纳米粒度仪测量了该复合体的粒径; 并进一步比较了黑色素瘤细胞对不同形貌复合体的吞噬及药效学特征. 相似文献
108.
So Jin Lee Dr. Myung Sook Huh Seung Young Lee Solki Min Dr. Seulki Lee Dr. Heebeom Koo Dr. Jun‐Uk Chu Dr. Kyung Eun Lee Dr. Hyesung Jeon Dr. Yongseok Choi Dr. Kuiwon Choi Dr. Youngro Byun Dr. Seo Young Jeong Dr. Kinam Park Dr. Ick Chan Kwon 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2012,124(29):7315-7319
109.
Yuanyuan Yuan Yiyao Wang Huiling Huang Shuiliang Tao Jinsheng Huang 《Macromolecular bioscience》2023,23(4):2200529
Successful clinical application of siRNA to liver-associated diseases reinvigorates the RNAi therapeutics and delivery vectors, especially for anticancer combination therapy. Fine tuning of copolymer-based assembly configuration is highly important for a desirable synergistic cancer cell-killing effect via the codelivery of chemotherapeutic drug and siRNA. Herein, an amphiphilic triblock copolymer methoxyl poly(ethylene glycol)-block-poly(L-lysine)-block-poly(2-(diisopropyl amino)ethyl methacrylate) (abbreviated as mPEG-PLys-PDPA or PLD) consisting of a hydrophilic diblock mPEG-PLys and a hydrophobic block PDPA is synthesized. Three distinct assemblies (i.e., nanosized micelle, nanosized polymersome, and microparticle) are acquired, along with the increase in PDPA block length. Furthermore, the as-obtained polymersome can efficiently codeliver doxorubicin hydrochloride (DOX) as a hydrophilic chemotherapeutic model and siRNA against ADP-ribosylation factor 6 (siArf6) as an siRNA model into cancer cell via lysosomal pH-triggered payload release. PC-3 prostate cell is synergistically killed by the DOX- and siArf6-coloading polymersome (namely PLD@DOX/siArf6). PLD@DOX/siArf6 may serve as a robust nanomedicine for anticancer therapy. 相似文献
110.
Jing Gao Hanwu Zhang Fengqi Zhou Bo Hou Meiwan Chen Zhigang Xie Haijun Yu 《中国化学快报》2021,32(6):1929-1936
Cyclin-dependent kinases 4 and 6 inhibitors(CDK4/6i) have been demonstrated to trigger antitumor immunity for tumor regression. However, the therapeutic performance of CDK4/6i-meadiated cancer immunotherapy was impaired by the immunosuppressive tumor microenvironment(ITM) due to overexpression of programmed death ligand 1(PD-L1) on the surface of cancer cell membrane. To improve the immunotherapeutic performance of CDK4/6i, we herein developed endosomal acidactivatable micelleplex for si RNA delivery and PD-L1 knockdown in the tumor cells in vitro and in vivo. We further demonstrated that the combination of PD-L1 knockdown and CDK4/6 inhibition facilitated intratumoral infiltration of cytotoxic T lymphocytes(CTLs), and elicited protective immune response and efficiently suppressed tumor growth in vivo. This study revealed the importance of molecular design of the micelleplex for highly efficient si RNA delivery, which might provide a novel insight for RNAi-based cancer immunotherapy. 相似文献