Nanoparticles for the delivery of zoledronic acid to prostate cancer cells: A comparative analysis through time lapse video-microscopy technique

Time-lapse live cell imaging is a powerful tool for studying the responses of cells to drugs. Zoledronic acid (ZOL) is the most potent aminobiphosphonate able to induce cell growth inhibition at very low concentrations. The lack of clear evidence of ZOL-induced anti-cancer effects is likely due to its unfavorable pharmacokinetic profile. The use of nanotechnology-based formulations allows overcoming these limitations in ZOL pharmaco-distribution. Recently, stealth liposomes (LIPOs) and new self-assembly PEGylated nanoparticles (NPs) encapsulating ZOL were developed. Both the delivery systems showed promising anticancer activity in vitro and in vivo.In this work, we investigated the cytostatic effect of these novel formulations (LIPOs and NPs) compared with free ZOL on 2 different prostate cancer cell lines, PC 3 and DU 145 and on prostate epithelial primary cells EPN using time lapse video-microscopy (TLVM). In PC3 cells, free ZOL showed a significant anti-proliferative effect but this effect was lower than that induced by LIPOs and NPs encapsulating ZOL; moreover, LIPO-ZOL was more potent in inducing growth inhibition than NP-ZOL. On the other hand, LIPO-ZOL slightly enhanced the free ZOL activity on growth inhibition of DU 145, while the anti-proliferative effect of NP-ZOL was not statistically relevant. These novel formulations did not induce anti-proliferative effects on EPN cells. Finally, we evaluated cytotoxic effects on DU145 where, LIPO-ZOL induced the highest cytotoxicity compared with NP-ZOL and free ZOL. In conclusion, ZOL can be transformed in a powerful anticancer agent, if administered with nanotechnology-based formulations without damaging the healthy tissues.     

双亲性无规共聚物P(VM-co-AMPS)的自组装及其性能

将γ-环糊精（γ-CD）和3种不同长度烷基（C_n,n为12,16,18）分别按照一定的接枝率接枝于聚丙烯酸链上,利用环糊精与疏水烷基链之间的包合作用,成功制备了大分子自组装网络,并利用流变学手段对影响高分子网络结构的因素进行了系统研究。结果表明：γ-CD与Cn之间的包合作用主要以1∶2的量化模式进行,即1个γ环糊精空腔可以同时穿入2条烷基链。当聚合物的质量分数较低时(w≤1.7%),聚合物之间以包合作用交联为主;随着聚合物质量分数的增加并超过临界浓度,疏水缔合作用产生且迅速增大,并最     

Natural tri- to hexapeptides self-assemble in water to amyloid beta-type fiber aggregates by unexpected alpha-helical intermediate structures

Many fatal neurodegenerative diseases such as Alzheimer's, Parkinson, the prion-related diseases, and non-neurodegenerative disorders such as type II diabetes are characterized by abnormal amyloid fiber aggregates, suggesting a common mechanism of pathogenesis. We have discovered that a class of systematically designed natural tri- to hexapeptides with a characteristic sequential motif can simulate the process of fiber assembly and further condensation to amyloid fibrils, probably via unexpected dimeric α-helical intermediate structures. The characteristic sequence motif of the novel peptide class consists of an aliphatic amino acid tail of decreasing hydrophobicity capped by a polar head. To our knowledge, the investigated aliphatic tripeptides are the shortest ever reported naturally occurring amino acid sequence that can adopt α-helical structure and promote amyloid formation. We propose the stepwise assembly process to be associated with characteristic conformational changes from random coil to α-helical intermediates terminating in cross-β peptide structures. Circular dichroism and X-ray fiber diffraction analyses confirmed the concentration-dependent conformational changes of the peptides in water. Molecular dynamics simulating peptide behavior in water revealed monomer antiparallel pairing to dimer structures by complementary structural alignment that further aggregated and stably condensed into coiled fibers. The ultrasmall size and the dynamic facile assembly process make this novel peptide class an excellent model system for studying the mechanism of amyloidogenesis, its evolution and pathogenicity. The ability to modify the properties of the assembled structures under defined conditions will shed light on strategies to manipulate the pathogenic amyloid aggregates in order to prevent or control aggregate formation.     

Instant fabrication and selection of folded structures using drop impact

A drop impacting a target cutout in a thin polymer film is wrapped by the film in a dynamic sequence involving both capillary forces and inertia. Different 3D structures can be produced from a given target by slightly varying the impact parameters. A simplified model for a nonlinear dynamic Elastica coupled with a drop successfully explains this shape selection and yields detailed quantitative agreement with experiments. This first venture into the largely unexplored dynamics of elastocapillary assemblies opens up the perspective of mass production of 3D packages with individual shape selection.     

Lateral sorting in model membranes by cholesterol-mediated hydrophobic matching

Theoretical studies predict hydrophobic matching between transmembrane domains of proteins and bilayer lipids to be a physical mechanism by which membranes laterally self-organize. We now experimentally study the direct consequences of mismatching of transmembrane peptides of different length with bilayers of different thicknesses at the molecular level. In both model membranes and simulations we show that cholesterol critically constrains structural adaptations at the peptide-lipid interface under mismatch. These constraints translate into a sorting potential and lead to selective lateral segregation of peptides and lipids according to their hydrophobic length.     

Mineralized Collagen: Rationale,Current Status,and Clinical Applications

This paper presents a review of the rationale for the in vitro mineralization process, preparation methods, and clinical applications of mineralized collagen. The rationale for natural mineralized collagen and the related mineralization process has been investigated for decades. Based on the understanding of natural mineralized collagen and its formation process, many attempts have been made to prepare biomimetic materials that resemble natural mineralized collagen in both composition and structure. To date, a number of bone substitute materials have been developed based on the principles of mineralized collagen, and some of them have been commercialized and approved by regulatory agencies. The clinical outcomes of mineralized collagen are of significance to advance the evaluation and improvement of related medical device products. Some representative clinical cases have been reported, and there are more clinical applications and long-term follow-ups that currently being performed by many research groups.     

医用不锈钢表面生物活性纳米多层膜的制备及血液相容性

为改善人体内金属植入物的生物相容性,采用静电自组装的方法在医用316L不锈钢表面制备出聚乙烯亚胺(PEI)与透明质酸(HA)复合的生物活性纳米多层膜.小角X射线衍射结果显示多层膜呈现出层层规则排列,运用原子力显微镜对涂层的表面形貌以及粗糙度分析证明随着层数的增加表面形貌得到改善,由粗糙逐渐变得平滑.对涂层进行血小板黏附实验表明该纳米多层膜血小板黏附明显降低、血液相容性明显得到改善.     

层层静电自组装表面修饰静电纺丝人工血管的生物相容性研究

背景大、中口径人工血管已成功用于临床,但是由于材料的疏水性小口径人工血管仍不能满足临床的需要。因此,提高人工血管材料的亲水性、抗凝血性一直是医学界研究的热点。目的研究静电自组装修饰后的电纺丝纤维膜的形貌特征、细胞相容性和组织相容性。方法利用静电自组装技术将壳聚糖和肝素修饰到静电纺丝聚乳酸纤维膜表面,通过扫描电镜观察组装前后电纺丝纤维的形貌特征;将人脐静脉内皮细胞种植与组装前后的纤维膜上,通过MTT测试检测细胞增殖能力;通过将组装前后不同材料植入兔皮下15天,通过HE染色检测其组织相容性。结果 SEM结果显示,成功将壳聚糖/肝素组装到电纺丝纤维膜表面。MTT结果显示组装后的电纺丝纤维膜促进HUVEC的增殖。兔皮下植入实验结果显示组装修饰后的电纺丝膜具有良好的组织相容性。结论静电自组装成功应用于静电纺丝中,并且电纺丝纤维膜经修饰后成功提高材料的细胞相容性和组织相容性。