Solvent replacement to thermo‐responsive nanoparticles from long‐subchain hyperbranched PSt grafted with PNIPAM for encapsulation

Long‐subchain hyperbranched polystyrene (lsc‐hp PSt) with uniform subchain length was obtained through copper‐catalyzed azide‐alkyne cycloaddition click chemistry from seesaw macromonomer of PSt having one alkynyl group anchored at the chain centre and two azido group attached to both chain ends [alkynyl‐(PSt‐N₃)₂]. After precipitation fraction, different portions of lsc‐hp PSt having narrow overall molecular weight distribution were obtained for further grafting with alkynyl‐capped poly(N‐isopropylacrylamide) (alkynyl‐PNIPAM), which was obtained via single‐electron transfer living radical polymerization of NIPAM with propargyl 2‐bromoisobutyrate as the initiator and grafted onto the peripheral azido groups of lsc‐hp PSt via click chemistry. Thus, amphiphilic lsc‐hp PSt grafted with PNIPAM chains (lsc‐hp PSt‐g‐PNIPAM) was obtained and would have star‐like conformation in tetrahydrofuran (THF). By replacing THF with water, lsc‐hp PSt‐g‐PNIPAM was dissolved at molecular level in aqueous solution due to the hydrophilicity of PNIPAM and exhibited thermal induced shrinkage of PNIPAM arms. The water‐insoluble lsc‐hp PSt would collapse densely and could be served as a reservoir to absorb hydrophobic chemicals in aqueous solution. The influence of overall molecular weight of lsc‐hp PSt on the absorption of pyrene was studied. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

胶体粒子的机械性能调控及其在药物递送中的应用

胶体粒子是肿瘤治疗中最常用的载体, 尽管在过去的研究中不同的胶体粒子已经被广泛报道, 但如何进一步提高胶体粒子的药物递送效率仍然存在着一些挑战. 大量的研究表明胶体粒子的尺寸、形状、结构和表面化学等物理化学性质在药物递送过程中具有重要的作用, 但胶体粒子的机械性能对药物递送过程的影响研究和综述相对较少. 本综述从不同机械性能胶体粒子的制备与表征出发, 概述了胶体粒子的机械性能对血液循环、肿瘤富集、渗透以及细胞内化过程的影响, 并对该领域存在的问题以及发展的趋势进行了展望. 该综述有助于帮助科学工作者更好地理解胶体粒子的机械性能对药物递送的影响规律, 从而优化胶体粒子的设计并提高纳米药物的递送效率和生物利用率.     

Cell–Membrane Penetration of Tat‐Conjugated Polymeric Micelles: Effect of Tat Coating Density

Considerable efforts have been devoted to enhancing the cell penetration of nanoparticles by coating cell‐penetrating peptides (CPPs) on the surface. However, the internalization mechanism for a CPP at different concentrations varies a lot. It is acknowledged that the mechanism is restricted to endocytic pathway at relatively low concentrations; however, direct translocation becomes dominant at high concentrations. This raises an interesting question on how the surface Tat coating density of the nanoparticles would influence their cell–membrane interaction and the consequent internalization behavior. This study systematically investigates the effect of Tat peptides on the internalization behavior of polymeric micelles by tuning surface Tat coating density, incubation concentrations, incubation time, and other factors using poly(ethylene glycol)–poly(ε‐caprolactone) copolymer (PEG‐PCL) micelles. It is found that both energy‐dependent and energy‐independent pathways are involved in the cellular uptake process, and the Tat‐conjugated polymeric micelles strongly accumulated on the cell surface at initial stage. The membrane‐anchoring and internalization rate increase with the increasing Tat coating density. Furthermore, the increasing of Tat coating density accelerates the energy‐independent pathway. It is envisioned that this finding will further shed light on the surface modification of nanoparticles for enhanced cell penetration and direct translocation into cell cytoplasm.     

Deciphering the Structure and Chemical Composition of Drug Nanocarriers: From Bulk Approaches to Individual Nanoparticle Characterization

Drug nanocarriers (NCs) with sizes usually below 200 nm are gaining increasing interest in the treatment of severe diseases such as cancer and infections. Characterization methods to investigate the morphology and physicochemical properties of multifunctional NCs are key in their optimization and in the study of their in vitro and in vivo fate. Whereas a variety of methods has been developed to characterize “bulk” NCs in suspension, the scope of this review is to describe the different approaches for the NC characterization on an individual basis, for which fewer techniques are available. The accent is put on methods devoid of labelling, which could lead to artefacts. For each characterization method, the principles and approaches to analyze the data are presented in an accessible manner. Aspects related to sample preparation to avoid artefacts are indicated, and emphasis is put on examples of applications. NC characterization on an individual basis allows gaining invaluable information in terms of quality control, on: i) NC localization and fate in biological samples; ii) NC morphology and crystallinity; iii) distribution of the NC components (drugs, shells), and iv) quantification of NCs’ chemical composition. The individual characterization approaches are expected to gain increasing interest in the near future.     

pH‐Triggered Charge‐Reversal Polyurethane Micelles for Controlled Release of Doxorubicin

A series of pH‐triggered charge‐reversal polyurethane copolymers (PS‐PUs) containing methoxyl‐poly(ethylene glycol) (mPEG), carboxylic acid groups, and piperazine groups is presented in this work. The obtained PS‐PUs copolymers can form into stable micelles at pH 7.4, which response to a narrow pH change (5.5–7.5) and show a tunable pH‐triggered charge‐reversal property. Doxorubicin (DOX) is encapsulated into the PS‐PU micelles as a model drug. The drug release of DOX‐loaded PS‐PU micelles shows an obviously stepped‐up with reducing the pH. Meanwhile, it is found that the charge‐reversal property can improve the cellular uptake behavior and intracellular drug release in both HeLa cells and MCF‐7 cells. Additionally, the time‐dependent cytotoxicity of the DOX‐loaded PS‐PU micelles is confirmed by MTT assay. Attributed to the tunable charge‐reversal property through changing the molar ratio of piperazine/carboxyl, the PS‐PU micelles will be a potential candidate as an intelligent drug delivery system in future studies.

     

基于纳米材料的基因载体

基因疗法是治疗基因变异引起的先天性遗传疾病和后天获得性疾病以及癌症的新型有效方法。外源基因在细胞中安全、高效、稳定的表达是基因治疗成功的关键,这与基因治疗所使用的载体系统息息相关。基因载体主要分为病毒载体和非病毒载体两大类:病毒载体的转染效率较高,但副作用较大;非病毒载体作为一种新型的基因传递系统,可以弥补病毒载体的缺陷,尽管其转染效率稍逊于病毒载体,但在基因治疗领域具有不可替代的作用。随着纳米技术的出现和蓬勃发展,基于纳米材料的基因载体研究受到越来越多的关注。纳米基因载体具有如下潜在的优势:它制备相对简单,易于对其进行多功能的修饰;具有良好的生物相容性,一般不会引起强烈的机体免疫反应;粒径普遍很小,容易穿过人体的组织间隙而被细胞吸收,基因转运效率较高;可以较有效保护其所携带外源基因,利于基因更高效地表达。本文主要对基于金属、无机非金属、阳离子聚合物和脂质体纳米材料作为基因载体的研究进展进行综述和展望。     

细胞膜伪装的纳米载体用于光热治疗的研究进展

纳米载体一直是肿瘤精准治疗的重要研究领域。其中以细胞膜伪装的纳米药物载体作为一种新颖的药物载体平台,在近年来已成为药物传递领域的研究热点。本文综述了不同种类细胞膜伪装的纳米载体应用于光热治疗的最新进展。将细胞膜与纳米材料结合起来,可进一步推进纳米载体的研究,这将对相关领域的发展产生重要影响。     

Silk Fibroin-Coated Liposomes as Biomimetic Nanocarrier for Long-Term Release Delivery System in Cancer Therapy

Despite much progress in cancer therapy, conventional chemotherapy can cause poor biodistribution and adverse side-effects on healthy cells. Currently, various strategies are being developed for an effective chemotherapy delivery system. Silk fibroin (SF) is a natural protein used in a wide range of biomedical applications including cancer therapy due to its biocompatibility, biodegradability, and unique mechanical properties. In this study, SF-coated liposomes (SF-LPs) were prepared as a biomimetic drug carrier. Physicochemical properties of SF-LPs were characterized by Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering, zeta potential measurement, and transmission electron microscopy (TEM). In vitro release of SF-LPs loaded with doxorubicin (DOX-SF-LPs) was evaluated over 21 days. Anticancer activity of DOX-SF-LPs was determined against MCF-7 and MDA-MB231 cells using the MTT assay. SF-LPs containing 1% SF exhibited favorable characteristics as a drug carrier. SF coating modified the kinetics of drug release and reduced the cytotoxic effect against L929 fibroblasts as compared to the uncoated liposomes containing cationic lipid. DOX-SF-LPs showed anticancer activity against breast cancer cells after 48 h or 72 h at 20 μM of DOX. This approach provides a potential platform of long-term release that combines biocompatible SF and phospholipids for cancer therapy, achieving efficient drug delivery and reducing side-effects.     

Octahydrogenated retinoic acid‐conjugated glycol chitosan nanoparticles as a novel carrier of azadirachtin: Synthesis,characterization, and in vitro evaluation

Environment‐friendly and controlled release formulation is highly promising for reducing environmental pollution and achieving the most effective utilization of pesticides. As a novel “green” nanocarrier of pesticides, amphiphilic self‐assembled nanoparticles were prepared by chemical conjugation of octahydrogenated retinoic acid (OR) to the backbone of glycol chitosan (GC). In aqueous media, the synthesized OR‐GC conjugates formed nanosized particles with a diameter of 257 nm. Hydrophobic azadirachtin (AZA) was efficiently loaded into the OR‐GC nanoparticles at a feed weight ratio of up to 1:4 using a simple dialysis method, the maximum drug‐loading efficiency of which was 74%. AZA‐OR‐GC (25 wt %) nanoparticles also showed sustained release of the incorporated AZA (65% of the loaded dose was released in 7 days at 27 °C in phosphate‐buffered saline; pH 7.2). Cytotoxicity tests and cell cycle arrest assays confirmed that OR‐GC exhibits good biocompatibility; AZA‐OR‐GC (25 wt %) nanoparticles also showed favorable inhibition of cell proliferation in Sl‐1 cells compared with free AZA in organic solvents. Overall, controlled release AZA‐OR‐GC may be a promising environment‐friendly formulation for integrated pest management. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 3932–3940     

Porphyrin Containing Polymersomes with Enhanced ROS Generation Efficiency: In Vitro Evaluation

Porphyrins are molecules possessing unique photophysical properties making them suitable for application in photodynamic therapy. The incorporation of porphyrins into natural or synthetic nano‐assemblies such as polymersomes is a strategy to improve and prolong their therapeutic capacities and to overcome their limitations as therapeutic and diagnostic agents. Here, 5,10,15,20‐tetrakis(1‐(6‐ethoxy‐6‐oxohexyl)‐4‐pyridin‐1‐io)‐21H,23H‐porphyrin tetrabromide porphyrin is inserted into polymersomes in order to demonstrate that the encapsulation enhances its ability to generate highly reactive singlet oxygen (¹O₂) upon irradiation in vitro. The photoactivation of the free and polymersome‐encapsulated porphyrin is evaluated by electron spin resonance and cell viability assays on three different mammalian cell lines. The results indicate that by encapsulating the porphyrin, a controlled ROS delivery within the cells is achieved, at the same time avoiding side effects such as dark toxicity, non‐specific porphyrin release and over time decreased activity in vitro. This work focuses on showing a not‐toxic model system for modern therapeutic nanomedicine, which works under mild irradiation and dosage conditions.