无机纳米药物载体在肿瘤诊疗中的研究进展

纳米药物作为一种新兴技术,为肿瘤的精确定位和早期诊断、靶向、长效和联合治疗提供了重要的研发平台,为克服传统药物非特异性靶向和非选择性损伤机体组织的瓶颈问题提供了可能。近年来研究者基于量子点、纳米金、纳米介孔硅等无机纳米药物载体设计合成了大量可用于肿瘤诊疗的纳米药物,主要通过"核-壳"结构设计、表面修饰等方法提高纳米药物性能。综述了无机纳米材料作为纳米药物载体在肿瘤诊疗中的应用,详细介绍了纳米药物的设计策略和肿瘤诊疗作用机制,并对未来进行无机纳米药物在肿瘤诊疗中的临床应用进行了展望。     

介孔硅纳米载体应用于肿瘤治疗的研究进展

化疗是临床上治疗恶性肿瘤的重要手段，但化疗药物毒副作用大、易产生耐药和生物相容性差等问题往往限制其治疗效果。纳米载体可使药物靶向作用于肿瘤部位，减少化疗药物对正常组织产生的毒副作用，从而提高治疗效果，近年来已成为癌症精准治疗领域中的研究热点。其中，介孔硅纳米粒子(Mesoporous silica nanoparticles, MSNs)作为一种无机纳米材料，具有比表面积大、孔径可调、孔体积大、生物相容性好和易于功能化修饰等优点，被广泛用于纳米递送系统的构建，尤其是集肿瘤靶向、治疗和成像等多种功能于一体的新型纳米递送系统。综述了近年来功能化MSNs递送载体应用于肿瘤靶向治疗、药物递送和肿瘤生物成像等方面的研究进展，为开发新型纳米递送系统以用于癌症治疗提供了参考。     

智能响应型纳米药物载体的研究进展

近年来智能响应型纳米药物载体在抗肿瘤药物的递送中得到了广泛关注。该文根据智能响应型纳米药物载体是否具有主动靶向性,将其分为非靶向智能响应型纳米药物载体和靶向智能响应型纳米药物载体,并分别对这两者纳米药物载体的新研究和新进展进行了综述。同时,总结了智能响应型纳米药物载体当前存在的问题。与非靶向智能响应型纳米药物载体相比,靶向智能响应型纳米药物载体具有更多的优势,尤其是靶向肿瘤组织中特异性过表达酶的智能响应型纳米药物载体将会是今后纳米药物载体研究的一个重要方向。     

磁性纳米颗粒的制备及在靶向药物传输领域的应用

磁性纳米粒子因其独特的物理化学性质引起了研究人员的广泛兴趣,近年来在生物医学领域的潜在应用也受到了极大关注。通过载体传输的方法将药物靶向递送至病变部位,以减少对正常部位的副作用。为了提高药物的药效学作用并减少其毒性和副作用,靶向药物递送和缓释已成为关注的焦点。作为药物递送工具,磁性纳米颗粒提供了被靶向的可能性。在本文中我们简要的介绍了磁性纳米颗粒常见的合成方法及作为药物载体的优点。     

pH敏感型聚合物胶束作为药物载体研究进展

近年来,刺激响应型聚合物胶束作为纳米药物载体因其独特的优势,如具有靶向性高、良好的生物相容性和毒副作用小等优势,而应用于药物靶向治疗中,其中pH敏感型聚合物胶束是基于生理条件下包载药物,特定pH条件下释放药物,而达到药物靶向释放目的。本文主要综述pH敏感型聚合物胶束的种类、特性、应用于药物靶向治疗的原理和研究进展,为开发和应用pH敏感型聚合物胶束提供参考。     

作为药物载体的聚氨酯纳米胶束的研究进展

聚氨酯材料具有生物相容性好、合成简单且分子结构可设计性强等优点,不可降解的聚氨酯材料在生物医学领域已经得到应用。目前可生物降解聚氨酯纳米胶束用作药物载体的研究受到广泛关注。本综述主要从生物相容性、刺激响应性、靶向作用、细胞摄取能力强的聚氨酯纳米胶束这几个方面,介绍了作为药物载体的可生物降解聚氨酯纳米胶束的研究进展。     

RGD肽偶联材料在实体瘤治疗中的应用

化疗药物的渗透性差和非选择性分布是实体癌化疗的主要障碍。近年来，很多研究通过RGD肽及其衍生物与药物分子或载体材料偶联再形成纳米药物来增加化疗药物的肿瘤靶向性及肿瘤渗透性来改善实体癌的治疗效果。本文介绍了实体癌治疗障碍，分析了RGD肽及其衍生物的作用机制，并对其与药物分子及脂质材料偶联形成的靶向材料在实体癌治疗中的应用及研究进展进行了综述。     

TiO2纳米结构作为载体在药物缓控释传递系统的应用

TiO₂纳米结构以其生物相容性好、机械强度高、耐热耐腐蚀等优点,在药物缓控释传递系统载体应用方面引起广泛关注。结合近几年研究报道,本文将单一和功能化TiO₂纳米结构作为药物缓控释载体进行分类,简述了制备方法、结构表征、载药方法、释药机理等,分析了功能化TiO₂纳米结构修饰结合外界刺激响应在药物缓控释系统的应用。结果表明,相比单一结构,功能化修饰后的TiO₂纳米结构具有载药率高、缓控释效果明显、生物相容性好等优点;功能化修饰结合外界刺激响应,进一步提升药物缓控释效果;而相比单一和双重刺激响应,多重刺激响应能够更好地实现局部靶向释药。最后预测该纳米结构作为药物缓控释传递系统载体的研究发展方向并指出目前实现临床应用所面临的问题。     

细胞靶向抗肿瘤纳米药物载体的研究进展

肿瘤已经成为严重危害人类健康的重大疾病之一,而如何治疗肿瘤疾病已逐渐变为近年内的研究热点。由于纳米药物载体在细胞靶向抗肿瘤中表现出来的特殊性质,使其受到了越来越多的关注。本文将就一些常见的纳米药物载体作一综述。     

基于合成高分子的纳米药物载体的研究进展

基于合成高分子的纳米微粒由于其良好的生物相容性、生物可降解性和粘膜粘附性等特点成为药物载体研究的热．董。根据构建纳米药物载体的高分子聚合物结构的差异,将其分为：基于两亲聚合物的纳米微粒（胶团和囊泡）、脂质体、树枝状或超支化大分子、乳液聚合纳米微粒,并对上述纳米微粒作为药物载体在近年来的研究进展进行了归纳和总结．展望了其在药物缓释体系中的广阔应用前景。     

A novel interfacial thermodynamic model for predicting solubility of nanoparticles coated by stabilizers

To improve the stability of nanoparticles in aqueous solution, polymer or surfactant, etc. are often added in solutions during the preparation process of nanoparticles, which can induce new interfaces that influence the solubility of nanoparticles. In this work, a novel interfacial thermodynamic model for describing the Gibbs energy of the nanoparticles coated by stabilizers was proposed to predict the solubility of nanoparticles. Within the developed model, the activity coefficient of nano metal system was determined by Davies model and that of nano drug system by Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT). The Gibbs energy of the interface was established as a function of molecular parameters via the application for nano metal system. Furthermore, the model was further used to predict the solubility of nano drugs itraconazole, fenofibrate, and griseofulvin. It was found that the Gibbs energy of the interface plays an important role especially when the radius of nano metal is less than 40 nm, and the developed model can predict the solubility of nano drug with high accuracy in comparison with the experimental data as well as predict the changing trend of solubility of nano drugs that increases as the particle size decreases. Meanwhile, the stabilization mechanism of stabilizers on nano drugs was studied which provided theoretical guidance for the selection of polymer or surfactant stabilizer. These findings showed that the developed model can provide a reliable prediction of the solubility of nanoparticles and help to comprehend the stabilization mechanism of the stabilizers on nano drugs with different particle sizes, which is expected to provide important information for the design of nano drugs formulations.     

Novel Strategies for Nanoparticle-Based Radiosensitization in Glioblastoma

Radiotherapy (RT) is one of the cornerstones in the current treatment paradigm for glioblastoma (GBM). However, little has changed in the management of GBM since the establishment of the current protocol in 2005, and the prognosis remains grim. Radioresistance is one of the hallmarks for treatment failure, and different therapeutic strategies are aimed at overcoming it. Among these strategies, nanomedicine has advantages over conventional tumor therapeutics, including improvements in drug delivery and enhanced antitumor properties. Radiosensitizing strategies using nanoparticles (NP) are actively under study and hold promise to improve the treatment response. We aim to describe the basis of nanomedicine for GBM treatment, current evidence in radiosensitization efforts using nanoparticles, and novel strategies, such as preoperative radiation, that could be synergized with nanoradiosensitizers.     

Acidity and Glutathione Dual-Responsive Polydopamine-Coated Organic-Inorganic Hybrid Hollow Mesoporous Silica Nanoparticles for Controlled Drug Delivery

Controversial biodegradability and nonspecific pre-drug leakage are major limitations for inorganic nanoparticles in cancer treatment. To solve these problems, we developed organic-inorganic hybridized hollow mesoporous silica nanoparticles with polydopamine modifications on the surface to simultaneously achieve enhanced biodegradability and controllable drug release. The morphology and chemical structure of the nanoparticles were characterized by TEM, N₂ adsorption-desorption isotherms, TEM-mapping and XPS. Moreover, the release behavior of nanoparticles under various pH conditions and the degradation behavior in the presence of GSH were evaluated. With effective controlled release, HMONs-PTX@PDA were shown to significantly inhibit cancer cell proliferation and achieve antitumor effects in vivo through dual-response release in the tumor microenvironment. Overall, this nanoplatform has significant potential to achieve tumor microenvironment-responsive degradation and release to enhance tumor accumulation, which is very promising for cancer treatment.     

In vivo targeted delivery of nanoparticles for theranosis

Therapy and diagnosis are two major categories in the clinical treatment of disease. Recently, the word "theranosis" has been created, combining the words to describe the implementation of these two distinct pursuits simultaneously. For successful theranosis, the efficient delivery of imaging agents and drugs is critical to provide sufficient imaging signal or drug concentration in the targeted disease site. To achieve this purpose, biomedical researchers have developed various nanoparticles composed of organic or inorganic materials. However, the targeted delivery of these nanoparticles in animal models and patients remains a difficult hurdle for many researchers, even if they show useful properties in cell culture condition. In this Account, we review our strategies for developing theranostic nanoparticles to accomplish in vivo targeted delivery of imaging agents and drugs. By applying these rational strategies, we achieved fine multimodal imaging and successful therapy. Our first strategy involves physicochemical optimization of nanoparticles for long circulation and an enhanced permeation and retention (EPR) effect. We accomplished this result by testing various materials in mouse models and optimizing the physical properties of the materials with imaging techniques. Through these experiments, we developed a glycol chitosan nanoparticle (CNP), which is suitable for angiogenic diseases, such as cancers, even without an additional targeting moiety. The in vivo mechanism of this particle was examined through rationally designed experiments. In addition, we evaluated and compared the biodistribution and target-site accumulation of bare and drug-loaded nanoparticles. We then focus on the targeting moieties that bind to cell surface receptors. Small peptides were selected as targeting moieties because of their stability, low cost, size, and activity per unit mass. Through phage display screening, the interleukin-4 receptor binding peptide was discovered, and we combined it with our nanoparticles. This product accumulated efficiently in atherosclerotic regions or tumors during both imaging and therapy. We also developed hyaluronic acid nanoparticles that can bind efficiently to the CD44 antigen receptors abundant in many tumor cells. Their delivery mechanism is based on both physicochemical optimization for the EPR effect and receptor-mediated endocytosis by their hyaluronic acid backbone. Finally, we introduce the stimuli-responsive system related to the chemical and biological changes in the target disease site. Considering the relatively low pH in tumors and ischemic sites, we applied pH-sensitive micelle to optical imaging, magnetic resonance imaging, anticancer drug delivery, and photodynamic therapy. In addition, we successfully evaluated the in vivo imaging of enzyme activity at the target site with an enzyme-specific peptide sequence and CNPs. On the basis of these strategies, we were able to develop self-assembled nanoparticles for in vivo targeted delivery, and successful results were obtained with them in animal models for both imaging and therapy. We anticipate that these rational strategies, as well as our nanoparticles, will be applied in both the diagnosis and therapy of many human diseases. These theranostic nanoparticles are expected to greatly contribute to optimized therapy for individual patients as personalized medicine, in the near future.     

Functional dendrimer–gold nanoparticle hybrids for biomedical applications

Dendrimers are a class of nano‐sized synthetic polymers with a well‐defined composition and regularly branched tree‐like structure produced by stepwise growth. The uniform size, globular shape and tunable surface chemistry make dendrimers versatile nanoscaffolds to encapsulate or stabilize various inorganic (metal, metal oxide, semiconductor) nanoparticles. In the past decade, research interest in dendrimer–inorganic nanoparticle hybrids has evolved from the development of interesting properties to the exploitation of advanced and useful functions. In particular, because gold nanoparticles with controlled morphology and optical properties have been demonstrated to be promising and versatile candidates for a diverse field of biomedical applications including sensing, in vitro and in vivo imaging, drug delivery, diagnostics and therapies, dendrimer–gold nanoparticle hybrids with biocompatibility have recently been intensively investigated for promising biomedical applications due to their controllable structures and dimensions, as well as their desirable internal and/or external functionalities. In this review, we discuss the recent progress regarding the development of functional dendrimer–gold nanoparticle hybrids for biomedical applications. The strategies for the fabrication of various structures of dendrimer–gold nanoparticle hybrids will first be summarized, followed by their biomedical applications in drug and gene delivery, photothermal therapy and combined therapies. © 2018 Society of Chemical Industry     

Development of Core-Shell Nanoparticle Drug Delivery Systems Based on Biomimetic Mineralization

Among various drug-delivery systems, core-shell nanoparticles have many advantages. Inspired by nature, biomimetic synthesis has emerged as a new strategy for making core-shell nanoparticles in recent years. Biomimetic mineralization is the process by which living organisms produce minerals based on biomolecule templating that leads to the formation of hierarchically structured organic–inorganic materials. In this minireview, we mainly focus on the synthesis of core-shell nanoparticle drug-delivery systems by biomimetic mineralization. We review various biomimetic mineralization methods for fabricating core-shell nanoparticles including silica-based, calcium-based and other nanoparticles, and their applications in drug delivery. We also summarize strategies for drug loading in the biomolecule-mineralized core-shell NPs. Current challenges and future directions are also discussed.     

血小板膜伪装介孔聚多巴胺纳米药物传递系统的制备及应用

以三甲基苯为模板剂,采用一锅法制备了具有介孔结构的聚多巴胺纳米粒子(MPDA).通过静电吸附负载盐酸阿霉素(DOX),通过血小板膜(PLTM)仿生伪装得到PLTM-DOX@MPDA纳米粒子.采用TEM、纳米粒度分析仪、BET和UV-Vis对纳米粒子的性质、形貌和粒径进行表征.结果表明,MPDA表面具有清晰的介孔结构,经PLTM包裹后的PLTM-DOX@MPDA平均粒径约为184 nm.MPDA孔径主要分布于45 nm左右,孔容为0.6232 cm3/g,比表面积高达61.181 m2/g,该介孔结构支持MPDA作为高效的药物传递系统.体外释药、体外细胞摄取和体外细胞毒性实验结果表明,PLTM-DOX@MPDA具有pH响应性控制药物释放,可以实现药物缓释,可以避免巨噬细胞吞噬并且主动靶向癌细胞,可显著提高DOX对人乳腺癌细胞(MDA-MB-231)细胞的杀伤作用.     

SMA-纳米SiC及SMA-纳米金刚石复合膜制备及其Cu2+离子吸附性能

以纳米SiC及纳米金刚石粉体为添加剂,通过苯乙烯与顺丁烯二酸酐的聚合,成功制备了苯乙烯-马来酸酐-纳米碳化硅(SMA-纳米SiC)及苯乙烯-马来酸酐-纳米金刚石(SMA-nano diamond)复合薄膜材料。通过热重分析(TG)、傅里叶红外光谱仪(FTIR)和扫描电子显微镜(SEM)对吸附复合膜的结构进行表征。研究了SMA-纳米SiC及SMA-纳米金刚石复合膜的吸水性及其对二价铜(Cu²⁺)离子的吸附特性。结果表明,无机纳米颗粒的添加均提高了复合薄膜的耐热特性,提高了热分解温度。当纳米粉体含量在0.8~1.2 g之间,可以获得较为均匀的泡沫状多孔复合薄膜。浸泡6 h,纳米SiC添加量为1.0 g的复合膜吸水率低至4.81%。纳米金刚石添加量为1.0 g,复合膜吸水率低至3.52%。适量的纳米SiC及纳米金刚石可以提高复合膜的耐水性能。SMA-纳米SiC及SMA-纳米金刚石复合膜材料均对Cu²⁺离子具有一定的吸附特性,泡沫状复合膜吸附性能最佳。纳米SiC及纳米金刚石能够有效改善SMA膜对重金属离子的吸附性能。     

Bioengineered Ferritin Nanocarriers for Cancer Therapy

Ferritin naturally exists in most organisms and can specifically recognize the transferrin 1 receptor (TfR1), which is generally highly expressed on various types of tumor cells. The pH dependent reversible assembling and disassembling property of ferritin renders it as a suitable candidate for encapsulating a variety of anticancer drugs and imaging probes. Ferritins external surface is chemically and genetically modifiable which can serve as attachment site for tumor specific targeting peptides or moieties. Moreover, the biological origin of these protein cages makes it a biocompatible nanocarrier that stabilizes and protects the enclosed particles from the external environment without provoking any toxic or immunogenic responses. Recent studies, further establish ferritin as a multifunctional nanocarrier for targeted cancer chemotherapy and phototherapy. In this review, we introduce the favorable characteristics of ferritin drug carriers, the specific targeted surface modification and a multifunctional nanocarriers combined chemotherapy with phototherapy for tumor treatment. Taken together, ferritin is a potential ideal base of engineered nanoparticles for tumor therapy and still needs to explore more on its way.     

纳米粒子增韧聚氯乙烯的研究

综述了纳米粒子在聚氯乙烯(PVC)增韧改性中的研究现状及作用机理,分别介绍了纳米CaCO3、纳米SiO2、纳米黏土及“核壳”纳米粒子等在PVC增韧改性中的研究与应用,得出了纳米复合技术在PVC增韧改性中均能提高材料韧性和强度的特点。最后,对发展价格低廉的新型纳米增韧增强粒子进行了展望。