纳米递送系统线粒体靶向策略在肿瘤诊疗中的应用

肿瘤是危害人类健康的重大疾病之一。目前用于肿瘤治疗的方法有手术治疗、化学药物治疗、放射治疗等。然而,传统的治疗方法存在治疗效果不佳、易引发多药耐药、毒副作用大等缺点,仍需进一步探索新的肿瘤治疗靶点和策略。线粒体作为细胞的能量转换器,被认为是肿瘤、心血管和神经性疾病新药设计的最重要靶点之一。纳米药物递送载体具有易被主动靶向基团修饰的特点,可实现细胞乃至细胞器的精准靶向给药。本文从抑制肿瘤细胞增殖、促进肿瘤细胞凋亡、抑制肿瘤复发与转移、诱导细胞自噬等方面综述了线粒体靶向纳米载体在肿瘤诊疗中的应用。     

磁性氧化铁纳米药物载体的研究进展

近年来,磁性氧化铁靶向纳米载体作为载药系统引起了人们的关注。磁性靶向载药系统和靶向药物治疗的目的是药物载体载药后,在外部磁场的作用下直接靶向富集在肿瘤或病损组织,杀伤病损细胞,对人体无害或减少毒副作用。本文介绍了影响磁纳米颗粒在体内作用的设计参数,并总结了被广泛应用于氧化铁纳米颗粒的制备,表面修饰,功能化的方法及氧化铁纳米载体在靶向载药体系中的应用。     

磁性氧化铁纳米药物载体的研究进展

近年来,磁性氧化铁靶向纳米载体作为载药系统引起了人们的关注。磁性靶向载药系统和靶向药物治疗的目的是药物载体载药后,在外部磁场的作用下直接靶向富集在肿瘤或病损组织,杀伤病损细胞,对人体无害或减少毒副作用。本文介绍了影响磁纳米颗粒在体内作用的设计参数,并总结了被广泛应用于氧化铁纳米颗粒的制备,表面修饰,功能化的方法及氧化铁纳米载体在靶向载药体系中的应用。     

肿瘤靶向纳米载药系统的设计与构建

近年来将纳米载药系统应用于肿瘤靶向递药的研究层出不穷。与正常组织相比,肿瘤组织具有较低的pH环境、大量新生血管生成、 不规则的血流灌注、局部缺氧等特异性的微环境,利用这些特点进行合理的纳米载药系统设计能够实现肿瘤部位的高效递药及深层穿透, 显著提高肿瘤治疗效果。针对现有的肿瘤靶向纳米载药系统的构建与设计方法进行综述,以阐述纳米载药系统在肿瘤靶向传递中的研究进展     

基于磁性纳米材料的肿瘤靶向治疗研究进展

磁性纳米材料具有独特的磁学性质，可响应外磁场，产生力、热等效应。如在静磁场下将药物磁靶向递送至肿瘤部位；低频交变磁场下可将纳米药物主动渗透至病灶部位，实现瘤内均一分布；中频交变磁场作用下磁滞损耗产生热和增强的活性氧，用于肿瘤治疗。磁性纳米材料同时具有尺寸依赖的磁学性质以及表面多功能化等特点，可将磁靶向、分子靶向以及磁热疗联合。此外，磁性纳米材料具有磁共振成像性能以及纳米酶催化特性，使其在肿瘤诊疗一体化治疗方面获得了广泛应用。近年来，纳米给药系统不断被优化，基于磁性纳米材料的肿瘤靶向治疗也得到了长足的发展。鉴于此，本文围绕提高靶向肿瘤治疗效果，从磁靶向药物治疗、被动靶向磁热疗和主动分子靶向磁热疗、纳米酶特性以及诊疗一体化应用等几方面出发，综述了基于磁性纳米材料的肿瘤靶向治疗研究进展。     

微针用于生物大分子及纳米药物透皮给药的尝试与挑战

生物大分子及纳米药物,比如,亚单位疫苗、DNA疫苗、以及针对真皮层的治疗药物,作为近年来新兴的治疗药物,在有些治疗领域有着透皮给药的需求。由于具有靶向性高,疗效显著等特点,生物大分子及纳米药物逐渐成为新的研究热点。微针作为一种新型的给药技术,不仅具有无痛、给药方便等优点,而且运用物理手段可大幅提高大分子甚至纳米药物的透皮吸收及皮层靶向,能够避过胃肠道消化作用以及肝脏首过效用。将微针技术与生物大分子药物相结合,能够同时发挥两者的优势,实现高靶向生物药物的无痛给药。本文简述微针透皮给药技术、以及生物大分子给药的研究进展,对微针技术用于生物大分子及纳米药物透皮给药的尝试研究做了介绍和总结,对存在的技术挑战进行了分析和展望。     

新模式肿瘤纳米诊疗一体化

纳米诊疗一体化是恶性肿瘤精准治疗的重要研究方向之一。通过纳米载体实现的可视化药物递送和治疗监控,在肿瘤诊断和治疗过程中具有独特优势。本文归纳了近年来纳米诊疗一体化发展的新模式及其研究现状,旨在为推动纳米诊疗一体化的进一步应用提供参考。     

杂交鹅掌楸悬浮细胞高效摄取具有良好生物相容性的超微介孔氧化硅纳米颗粒

采用扫描电子显微镜(SEM)和激光共聚焦显微镜(LSCM)系统研究了超微介孔氧化硅纳米颗粒(MSNs)和杂交鹅掌楸悬浮细胞共孵育的互作特征.将MSNs通过异硫氰酸荧光素(FITC)标记后,再利用LSCM观察其被植物细胞摄取的情况.结果表明,5~15nm的MSNs可以通过内吞途径有效将FITC分子载入完整植物细胞.然而,在无MSNs作为载体的情况下,游离FITC分子则无法进入完整植物细胞.SEM观察结果进一步表明,MSNs容易聚集在完整植物细胞的表面,而且通过硅元素含量对比分析,直接证明了MSNs可以被完整植物细胞摄取到其内部.其次,利用荧光素二乙酸酯染料分析和MSNs共培养24h后的植物细胞的活性,其结果表明,这些细胞仍然保持很好的活力,而且也没有观察到明显的细胞死亡.最后发现,这些和MSNs共培养后的鹅掌楸细胞仍可以通过胚胎发育实现植株再生.综上所述,在植物生物学中,这种超微MSNs作为纳米载体可以应用到细胞的体外外源基因转染.     

新型纳米靶向给药系统载体材料的设计

新型纳米靶向给药系统的研究与开发对于难治愈性疾病（尤其是肿瘤）的治疗具有重大意义,而其发展很大程度上取决于载体材料 的设计。构思巧妙、设计合理的载体材料能使载体实现靶向功能,将药物定位浓集于病灶部位,并最大限度地发挥高效低毒的作用。基于 不同的靶向策略,包括被动靶向、主动靶向和响应肿瘤微环境的靶向,综述了近年来一些新型纳米载体材料的设计,为新型纳米靶向给药 系统的研究提供参考。     

纳米盘技术在临床医学领域研究新进展

膜蛋白功能广泛,参与多种细胞活动,如细胞增殖分化、信号转导、物质运输等,近年来一直是生物医学领域研究热点之一.膜蛋白天然构象的稳定是维持其生物活性的关键因素,新型纳米材料纳米盘技术采用两亲膜支架蛋白在水相中稳定磷脂分子,进而自组装形成类似于天然磷脂双分子膜环境的盘状结构,为膜蛋白的研究提供了理想平台.与传统拟膜技术相比,纳米盘具有可溶性强、稳定性佳、尺寸可控、生物相容性高、半衰期长等优点,同时可精准设计选择性靶向,应用优势巨大.本文介绍了纳米盘技术在膜蛋白结构与功能研究中的应用,并重点综述了其在临床医学领域中的研究新进展,包括纳米盘作为疏水性药物、抗肿瘤靶向治疗药物的运输载体,具有高载药率、药物可控释、靶向功能的运载能力;作为小分子蛋白的拟膜环境对目标蛋白的亲和固定性和作为高密度脂蛋白的有效补充在心血管疾病中清除胆固醇的高效性和可控性.综上,纳米盘技术能够为未来膜蛋白相关研究以及其他临床疾病的诊断与治疗提供新方法与新思路.     

Mesoporous silica nanoparticles in nanotechnology

Mesoporous silica nanoparticles (MSNs) are a versatile drug delivery system that can be used for loading of different guest molecules such as peptides, proteins, anticancer agents, and genetic material. MSNs are considered promising drug carriers due to their tuneable particle size, pore structure, and surface functionalization. Thus, MSNs provide opportunities for their effective application in a wide variety of fields. In the current review, we discuss both conventional and advanced MSNs synthesis methods, including their applications for drug delivery, gatekeepers, and biosensors. In addition, the research progress in biocompatibility, cytotoxicity, and internalization mechanisms is reported.     

Development of Duloxetine Hydrochloride Loaded Mesoporous Silica Nanoparticles: Characterizations and In Vitro Evaluation

This study investigated the potential use of mesoporous silica nanoparticles (MSNs) as a carrier for duloxetine hydrochloride (DX), which is prone to acid degradation. Sol–gel and solvothermal methods were used to synthesize the MSNs, which, after calcination and drug loading, were then characterized using X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) technique, thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and diffuse reflectance ultraviolet-visible (DRS-UV-Vis) spectroscopy. Releases of DX from the MSNs were good in pH 7.4 (90%) phosphate buffer but poor in acidic pH (40%). In a comparative release study between the MSNs in phosphate buffer, TW60-3DX showed sustained release for 140 h, which was higher than the other nanoparticles. The mechanism of DX release from the MSNs was studied using Peppas kinetics model. The “n” value of all three MSNs ranged from 0.45 to 1 with a correlation coefficient (r²) >0.9, which indicated that the release of the drug from the system follows the anomalous transport or non-Fickian diffusion. The results supported the efficacy of mesoporous silica nanoparticles synthesized here as a promising carrier for duloxetine hydrochloride with higher drug loading and greater pH-sensitive release.

Electronic supplementary material

The online version of this article (doi:10.1208/s12249-014-0273-x) contains supplementary material, which is available to authorized users.KEY WORDS: controlled release, duloxetine hydrochloride, meso silica nanoparticles, sol–gel synthesis     

The Practicality of Mesoporous Silica Nanoparticles as Drug Delivery Devices and Progress Toward This Goal

Mesoporous silica nanoparticles (MSNs) have been proposed as drug delivery devices for approximately 15 years. The history of in vitro studies has been promising, demonstrating that MSNs have the capability for stimulus-responsive controlled release, good cellular uptake, cell specific targeting, and the ability to carry a variety of cargoes from hydrophobic drug molecules to imaging agents. However, the translation of the in vitro findings to in vivo conditions has been slow. Herein, we review the current state-of-the-art in the use of MSN for systemic drug delivery in vivo and provide critical insight into the future of MSNs as systemic drug delivery devices and directions that should be undertaken to improve their practicality.     

The Serum-Resistant Transfection Evaluation and Long-Term Stability of Gene Delivery Dry Powder Based on Mesoporous Silica Nanoparticles and Polyethyleneimine by Freezing-Drying

Mesoporous silica nanoparticles (MSNs) with large surface area, tunable pore size, and low toxicity can act as suitable vehicles for drug and gene delivery. An MSN/DNA/PEI complex delivery system was prepared by using MSNs to hold plasmid DNA coated with polyethyleneimine (PEI), and the dry powder formulation was produced by freeze-drying with trehalose as lyoprotectant. The MSN/DNA/PEI complexes successfully enhanced the gene expression with about 1.5-fold higher efficiency as compared with the control, and even better effects and lower toxicity were achieved at lower content of PEI. Also, this gene delivery system showed nearly sixfold higher efficiency in the serum-containing condition than the control, so further application of these vehicles in vivo is highly appreciated. Besides, the trehalose containing lyophilized formulation could hold the availability for at least 4 months of storing at room temperature, presenting the potential for industrial production and transportation of gene therapy.     

Mesoporous silica nanoparticles as a carrier platform for intracellular delivery of nucleic acids

Virus-mediated gene delivery has been, to date, the most successful and efficient method for gene therapy. However, this method has been challenged because of serious safety concerns. Over the past decade, mesoporous silica nanoparticles (MSNs) have attracted much attention for intracellular delivery of nucleic acids. Delivery of cellular plasmid DNA (pDNA) is designed to replace the function of a defective gene and restore its normal function in the cell. Delivery of small interfering RNAs (siRNAs) can selectively knockdown genes by targeting specific mRNAs. The biocompatibility and unique structures of MSNs make these nanoparticles ideal candidates to act as biomolecule carriers. This concise review highlights current progress in the field of nucleic acid delivery using MSNs, specifically for delivery of pDNA, siRNA, and combinatorial delivery of nucleic acids and drugs. The review describes important design parameters presently being applied to MSNs to administer drugs and therapeutic nucleic acids.     

Recent patents on the synthesis and application of silica nanoparticles for drug delivery

Drug delivery systems are designed to improve therapy efficacy as well as patient compliance. This could be accomplished by specifically targeting a medication intact to its active site, therefore reducing side-effects and enabling high local drug concentrations. Silica nanoparticles have gained ground in the biomedical field for their biocompatibility and biodegradability, being themselves inert and stable, thus enabling a variety of formulation designs for application in the pharmaceutical industry. This paper is a review of the recent patents on the applications of silica nanoparticles for drug delivery and their preparation. The review will focus on the different techniques available to obtain silica nanoparticles with variable morphology and their drug targeting applications, providing an overview of silica particles synthesis described in the literature.     

Enriched Au nanoclusters with mesoporous silica nanoparticles for improved fluorescence/computed tomography dual‐modal imaging

ObjectivesAu nanoclusters (AuNCs) have been used widely in fluorescence bio‐imaging because of their good fluorescence, small particle size and non‐cytotoxicity. AuNCs are also efficient in computed tomography (CT) imaging. Hence, a dual‐modal imaging probe can be constructed without any complicated modification processes by exploiting the excellent performance of AuNCs. In the present study, AuNCs were enriched with mesoporous silica nanoparticles (MSNs) to obtain enhanced fluorescence/CT dual‐modal imaging, which was capable of acquiring more imaging information for diseases compared with single‐mode imaging.Materials and methodsBiocompatible bovine serum albumin (BSA)‐capped AuNCs were prepared and loaded into amine‐functionalized MSNs to form MSN@AuNCs. BSA‐AuNCs, MSNs, and MSN@AuNCs were characterized by ultraviolet‐visible (UV‐vis) spectra, transmission electron microscopy (TEM), fluorescence spectra, and zeta potential. CT imaging was recorded using micro‐CT scanning. Fluorescence imaging was measured using confocal laser scanning microscopy and flow cytometry.ResultsThe prepared AuNCs and MSNs possessed good properties as previously reported. The fluorescence intensity and CT value of the AuNCs were enhanced after being enriched with MSNs. The nanoparticles were both non‐cytotoxic. Confocal laser scanning microscopy and flow cytometry indicated that MSN@AuNCs in CAL‐27 cells showed improved fluorescence imaging compared with simple AuNCs at the same concentration.ConclusionsThe results revealed that the strategy of enriching AuNCs with MSNs can obtain highly sensitive fluorescence/CT dual‐modal imaging, which indicated the potential of this nanoparticle in the diagnosis and treatment of disease.     

细胞膜仿生修饰纳米粒肿瘤治疗的研究进展

大量研究证明,细胞膜仿生修饰通过将不同细胞膜包被于纳米粒表面,赋予纳米粒新的生物学功能.纳米粒被细胞膜仿生修饰后,获得了细胞膜表面丰富的蛋白质并保留了纳米粒的高载药能力,延长体内循环时间,使纳米粒具有逃避免疫系统,跨越各种生理屏障的能力.本文总结了近年来细胞膜仿生修饰纳米粒用于肿瘤治疗的最新进展,讨论了细胞膜仿生修饰纳...     

Stabilization of RNA through Absorption by Functionalized Mesoporous Silicate Nanospheres

The potential for encapsulating RNA within tunable, semi-permeable structures for storage and transportation purposes offers an interesting approach to the reduction of stringent storage requirements that often hamper the field application of genetic analysis methods. In this study, we assessed the potential for application of functionalized, porous silicate sorbents in maintaining nucleic acid integrity. Mesoporous silica nanoparticles (MSNs) with and without incorporated stabilizing reagents were used to encapsulate triosephosphate isomerase mRNA of Arabidopsis thaliana. The absorption, elution, and the long-term stability of the RNA were monitored by using quantitative real-time RT-PCR. The results indicate that adsorbed RNA can be eluted from the sorbents using simple buffers and employed directly for downstream molecular diagnostic assays without any further processing. RNA integrity can be maintained for extended time periods under refrigeration temperatures in the presence of covalently immobilized stabilizing compounds. This study provides initial evidence of the potential for application of MSNs in transportation and storage. They may also have utility in sample collection and processing in restrictive environments.