纳米基因载体在生物医学中的研究进展

纳米生物技术是21世纪具有开发前景的科技领域,纳米材料的出现为解决基因转移载体提供了新的思路,本文在阐述纳米基因载体的优势、种类及导入体内方法的基础上,综述了纳米基因载体在基因治疗、遗传育种等生物医学上的应用.     

基因治疗研究中脂质体介导的基因转移技术

对于脂质体的深入研究特别是阳离子脂质体的研制使其逐步成为重要的基因转移载体之一,并且初步应用于基因治疗研究,同时多种靶向脂质体的研制也为体内靶向基因转移和表达奠定了基础。本文就脂质体的结构、功能、在基因治疗研究中的应用以及各种靶向脂质体的研制进行了介绍。     

纳米粒子在CRISPR/Cas9基因治疗中的应用

CRISPR/Cas9基因编辑技术已成为基因治疗领域最有前景的工具。在临床应用中,对CRISPR/Cas9进行安全有效的递送一直是亟待解决的问题。纳米粒子,如脂基纳米粒子、聚合物纳米粒子、纳米金颗粒以及生物膜类纳米粒子等,因其生物相容性、安全性和可设计性等特点有望为基因治疗带来新的突破。文中首先对纳米粒子的特性和基因治疗中CRISPR/Cas9的发展进行了概述,然后详细归纳了纳米粒子在递送不同形式的CRISPR/Cas9中的应用,最后对纳米粒子介导的基因治疗的递送在未来面临的挑战和安全性等方面作出总结论述。     

无机纳米粒子作为基因载体的研究进展

转染是将具生物功能的核酸转移、运送到细胞内,并使其在细胞内维持生物功能的过程。作为现代生物化学和分子生物学中的一种主要技术手段,转染对于基因治疗有重要的意义。无机纳米粒子作为基因载体受到人们日益广泛的关注,其具有易于制备,可进行多样化的表面修饰等多种优势。本文将概述无机纳米粒子作为基因载体的现状及其对基因表达的影响。     

纳米基因载体在生物医学中的研究进展

纳米生物技术是21世纪具有开发前景的科技领域,纳米材料的出现为解决基因转移载体提供了新的思路,本文在阐述纳米基因载体的优势、种类及导入体内方法的基础上,综述了纳米基因载体在基因治疗、遗传育种等生物医学上的应用。     

基因治疗心肌缺血的载体应用新进展

近年来,随着基因治疗技术的不断进步,为心肌缺血的治疗开辟了一条全新的途径,并取得了一些令人鼓舞的进展。基因治疗主要包括治疗基因、基因转移载体以及基因导入途径三个方面。基因转移载体又在治疗基因和基因表达之间起着桥梁作用,因此,发展安全、高效的基因转移系统是基因治疗的关键之一。目前用于基因治疗心肌缺血基因转移的载体主要有病毒载体和非病毒载体。下面将就不同载体在心肌缺血的基因治疗中的应用进展进行简要的总结。     

基因治疗心肌缺血的载体应用新进展

近年来,随着基因治疗技术的不断进步,为心肌缺血的治疗开辟了一条全新的途径,并取得了一些令人鼓舞的进展。基因治疗主要包括治疗基因、基因转移载体以及基因导入途径三个方面。基因转移载体又在治疗基因和基因表达之间起着桥梁作用,因此,发展安全、高效的基因转移系统是基因治疗的关键之一。目前用于基因治疗心肌缺血基因转移的载体主要有病毒载体和非病毒载体。下面将就不同载体在心肌缺血的基因治疗中的应用进展进行简要的总结。     

基因治疗载体及其基因转移技术的关键问题与研究现状

目前使用的基因治疗载体及其基因转移技术中还没有一种能用于临床并永久有效的基因转移技术 .该文分析了直接体内转移、间接体内转移及其非载体法、病毒载体法、非病毒性生物载体法等基因治疗转移技术存在的一些关键问题 ,并探讨了各问题的解决办法或研究策略以及基因治疗载体研究的发展方向     

多功能信封式纳米载体研究进展

基因治疗成功的关键技术之一是研制出安全高效的基因转染载体。多功能信封式纳米载体具有易进入细胞、低毒性、低免疫原性、低致瘤性、易制备、转染效率高等优点,是一种有良好应用前景的基因转染载体。综述了近年来多功能信封式纳米载体的研究进展。     

不同修饰对壳聚糖转基因效果的影响

目的:探讨不同修饰的壳聚糖包裹的质粒(Chi-DNA)纳米复合物在口服发送中外源 基因在消化道中的表达差异.方法:分别使用明胶、海藻酸钠、PEG及乙酰化修饰包裹含Lac Z的质粒pCMVa的壳聚糖纳米颗粒,通过口服发送后经X-gal染色检测目的基因在小鼠体内的 表达.结果:修饰后的Chi-DNA纳米复合物都能抵抗胃酸的降解0.5h以上 ,其中PEG及乙酰化 修饰的Chi-DNA纳米复合物在胃酸处理1h时仍有部分残留.X-gal染色显示,修饰后的Chi-DN A纳米复合物都有a半乳糖苷酶的表达,其中PEG、海藻酸钠修饰的Chi-DNA纳米复合物在鼠 胃和小肠中表达量最高.结论:PEG、海藻酸钠修饰的Chi-DNA纳米复合物有望成为高效的基因治疗用非病毒口服发送系统.     

Nanoparticulate systems for polynucleotide delivery

Nanotechnology has tremendously influenced gene therapy research in recent years. Nanometer-size systems have been extensively investigated for delivering genes at both local and systemic levels. These systems offer several advantages in terms of tissue penetrability, cellular uptake, systemic circulation, and cell targeting as compared to larger systems. They can protect the polynucleotide from a variety of degradative and destabilizing factors and enhance delivery efficiency to the cells. A variety of polymeric and non-polymeric nanoparticles have been investigated in an effort to maximize the delivery efficiency while minimizing the toxic effects. This article provides a review on the most commonly used nanoparticulate systems for gene delivery. We have discussed frequently used polymers, such as, polyethyleneimine, poly (lactide-co-glycolide), chitosan, as well as non-polymeric materials such as cationic lipids and metallic nanoparticles. The advantages and limitations of each system have been elaborated.     

Virus‐inspired and mimetic designs in non‐viral gene delivery

Virus‐inspired mimics for nucleic acid transportation have attracted much attention in the past decade, especially the derivative microenvironment stimuli‐responsive designs. In the present mini‐review, the smart designs of gene carriers that overcome biological barriers and realize an efficient delivery are categorized with respect to the different “triggers” provided by tumor cells, including pH, redox potentials, ATP, enzymes and reactive oxygen species. Some dual/multi‐responsive gene vectors have also been introduced that show a more precise and efficient delivery in the complicated environment of human body. In addition, inspired by the special recognition mechanisms and components of viruses, improvements in the design of carriers relating to targeting/penetration properties, as well as chemical component evolution, are also addressed.     

Organic/inorganic nanohybrids as multifunctional gene delivery systems

In this review, we summarize the rational design and versatile application of organic/inorganic hybrid gene carriers as multifunctional delivery systems. Organic/inorganic nanohybrids with both organic and inorganic components in one nanoparticle have attracted intense attention because of their favorable properties. Particularly, nanohybrids comprising cationic polymers and inorganic nanoparticles are considered to be promising candidates as multifunctional gene delivery systems. In this review, we begin with an introduction of gene delivery and gene carriers to demonstrate the incentive for fabricating nanohybrids as multifunctional carriers. Next, the construction strategies and morphology effects of organic/inorganic hybrid gene carriers are summarized and discussed. Both sections provide valuable information for the design and synthesis of hybrid gene carriers with superior properties. Finally, an overview is provided of the application of nanohybrids as multifunctional gene carriers. Diverse therapies and versatile imaging‐guided therapies have been achieved via the rational design of nanohybrids. In addition to a simple combination of the functions of organic and inorganic components, the performances arising from the synergistic effects of both components are considered to be more intriguing. In summary, this review might offer guidance for the understanding of organic/inorganic nanohybrids as multifunctional gene delivery systems.     

Tumor microenvironment as the “regulator” and “target” for gene therapy

In this review, we focus on strategies for designing functional nano gene carriers, as well as choosing therapeutic genes targeting the tumor microenvironment. Gene mutations have a great impact on the occurrence of cancer. Thus, gene therapy plays a major role in cancer therapy and has the potential to cure cancer. Well‐designed gene therapy largely relies on effective gene carriers, which can be divided into viral carriers and non‐viral carriers. A gene carrier delivers functional genes to their intracellular target and avoids nucleic acids being degraded by nucleases in the serum. Most conventional cancer gene therapies only target cancer cells and do not appear to be sufficintly efficient to pass clinical trials. Accumulating evidence has shown that extending the therapeutic strategies to the tumor microenvironment, rather than the tumor cell itself, can allow more options for achieving robust anti‐cancer efficiency. In addition, unusual features between tumor microenvironment and normal tissues, such as a lower pH, higher glutathione and reactive oxygen species concentrations, and overexpression of some enzymes, facilitate the design of smart stimuli‐responsive gene carriers regulated by the tumor microenvironment. These carriers interact with nucleic acids and then form stable nanoparticles under physiological conditions. By regulation of the tumor microenvironment, stimuli‐responsive gene carriers are able to change their properties and achieve high gene delivery efficiency. Considering the tumor microenvironment as the “regulator” and “target” when designing gene carriers and choosing therapeutic genes shows significant benefit with respect to improving the accuracy and efficiency of cancer gene therapy.     

Nanoparticulate system for efficient gene transfer into refractory cell targets

A biocompatible, nanoparticulate formulation has been designed to retain, protect, and deliver adenoviral gene constructs over an extended time course. Such devices can be administered locally or systemically with low toxicity. A multipolymeric nanoparticulate system, featuring very high stability in physiologic media, was designed to allow efficient in vitro gene transfer. The efficacy of nanoparticulate delivery is effective in cell systems that are normally refractory to gene transfer, such as pancreatic islets and antigen-presenting cells. The findings suggest a nonspecific uptake system that permits adenoviral particle release within the transfected cells. A comparison with literature data revealed that our system is efficient at much lower levels (at least three orders of magnitude) of infectious viral particles.     

Targeting of nanoparticles to the clathrin-mediated endocytic pathway

Nanoparticles (NPs) are considered attractive carriers for gene therapy and drug delivery owing to their minor toxic effect and their ability to associate and internalize into mammalian cells. In this study, we compared the endocytosis into HeLa cells of NPs exposing either a negative or positive charge on their surface. The exposed charge significantly affected their ability to internalize as well as the cellular endocytosis mechanism utilized. Negatively charged NPs show an inferior rate of endocytosis and do not utilize the clathrin-mediated endocytosis pathway. On the other hand, positively charged NPs internalize rapidly via the clathrin-mediated pathway. When this pathway is blocked, NPs activate a compensatory endocytosis pathway that results in even higher accumulation of NPs. Overall, the addition of a positive charge to NPs may improve their potential as nanoparticulate carriers for drug delivery.     

Cell-penetrating peptides: breaking through to the other side

Cell-penetrating peptides (CPPs) have been previously shown to be powerful transport vector tools for the intracellular delivery of a large variety of cargoes through the cell membrane. Intracellular delivery of plasmid DNA (pDNA), oligonucleotides, small interfering RNAs (siRNAs), proteins and peptides, contrast agents, drugs, as well as various nanoparticulate pharmaceutical carriers (e.g., liposomes, micelles) has been demonstrated both in vitro and in vivo. This review focuses on the peptide-based strategy for intracellular delivery of CPP-modified nanocarriers to deliver small molecule drugs or DNA. In addition, we discuss the rationales for the design of 'smart' pharmaceutical nanocarriers in which the cell-penetrating properties are hidden until triggered by exposure to appropriate environmental conditions (e.g., a particular pH, temperature, or enzyme level), applied local microwave, ultrasound, or radiofrequency radiation.     

Interaction of nanoparticles and cell-penetrating peptides with skin for transdermal drug delivery

Abstract

Topical or transdermal drug delivery is challenging because the skin acts as a natural and protective barrier. Therefore, several methods have been examined to increase the permeation of therapeutic molecules into and through the skin. One approach is to use the nanoparticulate delivery system. Starting with liposomes and other vesicular systems, several other types of nanosized drug carriers have been developed such as solid lipid nanoparticles, nanostructured lipid carriers, polymer-based nanoparticles and magnetic nanoparticles for dermatological applications. This review article discusses how different particulate systems can interact and penetrate into the skin barrier. In this review, the effectiveness of nanoparticles, as well as possible mode of actions of nanoparticles, is presented. In addition to nanoparticles, cell-penetrating peptide (CPP)-mediated drug delivery into the skin and the possible mechanism of CPP-derived delivery into the skin is discussed. Lastly, the effectiveness and possible mechanism of CPP-modified nanocarriers into the skin are addressed.     

Interaction of nanoparticles and cell-penetrating peptides with skin for transdermal drug delivery

Topical or transdermal drug delivery is challenging because the skin acts as a natural and protective barrier. Therefore, several methods have been examined to increase the permeation of therapeutic molecules into and through the skin. One approach is to use the nanoparticulate delivery system. Starting with liposomes and other vesicular systems, several other types of nanosized drug carriers have been developed such as solid lipid nanoparticles, nanostructured lipid carriers, polymer-based nanoparticles and magnetic nanoparticles for dermatological applications. This review article discusses how different particulate systems can interact and penetrate into the skin barrier. In this review, the effectiveness of nanoparticles, as well as possible mode of actions of nanoparticles, is presented. In addition to nanoparticles, cell-penetrating peptide (CPP)-mediated drug delivery into the skin and the possible mechanism of CPP-derived delivery into the skin is discussed. Lastly, the effectiveness and possible mechanism of CPP-modified nanocarriers into the skin are addressed.     

Cell penetrating peptide-modified pharmaceutical nanocarriers for intracellular drug and gene delivery

Cell-penetrating peptides (CPPs) including TAT peptide (TATp) have been successfully used for intracellular delivery of a broad variety of cargos including various nanoparticulate pharmaceutical carriers (liposomes, micelles, nanoparticles). Here, we will consider the main results in this area, with a special emphasis on TATp-mediated delivery of liposomes and DNA. We will also address the development of "smart" stimuli-sensitive nanocarriers, where cell-penetrating function can be activated by the decreased pH only inside the biological target minimizing thus the interaction of drug-loaded nanocarriers with nontarget cells.