纳米金的表面修饰及其在抗肿瘤中的应用

近年来,纳米金因其独特的物理化学性质在肿瘤治疗领域受到广泛重视。纳米金表面具有易修饰性,可通过化学键或非化学键引入多种基团或小分子化合物。对纳米金表面的多样化修饰可使其具有多种功能,常见的有靶向修饰、控释修饰等。越来越多的研究表明纳米金可应用于抗肿瘤诊断和治疗。经表面修饰的纳米金可用于药物的递送,放射增敏,CT成像等。文章将对纳米金的特性,纳米金表面修饰及其在肿瘤治疗中的应用等方面做以综述。     

pH敏感型纳米递药系统在肿瘤靶向治疗中的作用

目的 综述目前pH敏感纳米递药系统用于肿瘤靶向治疗中的国内外研究进展。方法 在Pubmed和Google上检索近年国内外资料,阐明pH敏感纳米递药系统靶向肿瘤治疗的作用机制,对超顺磁性纳米粒、胶束、树状大分子等相关研究成果进行总结和评价。结果 传统肿瘤化疗药物普遍存在疗效低、副作用大等问题,而近年来研发的pH响应的纳米载体可通过EPR效应积聚于肿瘤组织,并在弱酸性的肿瘤细胞外液或经内吞作用后在细胞质或溶酶体中释放药物。该pH敏感型载体能促进药物的靶向递送,在减少系统性副作用的同时提高肿瘤化疗疗效。结论 pH敏感纳米递药系统在肿瘤靶向治疗中具有广阔的应用前景,开发具有靶向性、高效性、安全性的递药系统是目前该领域研究主要方向之一。     

细胞膜仿生递药系统在肿瘤治疗中的研究进展

纳米药物递送系统在肿瘤精准医疗领域具有良好的应用前景,但有机或无机合成的纳米材料存在制备过程繁琐和易被机体内免疫系统识别、清除等问题。受自然界生物系统的启发,生物细胞膜介导的仿生纳米递药系统近年来成为研究热点。生物膜仿生递药系统通过机体内源性细胞膜对纳米载体表面进行包覆修饰,有效地将天然生物膜“自体”性质和“人工”功能载体的优势相融合,赋予其肿瘤靶向性,低免疫原性和血液长循环等特点。基于纳米药物和细胞膜仿生技术在肿瘤精准医疗领域的研究进展,对细胞膜仿生修饰纳米粒的实验基础、膜仿生纳米递药系统的构建及在肿瘤靶向化疗、免疫治疗、光热治疗上的应用三方面进行综述,并对未来研究进行展望。     

纳米载体逆转肿瘤多药耐药机制的研究进展

肿瘤多药耐药（multidrug resistance,MDR）是导致肿瘤化疗失败、影响治疗效果的主要原因之一。随着生物技术的快速发展,纳米载体在逆转MDR方面呈现出增强药物靶向性、减少药物外排、降低药物毒副作用等明显优势,受到国内外学者的广泛关注。本文就肿瘤MDR发生机制和纳米载体逆转MDR方面的研究成果作一综述。     

叶酸受体介导的肿瘤靶向纳米递药系统

叶酸受体在上皮源性的恶性肿瘤细胞膜表面高度表达。叶酸靶向纳米递药系统具有叶酸-叶酸受体主动靶向和纳米递药系统被动靶向的双重优势,可实现化疗药物对肿瘤组织的靶向递送,有效提高药物疗效,减少毒副作用。本文就近年来研究较多的叶酸-脂质体、叶酸-树枝状聚合物、叶酸-聚合物胶束、叶酸-纳米球等叶酸受体介导的肿瘤靶向递药系统进行综述。     

纳米磁靶向药物载体在肿瘤治疗中的研究进展

纳米磁靶向药物载体是靶向治疗的一种载体形式,粒径在1~1000nm之间,它借助于磁场使药物载体聚集在靶部位,平稳释放药物,提高靶部位药物浓度,增强治疗效果,同时减少其它部位的药物分布,降低药物的毒副作用。该药物载体一方面具有磁靶向药物载体的一般特性,结合固定磁场或交变磁场而具有靶向性或产热性,携带化疗药物或放射性物质,能杀灭肿瘤细胞;另一方面粒径达到纳米级,并具有体内长循环等特性。本文介绍纳米磁靶向药物载体在肿瘤治疗(包括化疗、放疗、热疗等)领域的研究进展。1纳米磁靶向药物载体在肿瘤化疗中的应用纳米磁靶向药物载体能携…     

温敏聚合物自组装纳米粒子在抗肿瘤药物递送中的应用

作为抗肿瘤治疗的主要手段,化疗最大的缺陷在于化疗药物缺乏肿瘤靶向性,易对正常组织产生高毒性,并导致治疗效果不理想。为了解决这一问题,越来越多的聚合物纳米载体被用于递送抗肿瘤药物,包括对温度刺激能作出响应的温敏聚合物自组装纳米载体。笔者综述了近年来温敏聚合物自组装载体及其纳米粒子的研究进展,并介绍了其在抗肿瘤药物递送中的应用。     

磁性药物载体在抗肿瘤方面的研究进展

通过外加磁场的引导作用,使负载抗癌药物的磁性载体靶向定位于靶区,提高靶组织的药物浓度,有效降低药物对正常组织或细胞的毒副作用及其他不良反应。磁性药物载体还具有靶向性、缓释、控释等优点,已成为了肿瘤靶向治疗常用的新型载体系统。本文综述了磁性药物载体磁性纳米颗粒、磁性脂质体、磁性微球在肿瘤治疗与诊断中的应用进展。     

肿瘤治疗的细胞药物递送系统的研究进展

目前,肿瘤的临床治疗主要以手术、化疗和放射疗法为主,但仍存在复发和不良反应明显等问题。细胞药物递送系统不仅可以避免纳米颗粒药物的毒性,又可以增加药物的生物利用度,提高生物相容性、靶向性。总结了活细胞、死细胞、外泌体及其药物递送系统的载药特点和在肿瘤治疗中的应用,为肿瘤治疗提供了更多的治疗手段。     

基于纳米热疗剂的肿瘤热化疗研究进展

鉴于热疗可以显著增加化疗药物的细胞毒性,因此将化疗与热疗联合使用,即热化疗,可以使化疗药物在较低浓度下达到较好的治疗效果.但是提高临床热化疗疗效的关键是实现对肿瘤部位的靶向性加热.为克服传统全身性热疗靶向性不足的缺陷,具有极高光热/磁热转化能力的纳米热疗剂已经成为目前相关领域的研究重点.特别是通过纳米热疗剂与化疗药物的共载,实现热疗和化疗的高效协同作用,已经成为目前肿瘤靶向性热化疗的研究热点.     

Micelles and nanoparticles for ultrasonic drug and gene delivery

Drug delivery research employing micelles and nanoparticles has expanded in recent years. Of particular interest is the use of these nanovehicles that deliver high concentrations of cytotoxic drugs to diseased tissues selectively, thus reducing the agent's side effects on the rest of the body. Ultrasound, traditionally used in diagnostic medicine, is finding a place in drug delivery in connection with these nanoparticles. In addition to their non-invasive nature and the fact that they can be focused on targeted tissues, acoustic waves have been credited with releasing pharmacological agents from nanocarriers, as well as rendering cell membranes more permeable. In this article, we summarize new technologies that combine the use of nanoparticles with acoustic power both in drug and gene delivery. Ultrasonic drug delivery from micelles usually employs polyether block copolymers and has been found effective in vivo for treating tumors. Ultrasound releases drug from micelles, most probably via shear stress and shock waves from the collapse of cavitation bubbles. Liquid emulsions and solid nanoparticles are used with ultrasound to deliver genes in vitro and in vivo. The small packaging allows nanoparticles to extravasate into tumor tissues. Ultrasonic drug and gene delivery from nanocarriers has tremendous potential because of the wide variety of drugs and genes that could be delivered to targeted tissues by fairly non-invasive means.     

Dual Responsive Hybrid Nanoparticle for Tumor Chemotherapy Combined with Photothermal Therapy

With the deepening of tumor targeting research, the application of intelligent responsive drug carriers in the field of controlled drug release has become more and more extensive, and multiple responsive nano drug carriers have attracted greater attention. In this paper, nanoparticles with gold nanorods (GNR) as the core, mesoporous silica (mSiO₂) doped with hydroxyapatite (HAP) as the inorganic hybrid shell and physically loaded with doxorubicin hydrochloride (DOX·HCl) are prepared (DOX/GNR/mSiO₂/HAP, DNPs). DNPs nanoparticles have a typical core-shell structure. The gold nanorods as the core have extremely high light-to-heat conversion efficiency. Under the irradiation of near-infrared light, light can be converted into heat. The inorganic hybrid shell is a drug reservoir. The excellent photothermal response of gold nanorods combined with the excellent pH response of hydroxyapatite can obtain slow and sustained release of chemotherapeutic drugs. In vivo and in vitro anti-tumor cell activity study show that the DNPs in the laser showed stronger cytotoxicity than the other groups. Compared to chemotherapy and phototherapy alone, DNPs selectively accumulate in the tumor through the enhanced penetration and retention (EPR) effects. and have the unified function of hyperthermia and chemotherapy, and have significant inhibitory effect on tumor growth. Therefore, this study provides a new idea for the study of the combination of multiple therapeutic methods in the treatment of cancer.     

Nanomedicines for ocular NSAIDs: safety on drug delivery

The eyes are among the most readily accessible organs in terms of location in the body, yet drug delivery to eye tissues is particularly problematic. Poor bioavailability of drugs from ocular dosage forms is mainly due to precorneal loss factors (e.g., tear dynamics, nonproductive absorption, transient residence time in the cul-de-sac, and relative impermeability of the corneal epithelial membrane). There is a clear need for effective topical formulations capable of promoting drug penetration and maintaining therapeutic levels with a reasonable frequency of application—a strategy that can also result in enhancement of side effects that probably would not be acceptable. Delivery of a drug via a nanotechnology-based product fulfills three main objectives: enhancement of drug permeation, controlled release, and targeting. The inflammatory response of the ocular tissues is a common side effect associated with ophthalmic surgery. Together with steroidal agents, nonsteroidal anti-inflammatory drugs are used in eye surgery. In this review we focus on microemulsions, polymeric nanoparticles, liposomes, solid lipid nanoparticles, and drug nanocrystals as formulations incorporating anti-inflammatory drugs for ophthalmic application.From the Clinical EditorThis review focuses on microemulsions, polymeric nanoparticles, liposomes, solid lipid nanoparticles, and drug nanocrystals as novel high efficiency delivery systems of anti-inflammatory drugs in ophthalmic applications.     

载药金纳米粒的研究进展

近年来,作为一种新型药物递送系统,金纳米粒已引起了广泛关注。由于其特殊的物理化学性质,能与多种类型药物发生相互作用,如蛋白质、核酸、小分子药物等,从而可应用于肿瘤治疗和检测。笔者对载药金纳米粒的制备方法、载药方式和安全性等问题进行综述。     

Nanoparticles as drug delivery systems

Controlled drug delivery systems (DDS) have several advantages compared to the traditional forms of drugs. A drug is transported to the place of action, hence, its influence on vital tissues and undesirable side effects can be minimized. Accumulation of therapeutic compounds in the target site increases and, consequently, the required doses of drugs are lower. This modern form of therapy is especially important when there is a discrepancy between the dose or the concentration of a drug and its therapeutic results or toxic effects. Cell-specific targeting can be accomplished by attaching drugs to specially designed carriers. Various nanostructures, including liposomes, polymers, dendrimers, silicon or carbon materials, and magnetic nanoparticles, have been tested as carriers in drug delivery systems. In this review, the aforementioned nanocarriers and their connections with drugs are analyzed. Special attention is paid to the functionalization of magnetic nanoparticles as carriers in DDS. Then, the advantages and disadvantages of using magnetic nanoparticles as DDS are discussed.     

Inorganic nanoparticles for hydrophobic anticancer drug delivery

OBJECTIVE Many drug candidates identified from natural products are poorly water-soluble.The surfactants used to disperse the hydrophobic anticancer drugs in water may cause a serious of acute hypersensitivity reactions.Nanotechnology provides an alternative strategy for delivery of anticancer drugs.In the present study,different inorganic nanoparticles are utilized as hydrophobic anticancer drug carriers.METHODS Different inorganic superparamagnetic iron oxide,platinum and gold nanoparticles were synthesized.The hydrophobic anticancer drugs such as curcumin,gambogic acid and doxorubicin(DOX)base were loaded into the porous area or onto the surface of the nanoparticles.Cellular uptake and biocompatibility of nanoparticles were studied in human glioblastoma U-87 MG cells.The anticancer effect of drug loaded nanoparticles was compared with that of free drugs.Photothermal conversion of platinum and gold nanoparticles was studied by irradiation of nanoparticles with a near-infrared laser.RESULTS The synthesized nanoparticles are readily internalized by U-87 MG cells,and the internalized nanoparticles are mainly localized in endosomes/lysosomes in cells.The nanoparticle-based drug carrier provides the aqueous dispersions of the hydrophobic drugs.In endosomes/lysosomes mimicking buffers with a pH of 4.5-5.5,pH-dependent drug release was observed from drug loaded nanoparticles.The intracellular drug content and cytotoxicity are significantly higher for drug loaded nanoparticles than free drug.Photothermal treatment has a synergistic effect on drug′s anticancer activity.CONCLUSION These results suggested inorganic nanoparticles is a promising intracellular carrier for hydrophobic anticancer drugs.     

Somatostatin receptors as a new active targeting sites for nanoparticles

The delivery of nanoparticles through receptor-mediated cell interactions has nowadays a major attention in the area of drug targeting applications. This specific kind of targeting is mediated by localized receptors impeded into the target site with subsequent drugs internalization. Hence, this type of interaction would diminish side effects and enhance drug delivery efficacy to the target site. Somatostatin receptors (SSTRs) are one type of G protein-coupled receptors, which could be active targeted for various purposes. There are five SSTRs types (SSTR1-5) which are localized at various organs in the body and spread into different tissues. SSTRs could be considered as a promising target to various nanoparticles which is facilitated when nanoparticles are modified through specific ligand or coating to allow better binding. This review discusses the exploration of SSTRs for active targeting of nanoparticles with certain emphasize on their interaction at the cellular level.     

Enhanced permeability and retention of macromolecular drugs in solid tumors: A royal gate for targeted anticancer nanomedicines

Over the past two decades cancer has ascended the causes of human death to be number one or two in many nations world wide. A major limitation inherent to most conventional anticancer chemotherapeutic agents is their lack of tumor selectivity. One way to achieve selective drug targeting to solid tumors is to exploit abnormalities of tumor vasculature, namely, hypervascularisation; aberrant vascular architecture; extensive production of vascular permeability factors stimulating extravasation within tumor tissues; and lack of lymphatic drainage. Maeda and his colleagues have extensively studied tumor vascular abnormalities in terms of active and selective delivery of anticancer drugs to tumor tissues, notably defining the enhanced permeability and retention effect (EPR effect) of macromolecular drugs in solid tumors. Due to their large molecular size, nanosized macromolecular anticancer drugs administered intravenously (i.v.) escape renal clearance. Often they can not penetrate the tight endothelial junctions of normal blood vessels, but they can extravasate in tumour vasculature and become trapped in the tumor vicinity. With time the tumor concentration will build up reaching several folds higher than that of the plasma due to lack of efficient lymphatic drainage in solid tumor; an ideal application for EPR-based selective anticancer drug delivery. Establishing this principle hastened development of various polymer conjugates and polymeric micelles as well as multifunctional nanoparticles for targeted cancer chemotherapy. Indeed this selective high local concentration of nanosized anticancer drugs in tumor tissues has proven superior in therapeutic effect with minimal side effects in both preclinical and clinical settings.

In this review the mechanisms and factors involved in the EPR effect, as well as the uniqueness of nanoscale drugs for tumor targeting through EPR effect, will be discussed in detail.     

Lipid-based drug delivery systems for cancer treatment

It is a fact that chemotherapy agents have little specificity for cancer cells, this leading to low concentrations into the tumor interstititum and severe side effects on healthy tissues. The formulation of lipid-based nanomedicines against cancer has been hypothesized to improve drug localization into the tumor tissue and to increase the anticancer efficacy of concentional drugs, while minimizing their systemic adverse effects. In this review, special attention is devoted to the analysis of the state-of-the-art in the development of lipid-based drug carriers against cancer. Specifically, the most significant in vitro and in vivo results on the use of niosomes, liposomes, and solid lipid nanoparticles are revised. It is concluded that biodistribution profiles of chemotherapy agents can be controlled by their loading to such nanoplatforms. Lipid-based nanomedicines offer an interesting approach to the delivery of anticancer drugs to brain tumors, and to reverse multi-drug resistance of cancer cells. Finally, a deep evaluation of the applicability of drug delivery strategies in the formulation of lipid-based nanoplatforms is carried out. They involve active drug targeting (including ligand-mediated delivery, and stimuli-sensitive carriers), and passive drug targeting (through the enhanced permeability and retention effect) to tumors.     

Enhanced permeability and retention of macromolecular drugs in solid tumors: a royal gate for targeted anticancer nanomedicines

Over the past two decades cancer has ascended the causes of human death to be number one or two in many nations world wide. A major limitation inherent to most conventional anticancer chemotherapeutic agents is their lack of tumor selectivity. One way to achieve selective drug targeting to solid tumors is to exploit abnormalities of tumor vasculature, namely, hypervascularisation; aberrant vascular architecture; extensive production of vascular permeability factors stimulating extravasation within tumor tissues; and lack of lymphatic drainage. Maeda and his colleagues have extensively studied tumor vascular abnormalities in terms of active and selective delivery of anticancer drugs to tumor tissues, notably defining the enhanced permeability and retention effect (EPR effect) of macromolecular drugs in solid tumors. Due to their large molecular size, nanosized macromolecular anticancer drugs administered intravenously (i.v.) escape renal clearance. Often they can not penetrate the tight endothelial junctions of normal blood vessels, but they can extravasate in tumour vasculature and become trapped in the tumor vicinity. With time the tumor concentration will build up reaching several folds higher than that of the plasma due to lack of efficient lymphatic drainage in solid tumor; an ideal application for EPR-based selective anticancer drug delivery. Establishing this principle hastened development of various polymer conjugates and polymeric micelles as well as multifunctional nanoparticles for targeted cancer chemotherapy. Indeed this selective high local concentration of nanosized anticancer drugs in tumor tissues has proven superior in therapeutic effect with minimal side effects in both preclinical and clinical settings. In this review the mechanisms and factors involved in the EPR effect, as well as the uniqueness of nanoscale drugs for tumor targeting through EPR effect, will be discussed in detail.