主动靶向脂质体研究进展

目的 介绍主动靶向脂质体最新研究进展。方法 查阅近年来国内外相关文献,对主动靶向脂质体的表面修饰、配体选择及应用进行进行总结和归纳。结果 主动靶向脂质体的表面修饰有三种方法：作为组份直接制备;键合到脂质体表面;后插入法。主动靶向脂质体可以将药物传递到靶组织、靶向细胞或靶细胞器,提高药物的生物利用度,而不增加对正常组织或细胞的毒性,是近年研究最为广泛的主动靶向给药系统。结论 主动靶向脂质体是一种非常有前途的给药系统。     

用于抗肿瘤药物递送的脂质体表面修饰策略

脂质体作为一种传统的药物传递系统,因其在药物及蛋白质、基因、核酸等生物活性物质的高效传递方面的应用而备受研究领域的关注。脂质体给药系统在抗肿瘤药物研究领域经历了常规脂质体、长循环脂质体、配体功能脂质体、刺激响应型脂质体等4个阶段。现结合相关文献,综述了这4种脂质体给药系统常用的表面修饰靶向策略和研究进展,以期为脂质体的进一步研究和基本靶向修饰提供参考。     

受体介导脂质体的研究进展

配体修饰脂质体通过受体介导的内吞作用主动靶向药物至靶位，增加了药物靶向的特异性，减少了对非靶组织器管损伤，提高了疗效，是一种具有广阔发展前景的剂型。本文综述了近年来受体介导脂质体的研究进展。     

受体介导脂质体的研究进展

配体修饰脂质体通过受体介导的内吞作用主动靶向药物至靶位,增加了药物靶向的特异性,减少了对非靶组织器管损伤,提高了疗效,是一种具有广阔发展前景的剂型。本文综述了近年来受体介导脂质体的研究进展。     

双重修饰的主动靶向脂质体研究进展

主动靶向脂质体是靶向递药体系的一个重要角色。由于传统的单一基团修饰的主动靶向脂质体存在靶向效率不高、细胞摄取率不高等缺点,人们不断探索采用两种或多种不同识别分子或其他协同分子共同修饰脂质体。本文拟针对双重修饰脂质体技术的研究进展进行综述。通过对两种特异性配体或抗体共同修饰、特异性配体与细胞穿透肽共同修饰、两种细胞穿透肽共同修饰等不同类型的双重修饰脂质体的综述分析,我们发现双重修饰技术具有提高靶向准确性和靶向效率,提高药物摄取,提高对靶点的黏附能力和血流稳定性等优势,尤其在跨膜穿越屏障系统的应用中凸显作用。     

抗肿瘤药物靶向载体系统的研究与开发

综述肿瘤靶向给药的基础和抗肿瘤药物靶向载体系统的发展。分类介绍普通被动靶向载药系统（如微乳、传统脂质体、聚合物纳米粒、固体脂质纳米粒、纳米脂质载体、药-脂结合物纳米粒等）、表面修饰的被动靶向载药系统及主动靶向载药系统（如免疫脂质体、免疫聚合物纳米粒及受体-配体介导靶向纳米载体）的研究与开发。在传统药物制剂的基础上，发展抗肿瘤药物的新型靶向载体系统，改善药物在体内的代谢动力学特性，增加药物定向富集到肿瘤部位甚至肿瘤细胞内，提高疗效，降低毒副作用，是近年来备受关注的课题。     

脂质体的药效学研究

脂质体给药系统在降低药物毒性、增加药物在靶点聚集和提高药物疗效等方面起了重要作用。目前已设计出膜上载有或不载靶识别分子的靶向脂质体,包括抗肿瘤药、抗寄生虫药、抗真菌药、激素、多肽、酶类药物及用于疫苗、基因治疗和免疫诊断的药物。本文就脂质体作为药物载体的药效学及应用方面做一综述。     

肝癌靶向的阳离子脂质体共递送多西他赛和siRNA的研究

肝细胞癌是全世界最常见的恶性肿瘤之一,居癌症相关死亡原因第三位。通过存纳米载体系统上修饰靶向配体可将药物主动靶向至肿瘤细胞。随着药物制剂学的发展,采用纳米给药系统共递送化疗药物与基因药物成为了治疗肿瘤的一种手段。本研究通过薄膜超声法制备了共包载多西他赛（DTx）和小干扰RNA（siRNA）的脂质体,并用SP94对其进行修饰。血清稳定性试验表明,脂质体能较好地保护siRNA免受血清中核酸酶的降解。与未修饰的阳离子脂质体相比,SP94修饰的阳离子脂质体显著增强了制剂的在肿瘤细胞内的摄取和对肿瘤细胞的抗增殖作用,表明了SP94的主动靶向作用。本课题成功构建了主动靶向肝癌的共包载DTx和siRNA的阳离子纳米粒给药系统,为肝细胞癌的治疗提供了新的研究思路。     

脂质体修饰性材料应用研究进展

脂质体作为低毒性与免疫原性的药物载体已被应用于难溶性、不稳定、毒性等药物的递送，但传统脂质体仍存在稳定性差、体内循环时间不足、主动靶向性不明显等缺陷，因此选择适宜的修饰性材料制备脂质体已成为必要手段。修饰脂质体的方法主要有：在膜材中加入表面活性剂或改性物质，在膜表面嵌插靶向配体物质，将配体与膜材偶联共同组成脂质体结构。通过总结近年来脂质体常用的修饰性材料，阐释修饰原理并分析其优势及弊端，为脂质体的研究与开发提供借鉴。     

新型脂质体的研究进展

作为药物传递系统的载体,几种新型脂质体如膜融合脂质体、柔性脂质体、表面修饰脂质体等的研究己取得显著进展.本文归纳和分析了近期有关脂质体稳定性、靶向性及修饰材料的文献.     

热敏脂质体

目的:综述热敏脂质体的原理和它作为靶向药物载体的应用。方法:论述了脂质体相变的原理和热敏脂质体的研究概况,以及携带化疗药物的热敏脂质体和肿瘤热疗结合后治疗效果的增强作用,指出了热敏脂质体的发展前景。结果:热敏脂质体有良好的热靶向性,在肿瘤治疗方面效果明显。结论:热敏脂质体是新一代热靶向药物载体,有重要的开发价值。     

Eph A10-modified pH-sensitive liposomes loaded with novel triphenylphosphine–docetaxel conjugate possess hierarchical targetability and sufficient antitumor effect both in vitro and in vivo

Mitochondrial-targeting therapy was considered to be a promising approach for the efficient treatment of cancer while positive charge induced nonspecific cytotoxicity severely limits its application. To overcome this drawback, a novel mitochondria targeted conjugate triphenylphosphine-docetaxel (TD) has been synthesized successfully and incorporated it into liposomes (EPSLP/TD), which possessed excellent pH-sensitive characteristic, EphA 10 mediated active targetability as well as mitochondria-targeting capability. EPSLP/TD was characterized to have a small particle size, high-encapsulation efficiency and excellent pH-sensitive characteristic. Compared with DTX-loaded liposomes (EPSLP/DTX), EPSLP/TD possessed higher cytotoxicity against MCF-7 cell line. Mitochondrial-targeting assay demonstrated mitochondria-targeting moiety triphenylphosphine (TPP) could efficiently deliver DTX to mitochondria. Western immunoblotting assay indicated that EPSLP/TD could efficiently deliver antitumor drug to mitochondria and induce cell apoptosis via mitochondria-mediated apoptosis pathway. In vivo antitumor study demonstrated EPSLP/TD owed excellent in vivo antitumor activity. Histological assay demonstrated EPSLP/TD showed strongly apoptosis inducing effect, anti-proliferation effect and anti-angiogenesis effect. This work investigated the potential of hierarchical targeting pH-sensitive liposomes is a suitable carrier to activate mitochondria-mediated apoptosis pathway for cancer therapy.     

The use and importance of liposomes in Positron Emission Tomography

Among different imaging modalities, Positron Emission Tomography (PET) gained importance in routine hospital practice depending on ability to diagnose diseases in early stages and tracing of therapy by obtaining metabolic information. The combination of PET with Computed Tomography (CT) forms hybrid imaging modality that gives chance to obtain better images having higher resolution by fusing both functional and anatomical images in the same imaging modality at the same time. Therefore, better contrast agents are essentially needed. The advance in research about developing drug delivery systems as specific nanosized targeted systems gained an additional importance for obtaining better diagnosis and therapy of different diseases. Liposomes appear to be more attractive drug delivery systems in delivering either drugs or imaging ligands to target tissue or organ of diseases with higher accumulation by producing in nano-scale, long circulating by stealth effect and specific targeting by modifying with specific ligands or markers. The combination of positron emitting radionuclides with liposomes are commonly in research level nowadays and there is no commercially available liposome formulation for PET imaging. However by conjugating positron emitter radionuclide with liposomes can form promising diagnostic agents for improved diagnosis and following up treatments by increasing image signal/contrast in the target tissue in lower concentrations by specific targeting as the most important advantage of liposomes. More accurate and earlier diagnosis of several diseases can be obtained even in molecular level with the use of stable and effectively radiolabeled molecular target specific nano sized liposomes with longer half-lived positron emitting radionuclides.     

pH值敏感型脂质体表面修饰技术的研究进展

pH 值敏感型脂质体表面修饰已成为脂质体制剂的研究热点,经过表面修饰的pH值敏感型脂质体进入人体后,在此特异性片段的介导下,被靶细胞识别,达到在靶细胞有针对性地释放药物和减少对机体正常组织损害的目的.对pH值敏感型脂质体进行表面修饰的主要目的有3个:延长体循环时间、增强pH值敏感性和提高靶向性.主要从这3方面综述近十年来pH值敏感型脂质体表面修饰的研究进展,为pH值敏感型脂质体表面修饰的进一步研究提供参考.     

RGD肽在肿瘤靶向纳米给药系统中的应用

RGD肽是一类含有精氨酸一甘氨酸一天冬氨酸(Arg-Gly-Asp)的短肽,作为肿瘤细胞或者新生血管特异表达的整合素和其配体相互作用的识别位点,可介导肿瘤的靶向治疗.抗肿瘤药物及其递送系统经过RGD肽修饰.可增加药物的肿瘤主动靶向特性,达到更有效、精确和安全的治疗.本文主要综述了RGD肽在脂质体、聚合物胶束、基因载体等...     

A two-component drug delivery system using Her-2-targeting thermosensitive liposomes

We report on a new method for enhancing the specificity of drug delivery for tumor cells, using thermosensitive immunoliposomes. The liposomes are conjugated to the antibody trastuzumab (Herceptin^®), which targets the human epidermal growth factor receptor 2 (Her-2), a cell membrane receptor overexpressed in many human cancers. Being thermosensitive, the liposomes only release their contents when heated slightly above body temperature, allowing for the possibility of tissue targeting through localized hyperthermia. Using self-quenching calcein, we demonstrate the release of liposome contents into cell endosomes after brief heating to 42°C. To further increase targeting specificity, we incorporate the concept of a two-component delivery system that requires the interaction of two different liposomes within the same endosome for cytoplasmic delivery. Experimental evaluation of the technique using fluorescently labeled liposomes shows that a two-component delivery system, combined with intracellular disruption of liposomes by hyperthermia, significantly increases specificity for Her-2-overexpressing tumor cells.     

包合物脂质体靶向系统在给药中的应用

近年来,包合物和脂质体作为药物的载体被广泛用于药物制剂领域,各自发挥着自身的优势。将环糊精包合物应用于脂质体给药系统——这一新型的药物载体,能够更好地提高靶向给药效果。本文通过概述包合物及脂质体的优势,阐明包合物脂质体这一新型给药系统能提高药物的载药量,增加脂质体的稳定性,对提高药物的吸收和临床疗效等方面具有重要意义,对于靶向给药系统的进一步发展具有新的参考价值。     

Increasing the antitumor efficacy of doxorubicin-loaded liposomes with peptides anchored via a chelator lipid

The therapeutic efficacy of anticancer drugs like doxorubicin can be significantly increased by their incorporation into liposomes, but an ability to actively target the drug-containing liposomes to tumors could well provide an even greater curative effect. In this work, a commercial preparation of doxorubicin-loaded liposomes (Caelyx) was modified by incorporation of the metal chelator lipid 3(nitrilotriacetic acid)-ditetradecylamine (NTA₃-DTDA) to enable engraftment of histidine-tagged targeting molecules. Our results show that when engrafted with p15-RGR, a His-tagged peptide containing a sequence purported to bind platelet-derived growth factor receptor β (PDGFRβ), NTA₃-DTDA-containing Caelyx (3NTA-Caelyx) can be targeted to NIH-3T3 cells in vitro, leading to increased cytotoxicity compared with non-targeted 3NTA-Caelyx. PDGFRβ is known to be expressed on pericytes in the tumor vasculature; however, when radiolabeled p15-RGR liposomes were administered to mice bearing subcutaneous B16-F1 tumors, minimal accumulation into tumors was observed. In contrast, an alternative targeting peptide, p46-RGD, was found to actively direct liposomes to tumors (4.7 %ID/g). Importantly, when injected into tumor-bearing mice, p46-RGD-engrafted 3NTA-Caelyx significantly decreased the tumor growth rate compared with controls. These results indicate that the incorporation of NTA₃-DTDA into liposomal drugs could represent a simple modification to the drug to allow engraftment of targeting molecules and to increase its efficacy.     

Hydroxycamptothecin liposomes based on thermal and magnetic dual-responsive system: preparation,in vitro and in vivo antitumor activity,microdialysis-based tumor pharmacokinetics

Due to the absence of lactone form of hydroxycamptothecin, the commercially available hydroxycamptothecin injection exhibits inefficient therapeutic effects. In this study, we constructed a novel delivery system (thermosensitive magnetic liposomes) that protects lactone form of hydroxycamptothecin from blood or water. After hydroxycamptothecin was loaded into the thermosensitive magnetic liposome (HCPT/TML), its in vitro and in vivo antitumor activity and microdialysis-based tumour pharmacokinetics were determined. The results demonstrated that HCPT/TMLs possessed favourable physicochemical features and significant cytotoxicity against the Huh-7 cells in vitro. In the in vivo antitumor study and tumour pharmacokinetics, HCPT/TMLs displayed effective targeting delivery and antitumor effects, which corresponded to the determined hydroxycamptothecin concentration in tumour tissue. In conclusion, this thermal and magnetic dual-responsive system can efficiently deliver hydroxycamptothecin to tumour tissue and has great potential application in cancer treatment.