磁性药物靶向治疗的进展

磁性药物靶向治疗是利用磁场使具有磁响应的药物聚焦在靶部位，提高靶部位药物的浓度，降低药物对正常组织的毒性和副作用。本介绍和评估了磁性药物靶向治疗的发展，并展望了其未来的前景。     

叶酸磁性纳米颗粒载顺铂抑制人喉癌Hep-2细胞生长且无细胞毒性作用

BACKGROUND: Chemotherapy drugs can kill both cancer cells and normal tissue cells. Molecular targeted therapy can reduce or avoid toxicity of chemotherapy drugs to normal cells. OBJECTIVE: To study the therapeutic effect of folic acid magnetic nanoparticles containing cisplatin on laryngeal cancer. METHODS: Folic acid-cis-diaminodichloroplatinum (II)-aldehyde sodium alginate-magnetic nanoparticles (FA-CDDP-ASA-MNPs) were prepared. The FA-CDDP-ASA-MNPs, CDDP and FA-ASA-MNPs were cultured together with human laryngeal cancer Hep-2 cells. To detect the effect of FA-CDDP-ASA-MNPs, CDDP and FA-ASA-MNPs on human laryngeal cancer Hep-2 cells, MTT, flow cytometry and transmission electron microscopy examination were used in vitro. RESULTS AND CONCLUSION: Both FA-CDDP-ASA-MNPs and CDDP could inhibit the growth of human laryngeal cancer Hep-2 cells, and there was no difference in their inhibitory rates (P > 0.05). FA-CDDP-ASA-MNPs and CDDP showed increased inhibitory rates of human laryngeal cancer Hep-2 cells with the increase of CDPP concentration. The half maximal inhibitory concentrations of CDDP for inhibiting Hep-2 cells were significantly different at 24 and 48 hours after culture (P < 0.05). Both FA-CDDP-ASA-MNPs and CDDP could cause apoptosis in Hep-2 cells, and the number of apoptotic cells was increased with the increase of drug concentrations (P < 0.05), but there was no difference between two kinds of drugs (P > 0.05). FA-CDDP-ASA-MNPs and CDDP at low concentrations could increase the percentage of cells at G0/G1, but decrease the cell proportion at S and G2/M phases (P < 0.05). Under transmission electron microscope, Hep-2 cells with the intake of FA-CDDP-ASA-MNPs appeared to have notable apoptosis. These findings suggest that folic acid magnetic nanoparticles containing cisplatin can inhibit the growth of human laryngeal cancer Hep 2 cells, with no influence on the efficacy of cisplatin and with no cytotoxic effect.       

叶酸靶向载紫杉醇磷脂-聚合物杂化纳米粒的制备及其体外细胞评价

目的 制备具有叶酸靶向性的载紫杉醇磷脂-聚合物杂化纳米粒(PTX-FLPNPs),并研究其对乳腺癌细胞EMT-6的细胞毒性及体外细胞吞噬.方法 以聚己内酯-聚乙二醇-聚己内酯(PCL-PEG-PCL)、二硬脂酰基磷脂酰乙醇胺-甲氧基聚乙二醇(DSPE-mPEG2000)和叶酸偶联的磷脂(Folate-PEG(2000)-DSPE)为药物载体,通过薄膜水化法自组装制备PTX-FLPNPs,并对其进行表征;使用激光扫描共聚焦显微镜观察比较叶酸受体高表达的乳腺癌细胞EMT-6对叶酸靶向及无靶向杂化纳米粒的吞噬作用;采用MTS法研究PTX-FLPNPs对EMT-6细胞的细胞毒性.结果 成功制备了PTX-FLPNPs,其呈球形,粒径均匀,具有明显的“核-壳”结构.投药量为30％的PTX-FLPNPs的平均粒径为(279.9±8.7)nm,多分散系数为0.173±0.021,Zeta电位为(-17.5±1.1)mV,载药量为(27.36±0.91)％,包封率为(91.16±1.12)％.细胞吞噬实验表明,叶酸受体高表达的EMT-6细胞对叶酸靶向的杂化纳米粒的吞噬作用明显强于无靶向的杂化纳米粒(P＜0.05).细胞毒性实验结果表明,PTX-FLPNPs的细胞毒性低于紫杉醇注射剂,且对肿瘤细胞的抑制效果优于无靶向的杂化纳米粒.结论 PTX-FLPNPs具有较高载药量及包封率,粒径均匀,可通过主动靶向作用介导肿瘤细胞内吞,并增加药物在肿瘤细胞内的浓度,是一种能有效抑制肿瘤的靶向载药纳米制剂.     

载顺铂超顺磁γ-Fe2O3纳米粒子的制备与表征*☆

背景：将化疗药物联接在磁性纳米载体上,在外加磁场的引导下使所载药物定向集中于靶向治疗部位,在增强疗效同时还可降低毒性不良反应。 目的：制备海藻酸钠改性的磁性纳米粒子及其负载顺铂药物,分析产物的磁学性质。 方法：通过Fe2+在乙醇胺水溶液中一步合成磁性纳米粒子,用海藻酸钠作偶联剂使磁性纳米粒子与顺铂相连,制备磁性纳米粒子药物。 结果与结论：X射线衍射花样证明产物为γ-Fe2O3纯相,透射电子显微镜表明磁性纳米粒子直径平均约10 nm,载顺铂后药物包覆于纳米粒子周围,磁化曲线显示纳米粒子为超顺磁性,核磁共振得到纳米粒子的弛豫率为0.116 02 mmol/ms。表明所制备磁性纳米粒子及其载顺铂超顺磁性纳米粒子药物性质稳定,具有作为磁性纳米粒子药物的特性。 关键词：磁性纳米粒子药物;顺铂;超顺磁性;Fe2O3;生物材料与药物控释 doi:10.3969/j.issn.1673-8225.2012.12.011     

叶酸偶联白蛋白纳米粒的制备工艺研究

采用去溶剂化法制备普通白蛋白纳米粒 ,利用叶酸活性酯在微碱性条件下与白蛋白纳米粒表面的氨基反应 ,制得叶酸偶联白蛋白纳米粒。采用葡聚糖凝胶柱色谱法及紫外分光光度法验证偶联是否成功 ,并测定叶酸偶联的程度。通过葡聚糖凝胶柱色谱法可以清楚地看到叶酸偶联白蛋白纳米粒与未反应的叶酸活性酯完全分离 ,叶酸偶联白蛋白纳米粒与叶酸白蛋白机械混合物的胰蛋白酶水解液在 35 8nm处的紫外吸收图谱基本一致 ,说明叶酸已经成功地偶联于白蛋白纳米粒的表面。纳米粒形态圆整 ,平均粒径为 6 6 nm。叶酸偶联白蛋白纳米粒制备成功 ,作为叶酸受体表达丰富的多种肿瘤细胞的主动靶向给药的潜在途径 ,值得进一步的关注和研究     

构建叶酸修饰的乳腺癌靶向纳米超声造影微粒

BACKGROUND: Studies have testified that nano-ultrasound contrast agents have a strong permeability, making it possible to image the targeted tissues outside blood vessels and overcome the limitation that micron contrast agents are only available for the blood pool imaging. OBJECTIVE: To construct the folate-modified nanoparticles targeting breast cancer as ultrasound contrast agents, as well as to observe their ability to specifically bind to cells and imaging effect in vitro. METHODS: Both contrast agents, pegylated lactic acid-glycolic acid copolymer wrapping liquid fluorocarbon formed nanoparticles (mPP/PFOB) and folate modified pegylated lactic acid-glycolic acid wrapping liquid fluorocarbon formed nanoparticles (mPPF/PFOB), were constructed by phacoemulsification-evaporation method. (1)Biocompatibility detection: HFF-1 and MCF-7 cells in the logarithmic phase were cultivated with various concentrations (0, 0.005, 0.01, 0.02, 0.05, 0.1, 0.2 and 1 g/L) of mPP/PFOB or mPPF/PFOB for 24 hours respectively, and then the cell viability was measured. (2)Targeting ability detection in vitro: HFF-1 and MCF-7 cells in the logarithmic phase were divided into three groups. Cy5-labled mPP/PFOB and mPPF/PFOB were added into groups A and B, respectively; the cells in group C were pretreated with folate for 2 hours, and sequentially Cy5-labled mPPF/PFOB was added into group C. Fluorescence intensity was detected by flow cytometry after 0.5 hours of culture. The distribution of contrast agents in cells was observed using confocal microscopy after 20 minutes of culture. (3)Ultrasound imaging in vitro: there were three groups: saline was as group A; the suspension of saline and mPPF/PFOB nanoparticles was prepared as group B; MCF-7 cells were resuspended with the mixture of saline and mPPF/PFOB nanoparticles to prepare the suspension of nanoparticles and cells as group C. In each group, the suspension was added into latex gloves, that were then tightened and immersed in water. Finally, the ultrasound was use to detect the ultrasound imaging effect in vitro. RESULTS AND CONCLUSION: Neither nanoparticles were with significant cytotoxicity. The flow cytometry showed that the mean fluorescence intensity in MCF-7 cells of group B was significantly higher than that of groups A and C. But there were no significant differences in the mean fluorescence intensity in HFF-1 cells among the three groups. It was observed that mPPF/PFOB mainly gathered around the MCF-7 cell membrane, while mPP/PFOB randomly distributed in the cytoplasm. After mPPF/PFOB binding to MCF-7 cells, they could enhance ultrasound echo in vitro. These findings indicate that the targeted nanoparticles mPPF/PFOB have good biocompatibility and can specifically bind to breast cancer MCF-7 cells in vitro and enhance the imaging capability.     

肿瘤靶向纳米递药系统的研究进展

该文就纳米粒的发展、纳米技术在肿瘤靶向药物递送中的应用进行综述,并对其存在的问题和发展趋势进行了探讨.     

磁性药物靶向治疗的进展

磁性药物靶向治疗是利用磁场使具有磁响应的药物聚焦在靶部位,提高靶部位药物的浓度,降低药物对正常组织的毒性和副作用。本文介绍和评估了磁性药物靶向治疗的发展,并展望了其未来的前景。     

脑主动靶向载内吗啡肽纳米粒的制备及其镇痛作用的实验研究

目的 制备新型载镇痛药物内吗啡肽的耦联脑主动靶向抗体OX26纳米粒,研究其镇痛作用.方法 利用新型材料超支化聚甘油-聚乳酸-聚乙醇酸(HBPG-PLGA)通过复合乳液法制备载镇痛药内吗啡肽的纳米粒,在其表面耦联转铁蛋白受体单克隆抗体OX26,通过扫描电子显微镜等进行表征;通过尾静脉注射不同配方纳米粒,考察纳米粒透过血-脑屏障及其对慢性坐骨神经结扎(CCI)大鼠模型镇痛作用.结果 载内吗啡肽HBPG-PLGA纳米粒制备方法稳定,在扫描电子显微镜下呈核壳结构,平均粒径(170±20)nm,Zeta电位约-27 mV,与抗体OX26的耦联效果较好,药物可以缓慢释放72 h以上.尾静脉注射耦联抗体OX26载内吗啡肽纳米粒对CCI大鼠具有较好的镇痛作用,未耦联抗体OX26纳米粒只在给药后45 min时间点显示微弱镇痛作用,静脉注射内吗啡肽和空白纳米粒未显示镇痛作用.结论 耦联抗体OX26载内吗啡肽纳米粒制备稳定,达到较好透血-脑屏障作用,对CCI大鼠有良好镇痛作用.     

药物靶向、分子靶向、激素靶向及干细胞靶向与骨质疏松症的治疗

背景：骨质疏松症引起的骨折及其他并发症严重影响中老年人生活质量。 目的：探讨靶向疗法治疗骨质疏松的进展,以促进其临床应用。 方法：由第一作者应用计算机检索PubMed、中国期刊全文数据库(CNKI)中1997-05/2011-12相关文献。在标题、摘要、关键词中以“targeted therapy,bone target,stem cell,osteoporosis,treatment”或“靶向治疗,骨靶向,干细胞,骨质疏松,治疗”为检索词进行检索。选择文章内容与靶向疗法治疗骨质疏松有关者,同一领域则选择近期发表在权威杂志上的文章。 结果与结论：初检得到148篇文献,根据纳入标准选择38篇文献进行综述。靶向治疗骨质疏松已成为骨质疏松治疗中的研究热点。目前研究领域涉及药物靶向、分子靶向、激素靶向、受体靶向及干细胞靶向治疗等,其中药物、分子及激素靶向疗法为目前常用的治疗方法,常用药物有四环素、双膦酸盐类、Denosumab等。但目前靶向治疗骨质疏松尚未完全成熟,所导致的临床不良反应限制其应用进展,仍有许多问题有待解决。     

布洛芬磁性固体脂质纳米粒的制备

背景：布洛芬因溶解度和溶血问题,目前仍无注射给药剂型上市。 目的：将自制的磁流体载入固体脂质纳米粒中,制备布洛芬磁性固体脂质纳米粒。 方法：以包封率为指标,用正交设计确定布洛芬固体脂质纳米粒的最优处方。以共沉淀法制备Fe3O4磁流体作为磁性材料,采用乳化分散-超声法,按照最优处方制备布洛芬磁性固体脂质纳米粒。观察其表面形态、粒径大小、分布和Zeta电位、饱和磁化强度、包封率及体外释放特征。 结果与结论：通过正交实验得最优处方为布洛芬0.05 g、F-68 0.2 g、吐温80 0.05 g、卵磷脂0.1 g、单硬脂酸甘油酯0.05 g、磁流体2.5 mL。用该工艺和处方制备的布洛芬磁性固体脂质纳米粒粒子呈均匀球形;平均粒径、zeta电位为(122±16) nm和(-13.3±6.94) mV;药物包封率和Fe3O4铁包封率分别为84.15%和83.19%;布洛芬在给定介质中36 h释放较完全,符合制剂学性质要求。     

Synthesis, characterization and in vitro drug release of magnetic N-benzyl-O-carboxymethylchitosan nanoparticles loaded with indomethacin

Magnetic N-benzyl-O-carboxymethylchitosan nanoparticles were synthesized through incorporation and in situ methods and characterized by Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and magnetization measurements. Indomethacin was incorporated into the nanoparticles via the solvent evaporation method. The indomethacin-loaded magnetic nanoparticles were characterized by the same techniques, and also by transmission electron microscopy. The nanoparticles containing the polymer showed a drug loading efficiency of between 60.8% and 74.8%, and the magnetic properties were not significantly affected by incorporation of the drug. The in vitro drug release study was carried out in simulated body fluid, pH 7.4 at 37°C. The profiles showed an initial fast release, which became slower as time progressed. The percentage of drug released after 5 h was between 60% and 90%, and the best fitting mathematical model for drug release was the Korsmeyer-Peppas model, indicating a Fickian diffusion mechanism.     

Preparation and characterization of magnetic thermosensitive fluorouracil micelles

In this study, we synthesized P(NIPAM-co-DMAM)-b-PLA polymers with free radical polymerization and ring-opening addition polymerization, and immediately assembled ‘dextran magnetic layered double hydroxide fluorouracil’ (DMF) magnetic particles into the core of the amphiphilic polymer micelles with synchronous hydration and dialysis, to generate a magnetic thermosensitive fluorouracil drug delivery system. The basic properties of the micelle particles, such as the core–shell-type structure, size, and zeta potential, were studied with ¹H-NMR, FTIR, TEM, TGA, laser nanoparticle size analysis, and other characterization techniques. The thermosensitivity of the micelles was investigated by measuring parameters such as the lower critical solution temperature (LCST) and the relationship between the particle size variation and temperature. The drug release curves for the micelles at different temperatures were constructed with a dialysis method. The LCST of the triblock polymers was 42 °C. The particle sizes of the blank micelles and DMF-loaded micelles were 493.6 ± 1.8 nm and 464.9 ± 4.1 nm, respectively, at 25 °C. When the temperature was higher than LSCT, a contraction phase change in the micelle structure occurred, a significant characteristic of the core–shell-type structure, and reversible phase transition phenomena. The release behavior of the drug-loaded micelles showed obvious variations with temperature. Therefore, the magnetic thermosensitive fluorouracil drug delivery system has a good magnetic response and excellent temperature controlled release characteristics, so it can be used as a drug delivery system in magnetically and thermally targeted chemotherapy for tumors.     

Preparation and characterization of interferon-loaded magnetic biodegradable microspheres

In this work, magnetite (Fe(3)O(4)) nanoparticles with an average size 10 nm modified by sodium oleate were prepared by the modified controlled chemical coprecipitation method, which can be well dispersed in water and linked well with protein molecules because of the presence of -COOH on their surface. Then magnetic poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) microspheres containing interferon alpha-2b (IFN-a-2b) were prepared by the modified water-in-oil-in-water solvent evaporation procedure. X-ray powder diffraction analysis, particle size analysis, transmission electron microscopy, scanning electron microscopy, and vibrating-sample magnetometer (VSM) analysis were carried out to examine phase composition, surface and interior morphology, size and size distribution, and magnetic properties of the magnetic microspheres. Also the effects of some important parameters on the magnetic biodegradable microspheres were investigated, such as magnetite dosage in the preparation system, stirring rate of the suspension medium, and concentration of the external aqueous phase. And the antiviral activity of IFN-a-2b encapsulated in the magnetic polymeric microspheres was evaluated by the vesicular stomatitis virus (VSV) cytopathicity inhibition assay. The results showed that the properties of IFN-loaded magnetic PLGA and PLA microspheres were better than the conventional protein-loaded polymeric microspheres, such as perfect magnetic properties, higher protein encapsulation efficiency, and less effect on the antiviral activity of protein. These indicated that the magnetic PLA and PLGA microspheres containing IFN-a-2b exhibited strong potential as targeted-drug delivery vehicles, which could be rapidly localized to the immunization-related tissues easily by an external magnetic field.     

The preparation and characterization of folate-conjugated human serum albumin magnetic cisplatin nanoparticles

Objective

Nanoparticles are becoming an important method of targeted drug delivery. To evaluate the importance of folate-conjugated human serum albumin (HSA) magnetic nanoparticles (Folate-CDDP/HSA MNP), we prepared drug-loaded Folate-CDDP/HSA MNPs and characterized their features.

Methods

First, folate was conjugated with HSA under the effect of a condensing agent, and the conjugating rate was evaluated by a colorimetric method using 2, 4, 6 - trinitrobenzene sulfonic acid. Second, under N₂ gas, Fe₃O₄ magnetic nanomaterials were prepared and characterized by using transmission electron microscopy (TEM), SEM-EDS and X-ray diffraction (XRD). Finally, Folate-CDDP/HSA MNP was prepared by using a solvent evaporation technique. TEM was used to observe particle morphology. The particle size and distribution of the prepared complexes were determined by a Laser particle size analyzer. Drug loading volume and drug release were investigated by a high performance liquid chromatography method (HPLC) in vitro.

Results

We successfully prepared folate-conjugated HSA and its conjugating rate was 27.26 µg/mg. Under TEM, Fe₃O₄ magnetic nanoparticles were highly electron density and had an even size distribution in the range of 10-20 nm. It was confirmed by SEM-EDS and XRD that Fe₃O₄ magnetic nanoparticles had been successfully prepared. Under TEM, drug-loaded magnetic nanoparticles were observed, which had a round shape, similar uniform size and smooth surface. Their average size was 79 nm which was determined by laser scattering, and they exhibited magnetic responsiveness. Encapsulation efficiency was 89.75% and effective drug loading was calculated to be 15.25%. The release results in vitro showed that the half release time (t½) of cisplatin in cisplatin Solution and Folate-CDDP/HSA MNP was 65 min and 24 h respectively, which indicated that microspheres had an obvious effect of sustained-release.

Conclusion

Folate-CDDP/HSA MNPs were prepared successfully. The preparation process and related characteristics data provided a foundation for further study, including the mechanism of the nanoparticles distribution in vivo and their intake by tumor cells.     

Dual docetaxel/superparamagnetic iron oxide loaded nanoparticles for both targeting magnetic resonance imaging and cancer therapy

Theragnostics polymer nanoparticles (NPs) loaded simultaneously with anticancer drug docetaxel (Dtxl) and superparamagnetic iron oxide (SPIO) nanocrystals were developed for both cancer therapy and ultrasensitive MRI. These multifunctional polymer vesicles were formed by carboxy-terminated poly(lactic-co-glycolic) acid using a single emulsion evaporation method. The active tumor-targeting single chain prostate stem cell antigen antibodies (scAb(PSCA)) were conjugated on the surface of polymer vesicles by using functional poly(ethylene glycol). The diameter of NPs was about 147 nm and the SPIO and drug encapsulation efficacy was 23% and 6.02%, respectively. Vibration simple magnetometer and X-ray diffraction proved that the superparamagnetic behavior of SPIO was not changed during NPs formation and modification. The NPs exhibited a triphasic drug release pattern in vitro over 30 days. Enhanced cellular uptake ability and antiproliferative effect of the targeted NPs in prostate cancer PC3 cell line by using the confocal laser scanning microscopy and cytotoxicity assay were observed. Moreover, the Prussian blue staining and the MRI assay in vitro demonstrated that the NPs have a high SPIO clustering effect. Therefore, these stable and tumor-targeting polymer NPs could be promising multifunctional vesicles for simultaneous targeting imaging, drug delivery and real time monitoring of therapeutic effect.     

Fe3O4磁性微粒的制备及表征

背景：磁性微粒作为一种磁性载体在固定化酶、免疫检测、靶向载药治疗及细胞分离等生物医学领域得到了广泛的应用。 目的：制备分散稳定性好,相对磁性强的纳米级Fe₃O₄微粒。 方法：以氯化亚铁、氯化铁、氢氧化钠为主要原料,采用化学共沉淀法合成Fe₃O₄磁性粒子。 结果与结论：用正交设计法优化了Fe₃O₄微粒的合成工艺条件,得到制备Fe₃O₄粒子的最佳实验条件为Fe²⁺/Fe³⁺的物质的量之比为2∶1、共沉淀时的pH值为11、熟化温度为90 ℃、表面活性剂聚乙二醇的用量为40 mL,此时制得的Fe₃O₄粒子粒径最小,为78 nm,Fe₃O₄溶液的分散稳定性最好,相对磁性最强。从Fe₃O₄的扫描电镜图可以看出,Fe₃O₄微粒晶体颗粒为纳米级。     

Preparation and Characterization of HLA-A＊0201 Tetramer Loaded with IE-1316.324 Antigenic Peptide of Human Cytomegalovirus

Major histocompatibility complex （MHC） class I tetramer technology has become the central technique for analyzing antigen-specific CD8^＋ T cell responses and it has been widely used to explore the differentiation and formation of memory CD8^＋ T cells. Previously, a simplified and efficient procedure for preparing high quality HLA-A＊0201 tetramers has been established in our lab and the tetramers loaded with HCMV peptide pp6549s.50a has been successfully applied to investigate HCMV-specific CD8^＋ T cells in Chinese populations. Using similar procedure we reported here the construction of HLA-A＊0201 tetramer loaded with another dominant epitope derived from immediate early （IE）-1 316.324 （VLEETSVML, VLE） of HCMV （A2-VLE） and characterization of this tetramer. After A2-VLE monomer was prepared and purified, its tetramer was then formed at a yield of 83%. The optimized amount of A2-VLE tetramer for staining 100 μl whole blood was 0.5 μg with incubation at 4℃ for 1 h. Furthermore, the dissociation constant of the tetramer binding to the specific CD8^＋ T cells of one HLA-A2^＋ donor was estimated to be 32.7 nmol/L, which is markedly higher than that of MHC monomer. The construction of A2-VLE tetramer provides an alternative choice for investigating HCMV-specific CD8^＋ T cell responses and will deepen our understanding of the differentiation and formation of HCMV-specific memory CD8^＋ T cells. Cellular ＆ Molecular Immunology.     

磁性聚乳酸-羟基乙酸氧化苦参碱纳米粒的制备及其特性

目的研究磁性聚乳酸-羟基乙酸氧化苦参碱纳米粒(M-PLGA-OM-NP)的制备工艺,并对纳米粒子进行评价。方法运用复乳法制备M-PLGA-OM-NP,通过透射电子显微镜观察纳米粒形态,并对纳米粒的平均粒径、载药量、包封率、体外释药情况等进行评价。结果纳米粒外观呈规则球形,其平均粒径为146.5 nm,载药量为7.61%,包封率为44.8%。突释后至第72小时,纳米粒维持较稳定的释药速度,累积释放达52.9%。72～240 h,药物释放缓慢,累计释放约为16.6%,体外释放符合Ritger peppas方程lny=1.280 6+lnt。氧化苦参碱药性不受温度影响。结论获得了较满意的M-PLGA-OM-NP制备工艺,其过程简单,粒子性状符合要求。     

Paclitaxel loaded liposomes decorated with a multifunctional tandem peptide for glioma targeting

The treatment of glioma is a great challenge because of the existence of the blood-brain barrier (BBB). In order to reduce toxicity to the normal brain tissue and achieve efficient treatment, it is also important for drugs to specifically accumulate in the glioma foci and penetrate into the tumor core after entering into the brain. In this study, a specific ligand cyclic RGD peptide was conjugated to a cell penetrating peptide R8 to develop a multifunctional peptide R8-RGD. R8-RGD increased the cellular uptake of liposomes by 2-fold and nearly 30-fold compared to separate R8 and RGD respectively, and displayed effective penetration of three-dimensional glioma spheroids and BBB model in vitro. In vivo studies showed that R8-RGD-lipo could be efficiently delivered into the brain and selectively accumulated in the glioma foci after systemic administration in C6 glioma bearing mice. When paclitaxel (PTX) was loaded in liposomes, R8-RGD-lipo could induce the strongest inhibition and apoptosis against C6 cells and finally achieved the longest survival in intracranial C6 glioma bearing mice. In conclusion, all the results indicated that the tandem peptide R8-RGD was a promising ligand possessing multi functions including BBB transporting, glioma targeting and tumor penetrating. And R8-RGD-lipo was proved to be a potential anti-glioma drug delivery system.