转铁蛋白修饰磁性纳米粒的制备及其体外抗肿瘤活性研究

目的:本研究旨在构建一种转铁蛋白修饰负载阿霉素(DOX)的磁纳米粒靶向递药系统,以提高阿霉素作用的靶向性。方法:采用化学共沉淀法制备转铁蛋白修饰负载阿霉素的磁性纳米粒(DOX@MNP),采用zeta电位及纳米粒度分析仪测定DOX@MNP的粒径及其zeta电位,透析法评价DOX@MNP的体外释药特征。通过MTT实验,研究DOX@MNP与游离DOX对A549细胞的细胞毒性,通过激光共聚焦显微镜和流式细胞仪观察A549细胞对DOX@MNP与游离DOX的摄取情况。结果:DOX@MNP的释药具有p H依赖性。MTT实验结果显示,DOX@MNP与游离DOX具有相当的细胞毒性;激光共聚焦显微镜和流式细胞仪检测结果显示A549细胞对DOX和DOX@MNP的摄取没有明显差异。结论:本文构建了一种转铁蛋白修饰包载阿霉素的磁纳米粒,体外结果显示其具有与游离DOX相当的细胞毒性,为进一步进行体内实验奠定了基础。     

胆甾醇基γ-聚谷氨酸负载阿霉素纳米胶束的制备与体内外释药性能评价

笔者制备了胆甾醇基γ-聚谷氨酸负载阿霉素纳米胶束(DOX/NPs),并考察了该载药纳米胶束体系的形态与粒径、载药量、包封率以及体内外释药的特性。结果表明:DOX/NPs的最佳载药量为22.4%,包封率为90.2%,平均粒径为(312.3±7.2)nm,电镜下观察呈现明显的核壳结构。体外释药结果显示,DOX/NPs能延缓阿霉素的释放,并具有p H敏感的释药特性。小鼠体内释药结果表明:阿霉素经包埋后其消除半衰期(t1/2)、药时曲线下面积(AUC)、平均滞留时间(MRT)均明显大于游离阿霉素,达到了药物缓释的目的。     

酸敏阿霉素脂质纳米粒的制备及其体外抗肿瘤活性研究

目的:本研究旨在制备具有被动靶向和酸敏特性的脂质混合纳米粒,以期提高阿霉素(doxorubicin,DOX)的靶向递药效率,降低DOX的毒副作用,提高抗肿瘤活性。方法:采用微乳法制备磷酸钙纳米粒核,薄膜分散法制备脂质混合纳米粒,硫酸铵梯度法包封DOX。采用透射电镜观察外观形态,用zeta电位及纳米粒度分析仪测定纳米粒的粒径及zeta电位,透析法评价阿霉素脂质纳米粒体外释药特征。用MTT方法研究阿霉素脂质混合纳米粒对A549细胞的细胞毒性。采用流式细胞仪和激光共聚焦显微镜观察A549细胞对阿霉素脂质纳米粒的摄取。结果:体外释药结果显示阿霉素脂质纳米粒具有酸敏特性。流式结果说明A549细胞对阿霉素脂质纳米粒的摄取具有明显的时间依赖性,激光共聚焦显示阿霉素脂质纳米粒能将阿霉素递送至细胞核中。结论:阿霉素脂质体对A549细胞有明显的细胞毒性,为进一步进行体内实验提供了基础。     

双重响应二硫化钼纳米载药体系的制备及其性能研究

摘要 目的：制备肿瘤微环境响应释放的靶向二硫化钼纳米载药体系,并评价其载药量和释药性能。方法：以水热法合成的MoS₂纳米片为基底,利用MoS₂纳米片上的S空缺位点连接硫辛酸聚乙二醇羧酸,然后通过酰胺反应连接精氨酸-甘氨酸-天冬氨酸（RGD）靶向分子,再连接上交联剂3-(2-吡啶二硫代)丙酸N-琥珀酰亚胺酯（SPDP）,得到药物载体MoS2-PEG-RGD-SPDP（MPRS）,MPRS进一步与巯基化的阿霉素（DOX）反应,形成MPRS-DOX纳米载药体系。通过透射电子显微镜（TEM）,X-射线光电子能谱仪（XPS）以及纳米粒度电位仪对合成的材料进行表征;利用紫外可见分光光度计测试MPRS的载药性能,采用荧光分光光度计考察MPRS-DOX的释药性能。结果：成功合成MPRS-DOX纳米载药体系,其粒径大小在200 nm左右,Zeta电位为+28.2 mV;其载药效率为86.8%,载药量为53.5%。体外释药实验表明,在10 mM 谷胱甘肽（GSH）和pH=5.5的条件下DOX释放量最多。结论：成功制备了粒径合适的MPRS-DOX纳米载药体系,MPRS-DOX具有GSH和pH双重响应性,可实现预期的模拟肿瘤微环境内控制释放药物。这种GSH和pH双重响应的纳米载药体系为新一代刺激响应型纳米载药系统的构建提供了新的思路。     

共载依克立达和阿霉素的PBM-Hz-PEG纳米粒制备与性能研究

摘要 目的：研究不同比例依克立达（ELC）和阿霉素（DOX）的联合抗肿瘤效果,确定最佳联用比例。以生物可降解材料聚苹果酸苄基酯（PBM）为载体包封两种药物,得到一种酸敏感纳米胶束。方法：以L-天冬氨酸为原料通过内酯开环法制备PBM,并以酸敏感的腙键（Hz）连接PEG,得到嵌段聚合物PBM-Hz-PEG,红外光谱和核磁氢谱对其结构进行表征。动态透析法制备纳米胶束,测定纳米胶束的粒度、分散系数（PDI）、临界胶束浓度（CMC）及其载药量（DL）、包封率（EE）。动态透析法模拟胶束的体外释药性能,采用三阴性乳腺癌MDA-MB-231细胞系考察载药纳米胶束的体外细胞毒性。结果：①ELC能够增敏DOX,二者摩尔比为1:3时有最强肿瘤抑制作用。②经红外光谱和核磁共振氢谱表征,嵌段共聚物PBM-Hz-PEG成功合成。③空白纳米胶束的粒径为69.67±11.55 nm,PDI为0.245 ± 0.026,CMC值为3.9 μg?mL^-1;载药纳米胶束粒径略大,粒径在96.92 ~ 113.47 nm之间,ELC和DOX的载药量与投料比一致。④载药纳米胶束在pH 7.4和pH 6.0时的药物释放率曲线和体外细胞毒性试验证实载药胶束具有良好的酸敏特性。结论：ELC和DOX联用有较强的肿瘤抑制作用,PBM是二者的优良载体。该PBM-Hz-PEG纳米胶束载药率高,其特有的酸敏性能够有效降低药物对正常组织的毒副作用,具有肿瘤组织富集释放特性,有望成为一种新型智能释药平台。     

巨噬细胞装载纳米颗粒用于药物递送

目的:活细胞药物递送系统具有主动靶向至肿瘤部位,防止被免疫系统清除等诸多优势。本文提供了一种巨噬细胞负载纳米颗粒的递送方法,并探讨不同载药量对巨噬细胞的活性以及运动性的影响。方法:通过超声乳化法制备包载阿霉素的DOX@PLGA纳米颗粒。纳米粒度分析仪测量粒径和表面电位,透射电镜观察纳米颗粒形态。将DOX@PLGA纳米颗粒与巨噬细胞共同孵育,即得到负载DOX@PLGA纳米颗粒的巨噬细胞用以药物递送。然后通过CCK-8法、LDH法以及细胞迁移实验检测不同载药量情况下细胞活力水平、细胞损伤程度以及细胞运动性。结果:制备的DOX@PLGA纳米颗粒呈圆形或椭圆形,粒径为109.2±2.3 nm;表面电位为-45.0±2.0 m V;载药量为4.61%。当单个巨噬细胞负载0.15 pg DOX时细胞存活率为:71.5±4.4(%);细胞损伤率为:26.3±1.8(%);迁移率为:61.6±5.7(%)。结论:成功制备巨噬细胞负载DOX@PLGA纳米颗粒的递药系统,载药量适当的情况下载体细胞依然具有良好的活性和运动性。     

线粒体靶向TPP-DOX连接物的制备及其逆转肿瘤耐药活性研究

目的:阿霉素(DOX)是常用的抗肿瘤药物,但是它的毒副作用大,而且肿瘤细胞易对DOX产生耐药,限制了其临床应用。本研究利用肿瘤细胞线粒体跨膜电位较高的特性,将亲脂性阳离子(3-丙羧基)三苯基溴化膦(TPP)与DOX相连接制备具有线粒体靶向功能的TPP-DOX,以期达到逆转肿瘤细胞耐药的目的。方法:以DOX、TPP为原料,合成TPP-DOX,通过核磁、质谱等方法进行结构鉴定。采用MTT方法研究TPP-DOX对KB细胞、A549细胞及耐DOX肿瘤细胞MDA-MB-231/ADR的体外抗肿瘤活性。采用激光共聚焦显微镜观察TPP-DOX在肿瘤细胞内的分布。结果:TPP-DOX对KB细胞和A549细胞的毒性低于DOX,TPP-DOX对耐DOX肿瘤细胞MDA-MB-231/ADR的毒性明显大于DOX。激光共聚焦显示TPP-DOX分布于细胞核和线粒体中。结论:TPP-DOX具有线粒体靶向特性,可有效逆转肿瘤耐药,有进一步研究的价值。     

pH和近红外光双响应的包裹二硫化钼纳米片和阿霉素的金属-有机框架ZIF-8用于肿瘤化学/光热协同治疗

利用金属-有机框架材料ZIF-8包裹二硫化钼(MoS_2)纳米片和阿霉素(DOX)构建一种可通过酸性pH和近红外(NIR)光双触发的肿瘤化学/光热协同治疗体系。首先,通过水热反应和超声处理制备粒径为～100 nm、厚度为0.3～1.4 nm的MoS_2纳米片。然后,通过一步法将可酸降解的金属-有机框架ZIF-8包裹在所制备的MoS_2纳米片上,并同时装载抗肿瘤药物DOX,形成装载DOX的ZIF-8包裹MoS_2纳米复合物(DOX/MoS_2@ZIF-8)。将该纳米复合物应用到肿瘤细胞的化学/光热协同治疗:当处于酸性条件(例如:溶酶体中pH大约为5)和NIR激光(780 nm,2.1 W/cm~2)照射的情况下,DOX/MoS_2@ZIF-8纳米复合物上包裹的ZIF-8金属-有机框架会发生酸降解,释放出所包裹的DOX,细胞质中的DOX可以进入细胞核中诱导细胞凋亡;同时,MoS_2纳米片能够将光能转换为热能,光致高温同样能诱导细胞凋亡,因此,化学/光热协同肿瘤治疗得以实现。细胞存活率试验证明:该DOX/MoS_2@ZIF-8纳米复合物在SMMC-7721细胞上表现出良好的化学/光热协同治疗作用,能够对肿瘤细胞进行高效地杀伤。     

阿霉素-姜黄素聚氰基丙烯酸正丁酯复方纳米粒的研制及逆转MCF-7/ADR细胞多药耐药的研究

采用乳化聚合法制备阿霉素-姜黄素聚氰基丙烯酸正丁酯复方纳米粒(DOX-CUR-PBCA-NPs),该纳米粒平均粒径为133±5.34nm,Zeta电位为+32.23±4.56 mV,阿霉素(DOX)和姜黄素(CUR)的包封率分别为49.98±3.32％,94.52±3.14％.MTT实验结果和Western blott实验结果均表明,DOX-CUR-PBCA-NPs与CUR-PBCA-NPs+DOX-PBCA-NPs体外对MCF-7/ADR细胞的生长抑制活性相当,下调MCF-7/ADR细胞中P-糖蛋白(P-gp)的表达也相当,较没有用PBCA纳米粒包载的游离药物、单一药物的纳米制剂及其他形式的制剂联用的抗肿瘤活性及逆转多药耐药的性能都显著增强.说明利用PBCA纳米粒同时包裹抗癌药物阿霉素与中药逆转剂姜黄素协同用药可以增强克服多药耐药(MDR)的疗效.     

PF127修饰的石墨烯复合材料的制备及其载药系统研究

实验制备负载阿霉素的PF127修饰的还原态石墨烯复合材料,并对其性能进行研究和评价。其方法是首先制备由弗朗尼克F127非共价功能化修饰的还原氧化石墨烯材料,记为PF127/GN,然后将该复合物对药物阿霉素进行负载,记为PF127/GN/DOX,并与未经阿霉素负载的纳米药物载体（PF127/GN）进行对比分析。观察其药物释放行为,细胞内递送过程和细胞毒性。研究发现,PF127/GN粒子大小为80μm左右,且粒子分布较均匀,厚度约增加至9.646μm;利用阿霉素对纳米载体进行负载之后,负载效果随药物浓度的增加而不断提高,负载在氧化石墨烯表面的阿霉素的释放行为可通过改变体系的pH值进行调节。负载了阿霉素的纳米药物载体能够发挥良好的释放作用,具有相对较强的生物毒性。因此经过阿霉素负载的PF127修饰的还原态石墨烯复合材料性能良好,具有广阔的应用前景。     

Co-delivery of Vorinostat and Etoposide <Emphasis Type="Italic">Via</Emphasis> Disulfide Cross-Linked Biodegradable Polymeric Nanogels: Synthesis,Characterization, Biodegradation,and Anticancer Activity

Treatment regimens for cancer patients using single chemotherapeutic agents often lead to undesirable toxicity, drug resistance, reduced uptake etc. Combination of two or more drugs is therefore becoming an imperative strategy to overcome these limitations. A step forward can be taken through delivery of the drugs used in combination via nanoparticles. Co-administration of chemotherapeutic drugs encapsulated in nanoparticles has been shown to result in synergistic effects and enhanced therapeutic efficacy. In present study, we explored the combination treatment of histone deacetylase inhibitor vorinostat (VOR) and topoisomerase II inhibitor etoposide (ETOP). The concurrent combination treatment of VOR and ETOP resulted in synergistic effect on human cervical HeLa cancer cells. VOR and ETOP were encapsulated into poly(ethylene glycol) monomethacrylate (POEOMA)-based disulfide cross-linked nanogels. The nanogels were synthesized using atom transfer radical polymerization (ATRP) via cyclohexane/water inverse mini-emulsion and were degradable in presence of intracellular glutathione (GSH) concentration. Both the drugs were loaded into the nanogels by physical encapsulation method and characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X-ray diffraction (XRD), dynamic light scattering (DLS), and differential scanning calorimetry (DSC). Both VOR- and ETOP-loaded nanogels showed sustained release profile. Furthermore, combination treatment drugs encapsulated of POEOMA nanogel demonstrated enhanced synergistic cytotoxic effect compared with combination of free drugs. Enhanced synergistic cell killing efficiency of drug-loaded POEOMA nanogels was due to increased apoptosis via caspase 3/7 activation. Therefore, combination of VOR- and ETOP-loaded PEG-based biodegradable nanogels may provide a promising therapy with enhanced anticancer effect.     

Characterization and in vitro cytotoxicity of doxorubicin-loaded γ-polyglutamic acid-chitosan composite nanoparticles

In this study, γ-polyglutamic acid (γ-PGA) and chitosan (CS) nanoparticles were characterized as a carrier for the anti-cancer drug doxorubicin (DOX). Using ionic complexation between the positively charged DOX and the negatively charged polyelectrolyte γ-PGA, DOX:γ-PGA complexes were produced with an efficiency of approximately 99%. SEM micrographs demonstrated that the complexation of γ-PGA and DOX alone does not lead to the formation of nanoparticles and that the addition of a third component, chitosan, is required. Drug-loaded DOX:γ-PGA:CS nanoparticles were produced with particle sizes ranging from ~150 to ~630 nm. The stability of the DOX:γ-PGA:CS nanoparticles was examined by suspending the nanoparticles in different kinds of aqueous media. For the first time, in vitro studies with DOX-loaded nanoparticles demonstrated the cytotoxicity of the nanoparticles against a human oral squamous cell carcinoma cell line (HN-5a). Non-drug-loaded γ-PGA:CS nanoparticles did not display cytotoxic effects. It was shown that the encapsulated or surface-bound DOX did not lose its bioactivity and the prepared drug-loaded particles exhibited a considerable anti-proliferative activity against the human cancer cell line.     

Thermo-sensitivity and triggered drug release of polysaccharide nanogels derived from pullulan-g-poly(l-lactide) copolymers

Thermo-responsive nanogels from poly(l-lactide)-g-pullulan (PLP1 and 2) copolymers with different lactide contents were investigated as an anticancer drug delivery carrier. The phase transition temperature of PLP 1 with lower lactide content in distilled water showed around 35 °C. Upon adding 0.15 M NaCl to PLP 1, a significant difference in the transmittance was observed when comparing the non-additive salt condition. The total amount of released doxorubicin (DOX) from the DOX-loaded PLP nanogels increased with increasing temperature for 50 h. A noticeable difference in the initial release by PLP 1 was observed between 37 and 42 °C. In the 50% inhibitory concentration (IC₅₀) analysis, the IC₅₀ values of DOX released from PLP 1 were approximately 5.9 and 9.3 μg/mL at 37 and 42 °C, respectively. The results suggest that self-assembled PLP nanogels, by means of a triggering temperature, can be used as a long-term drug delivery system in cancer treatments.     

Hollow chitosan/poly(acrylic acid) nanospheres as drug carriers

The preparation, in-vitro release, in-vitro cytotoxicity, and in-vivo drug delivery of doxorubicin (DOX)-loaded chitosan (CS)-poly(acrylic acid) (PAA) hollow nanospheres were investigated. The loading was done by dissolving a certain amount of DOX in non-cross-linked CS-PAA nanospheres aqueous solution followed by cross-linking chitosan with glutaraldehyde. The drug-loading content was up to 4.3% and the size of drug-loaded hollow nanospheres, determined by dynamic light scattering, was 118 nm. The nanospheres showed a continuous release of the entrapped DOX up to 10 days in vitro and showed comparable in-vitro cytotoxicity against HepG2 cells compared to the free DOX. In-vivo DOX delivery of DOX-loaded CS-PAA nanospheres showed that DOX concentration in blood can be maintained for a longer period than free DOX solution, and the DOX concentration in mice liver can be maintained constantly at relatively high level. The interesting feature of DOX-loaded CS-PAA hollow nanopspheres is that the loaded DOX can be delivered into the mice brain. The confocal laser scanning microscopy analysis reveals that fluorescein isothiocyanate (FITC)-labeled CS-PAA can deposit in different organs including liver, spleen, and brain.     

D-甘露糖修饰聚合物胶束的制备及其在靶向药物输送中的应用

聚合物胶束作为药物载体具有良好的稳定性和生物相容性,提高疏水性药物溶解性等优势,是一类很有应用潜力的药物传输系统。本研究以合成的共价键连D-甘露糖的双亲性聚合物分子(PGMA-Mannose)为药物载体,包载抗癌药物阿霉素(DOX)制备具有甘露糖受体靶向性和pH敏感药物释放特性的新型载药聚合物胶束。利用激光共聚焦显微镜和MTT细胞毒性评价方法对载药胶束的细胞内吞摄取和毒性进行评价。实验结果表明,载药胶束能特异性识别人乳腺癌细胞MDA-MB-231表面过度表达的甘露糖受体,被癌细胞大量摄取并在细胞溶酶体酸性环境内释放药物,而载药胶束在表面甘露糖受体低表达的HEK293细胞中只有少量摄取。与原药DOX相比,该载药胶束对癌细胞的毒性显著提高,而对正常细胞的毒性较低。因此,该PGMA-Mannose聚合物胶束有望成为一种新型的靶向药物输送系统应用于癌症的治疗。     

In vitro release behavior and cytotoxicity of doxorubicin-loaded gold nanoparticles in cancerous cells

Doxorubicin (DOX), a common cancer chemotherapeutics, was conjugated to folate-modified thiolated-polyethylene glycol-functionalized gold nanoparticles. The in vitro, controlled release behavior of DOX-loaded gold nanoparticles was observed using porous dialysis membranes (cut-off = 2 kDa). DOX-loaded gold nanoparticles had higher cytotoxicity for folate-receptor-positive cells (KB cells) compared to folate-receptor-negative cells (A549 cells) which were 48 and 62% viable for 10 μM doxorubicin, respectively. This indicates the potential of these nano-carriers for targeted-delivery. In addition, healthy cell viability was 69% for 10 μM free doxorubicin whereas for the same content of drug in DOX-loaded nanoparticles healthy cell viability increased to 80%.     

pH-Responsive copolymer assemblies for controlled release of doxorubicin

pH-Responsive drug carriers have the potential to provide selective drug release at therapeutic targets including tumors and in acidic intracellular vesicles such as endosomes and lysosomes. We have developed a new approach to the design of acid-sensitive micelles by incorporating hydrophobic acetal groups on the core block of a micelle-forming block copolymer. Hydrolysis of the acetals at mildly acidic pH is designed to reveal polar groups on the core-forming block, thus changing its solubility and disrupting the micelle, triggering drug release. The anticancer drug doxorubicin (DOX) was encapsulated in these pH-sensitive micelles, and the acetal hydrolysis rates and DOX release rates were determined in the pH range of 4.0 to 7.4 and were compared to those of control systems. The micelle disruption was investigated by dynamic light scattering. The in vitro toxicities of the empty and DOX-loaded micelles were determined, and the intracellular fate of the encapsulated DOX was compared to free DOX using fluorescence confocal microscopy.     

Bioreducible micelles self-assembled from amphiphilic hyperbranched multiarm copolymer for glutathione-mediated intracellular drug delivery

A new type of biodegradable micelles for glutathione-mediated intracellular drug delivery was developed on the basis of an amphiphilic hyperbranched multiarm copolymer (H40-star-PLA-SS-PEP) with disulfide linkages between the hydrophobic polyester core and hydrophilic polyphosphate arms. The resulting copolymers were characterized by nuclear magnetic resonance (NMR), Fourier transformed infrared (FTIR), gel permeation chromatography (GPC), and differential scanning calorimeter (DSC) techniques. Benefiting from amphiphilic structure, H40-star-PLA-SS-PEP was able to self-assemble into micelles in aqueous solution with an average diameter of 70 nm. Moreover, the hydrophilic polyphosphate shell of these micelles could be detached under reduction-stimulus by in vitro evaluation, which resulted in a rapid drug release due to the destruction of micelle structure. The glutathione-mediated intracellular drug delivery was investigated against a Hela human cervical carcinoma cell line. Flow cytometry and confocal laser scanning microscopy (CLSM) measurements demonstrated that H40-star-PLA-SS-PEP micelles exhibited a faster drug release in glutathione monoester (GSH-OEt) pretreated Hela cells than that in the nonpretreated cells. Cytotoxicity assay of the doxorubicin-loaded (DOX-loaded) micelles indicated the higher cellular proliferation inhibition against 10 mM of GSH-OEt pretreated Hela cells than that of the nonpretreated ones. As expected, the DOX-loaded micelles showed lower inhibition against 0.1 mM of buthionine sulfoximine (BSO) pretreated Hela cells. These reduction-responsive and biodegradable micelles show a potential to improve the antitumor efficacy of hydrophobic chemotherapeutic drugs.     

Folate-functionalized unimolecular micelles based on a degradable amphiphilic dendrimer-like star polymer for cancer cell-targeted drug delivery

A folate-functionalized degradable amphiphilic dendrimer-like star polymer (FA-DLSP) with a well-defined poly(L-lactide) (PLLA) star polymer core and six hydrophilic polyester dendrons based on 2,2-bis(hydroxymethyl) propionic acid was successfully synthesized to be used as a nanoscale carrier for cancer cell-targeted drug delivery. This FA-DLSP hybrid formed unimolecular micelles in the aqueous solution with a mean particle size of ca. 15 nm as determined by dynamic light scattering and transmission electron microscopy. To study the feasibility of FA-DLSP micelles as a potential nanocarrier for targeted drug delivery, we encapsulated a hydrophobic anticancer drug, doxorubicin (DOX), in the hydrophobic core, and the loading content was determined by UV-vis analysis to be 4 wt %. The DOX-loaded FA-DLSP micelles demonstrated a sustained release of DOX due to the hydrophobic interaction between the polymer core and the drug molecules. The hydrolytic degradation in vitro was monitored by weight loss and proton nuclear magnetic resonance spectroscopy to gain insight into the degradation mechanism of the FA-DLSP micelles. It was found that the degradation was pH-dependent and started from the hydrophilic shell gradually to the hydrophobic core. Flow cytometry and confocal microscope studies revealed that the cellular binding of the FA-DLSP hybrid against human KB cells with overexpressed folate-receptors was about twice that of the neat DLSP (without FA). The in vitro cellular cytotoxicity indicated that the FA-DLSP micelles (without DOX) had good biocompatibility with KB cells, whereas DOX-loaded micelles exhibited a similar degree of cytotoxicity against KB cells as that of free DOX. These results clearly showed that the FA-DLSP unimolecular micelles could be a promising nanosize anticancer drug carrier with excellent targeting property.