嗜神经病毒衍生肽RVG29介导的靶向纳米载药胶束的合成及抗肿瘤活性

将羧基化的水溶性葡聚糖(Dex)与紫杉醇(PTX)化学偶联, 制得载药纳米胶束M(PTX), 再将M(PTX)与嗜神经性病毒衍生肽(RVG29)化学偶联, 得到RVG29靶向的载药纳米胶束M(RVG,PTX). 采用核磁共振氢谱(¹H NMR)测定了Dex-PTX及RVG-Dex-PTX键合物的分子量, 并对2种胶束进行了表征, 考察了2种胶束对肿瘤细胞的抑制效果及细胞凋亡情况, 观察了C₆细胞对荧光标记M(RVG,PTX)和M(PTX)的摄取情况. 结果表明, 羧基化葡聚糖-紫杉醇键合物的分子量约为16500, 紫杉醇的质量约为葡聚糖的20%, RVG29的质量约为葡聚糖的10%. 2种胶束的粒径在45~60 nm之间; M(RVG,PTX)胶束对C₆细胞的抑制作用具有浓度和时间依赖性, 细胞抑制率随着作用时间和药物浓度增加而增加, 且M(RVG,PTX)胶束对C₆细胞的抑制作用强于M(PTX)胶束. 细胞摄取实验结果表明, 与M(PTX)相比, C₆细胞摄取了更多的M(RVG,PTX)胶束. 如果先用游离的RVG29处理C₆细胞, 再进行细胞实验, 则M(RVG,PTX)胶束对C₆细胞生长的抑制作用及被C₆细胞摄取的比率显著降低, 与 M(PTX)相当. 表明靶向载药胶束M(RVG,PTX)中的RVG29保留了游离RVG29的活性, 对C₆细胞依然具有靶向效应, 从而介导了M(RVG,PTX)被C₆细胞的摄取, 增强了对C₆细胞的生长抑制作用. 由于M(RVG,PTX)胶束只使用水溶性葡聚糖作载体, 不涉及疏水高分子链段, 不需要分别制备载药高分子和靶向高分子然后再共组装, 因而制备过程比较简单, 同时具有载药和靶向功能.     

Micelle or polymersome formation by PCL-PEG-PCL copolymers as drug delivery systems

Polymeric micelles and polymersomes may have great potential as the drug delivery vehicles for solubilization of hydrophobic drugs.     

Fluorescent micelles based on star amphiphilic copolymer with a porphyrin core for bioimaging and drug delivery

Star-shaped poly(ε-caprolactone)-b-poly(ethylene oxide) amphiphilic copolymer with a tetrakis-(4-aminophenyl)-terminated porphyrin core was synthesized. Paclitaxel (PTX)-loaded polymeric micelles were prepared by the self-assembly of the star copolymer and in situ encapsulation of PTX. The fluorescent characteristic of the porphyrin moiety allowed the cellular uptake and biodistribution of the PTX-loaded micelles to be monitored by fluorescent imaging. The PTX-loaded micelles can be readily internalized by cancer cells and have a slightly higher cytotoxicity than clinic PTX injection Taxol. In vivo real-time fluorescent imaging revealed that the micelles could accumulate at tumor site via the blood circulation in tumor-bearing mice. In vivo antitumor efficacy examinations indicated that the PTX-loaded micelles had significantly superior efficacy in impeding tumor growth than Taxol and low toxicity to the living mice.     

叶酸修饰星型端氨基PEG-PLGA纳米胶束的制备及肿瘤细胞靶向作用

合成了星型多臂端氨基聚乙二醇(PEG)/聚乳酸-羟基乙酸(PLGA)两亲性嵌段共聚物(4s-PLGA-PEG-NH₂), 并通过核磁共振和凝胶渗滤色谱法对其结构进行表征; 采用溶剂挥发法制备阿霉素载药纳米胶束, 利用EDC缩合法与叶酸偶联, 得到叶酸修饰的星型端氨基PEG-PLGA纳米胶束; 采用动态光散射、 紫外光谱及透射电镜等手段对纳米胶束进行了表征; 对载药纳米胶束在HeLa细胞中的摄取及细胞毒性进行了初步评价. 结果表明, 经叶酸修饰的星型多臂端氨基PEG-PLGA载药纳米胶束可有效提高HeLa细胞的摄取率以及对HeLa细胞的杀伤率, 表明其可作为一类新型的靶向抗肿瘤药物递送载体.     

Syntheses of amphiphilic biodegradable copolymers of poly(ethyl ethylene phosphate) and poly(3-hydroxybutyrate) for drug delivery

Biodegradable and amphiphilic triblock copolymers poly(ethyl ethylene phosphate)-poly(3-hydroxy-butyrate)-poly(ethyl ethylene phosphate) (PEEP-b-PHB-b-PEEP) have been successfully synthesized through ring-opening polymerization. The structures are confirmed by gel permeation chromatography and NMR analyses. Crystallization investigated by X-ray diffraction reveals that the block copolymer with higher content of poly(ethyl ethylene phosphate) (PEEP) is more amorphous, showing decreased crystallizability. The obtained copolymers self-assemble into biodegradable nanoparticles with a core-shell micellar structure in aqueous solution, verified by the probe-based fluorescence measurements and transmission electronic microscopy (TEM) observation. The hydrophobic poly(3-hydroxybutyrate) (PHB) block serves as the core of the micelles and the micelles are stabilized by the hydrophilic PEEP block. The size and size distribution are related to the compositions of the copolymers. Paclitaxel (PTX) has been encapsulated into the micelles as a model drug and a sustained drug release from the micelles is observed. MTT assay also demonstrates that the block copolymers are biocompatible, rendering these copolymers attractive for drug delivery. Supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No.20060358036)     

in vitro biological evaluation of folate-functionalized block copolymer micelles for selective anti-cancer drug delivery

The main objective of this study was to evaluate the ability of folic acid-functionalized diblock copolymer micelles to improve the delivery and uptake of two poorly water-soluble anti-tumor drugs, tamoxifen and paclitaxel, to cancer cells through folate receptor targeting. The diblock copolymer used in this study comprised a hydrophilic poly[2-(methacryloyloxy)ethyl phosphorylcholine] (MPC) block, carrying at the chain end the folate targeting moiety, and a pH-sensitive hydrophobic poly[2-(diisopropylamino)ethyl methacrylate] (DPA) block (FA-MPC-DPA). The drug-loading capacities of tamoxifen- and paclitaxel-loaded micelles were determined by high performance liquid chromatography and the micelle dimensions were determined by dynamic light scattering and transmission electron microscopy. Cell viability studies were carried out on human chronic myelogenous leukaemia (K-562) and colon carcinoma cell lines (Caco-2) in order to demonstrate that drug-loaded FA-MPC-DPA micelles exhibited higher cytotoxicities toward cancer cells than unfunctionalized MPC-DPA micelles. Uptake studies confirmed that folate-conjugated micelles led to increased drug uptake within cancer cells, demonstrating the expected selectivity toward these tumor cells.     

Effect of surface charge of polymeric micelles on in vitro cellular uptake

This work focuses on the interaction between polymeric micelles with different charged surfaces and cancer cells in order to study the influence of surface charge on the in vitro cellular uptake efficiency. The amphiphilic diblock copolymers poly(ε-caprolactone)-b-poly(ethylene oxide) (PCL-b-PEO) with different functional groups at the end of hydrophilic block were synthesized. The functional groups endue the micelles with different charges on the surfaces. The cellular uptake of micelles to T-24 cells (human bladder tumor cells), HepG2 cells (human liver hepatocellular carcinoma cell line) and Hela cells (human epithelial cervical cancer cells) was studied by means of flow cytometer and confocal laser scanning microscopy. The results indicate that the surface charges showed great influence on zeta potential of micelles at different pH values. The in vitro cellular uptake efficiency of micelles with different charged surfaces demonstrated different cellular uptake patterns to three kinds of cancer cells.     

Synthesis of self-assemble pH-responsive cyclodextrin block copolymer for sustained anticancer drug delivery

Well-defined p H-responsive poly(ε-caprolactone)-graft-β-cyclodextrin-graft-poly(2-(dimethylamino)ethylmethacrylate)-co-poly(ethylene glycol) methacrylate amphiphilic copolymers(PCL-g-β-CD-g-P(DMAEMA-co-PEGMA)) were synthesized using a combination of atom transfer radical polymerization(ATRP),ring opening polymerization(ROP) and "click" chemistry.Successful synthesis of polymers was confirmed by Fourier transform infrared spectroscopy(FTIR),proton nuclear magnetic resonance(1H-NMR),and gel permeation chromatography(GPC).Then,the polymers could selfassemble into micelles in aqueous solution,which was demonstrated by dynamic light scattering(DLS) and transmission electron microscopy(TEM).The p H-responsive self-assembly behavior of these copolymers in water was investigated at different p H values of 7.4 and 5.0 for controlled doxorubicin(DOX) release,and these results revealed that the release rate of DOX could be effectively controlled by altering the p H,and the release of drug loading efficiency(DLE) was up to 88%(W/W).CCK-8 assays showed that the copolymers had low toxicity and possessed good biodegradability and biocompatibility,whereas the DOX-loaded micelles remained with high cytotoxicity for He La cells.Moreover,confocal laser scanning microscopy(CLSM) images revealed that polymeric micelles could actively target the tumor site and the efficient intracellular DOX release from polymeric micelles toward the tumor cells further confirmed the anti-tumor effect.The DOX-loaded micelles could easily enter the cells and produce the desired pharmacological action and minimize the side effect of free DOX.These results successfully indicated that p H-responsive polymeric micelles could be potential hydrophobic drug delivery carriers for cancer targeting therapy with sustained release.     

The effect of block copolymer structure on the internalization of polymeric micelles by human breast cancer cells

The objective of this study was to assess the effect of hydrophilic/hydrophobic block chain lengths on the internalization of poly(ethylene oxide)-block-poly(varepsilon-caprolactone) (PEO-b-PCL) micelles by cancer cells. PEO-b-PCL block copolymers with varied PEO and PCL chain lengths were synthesized, assembled to polymeric micelles and loaded with a hydrophobic fluorescent probe (DiI) through a co-solvent evaporation method of physical encapsulation. The slow release of the fluorescent probe from the micellar structure was evidenced following DiI transfer to lipid vesicles. The extent of micellar uptake by cancer cells was investigated through their incubation with MCF-7 cells followed by measurement of the fluorescent emission intensity of DiI (lambda=550 nm) in separated lysed cells. Cellular internalization of polymeric micelles was confirmed by laser scanning microscopy. The mechanism of micellar uptake was investigated by pretreatment of MCF-7 cells with chlorpromazine and cytochalasin B. Encapsulation of DiI in PEO-b-PCL micelles lowered the extent and rate of hydrophobic probe internalization by cancer cells. For polymeric micelles with 5000 gmol(-1) of PCL and varied PEO molecular weights of 2000, 5000 and 13,000 gmol(-1), maximum uptake was observed at a PEO molecular weight of 5000 gmol(-1). For polymeric micelles with 5000 gmol(-1) of PEO and varied PCL molecular weights of 5000, 13,000 and 24,000 gmol(-1), maximum uptake was observed at 13,000 gmol(-1) of PCL. Chlorpromazine reduced the cellular uptake of PEO-b-PCL micelles independent from the block copolymer structure, pointing to the involvement of clathrin mediated endocytosis mechanisms in the uptake of polymeric micelles by cancer cells. Inhibition of cellular uptake of PEO-b-PCL micelles by cytochalasin B, on the other hand, was found to be dependent on the chemical structure of the core/shell forming blocks.     

Preparation of amphiphilic copolymers for covalent loading of paclitaxel for drug delivery system

A novel drug‐polymer conjugate was prepared by the copper‐catalyzed azide–alkyne cycloaddition reaction between an azide‐functional diblock copolymer and an alkyne‐functional paclitaxel (PTX). The well‐defined azide‐functional diblock copolymer, poly(ethylene glycol) (PEG)‐b‐P(OEGEEMA‐co‐AzPMA), was synthesized via the atom transfer radical polymerization of oligo(ethylene glycol) ethyl ether methacrylate (OEGEEMA) and 3‐azidopropyl methacrylate (AzPMA), using PEG‐Br as macroinitiator and CuBr/PMDETA as a catalytic system. The alkyne‐functional PTX was covalently linked to the copolymer via a click reaction, and the loading content of PTX could be easily tuned by varying the feeding ratio. Transmission electron microscopy and dynamic light scattering results indicated that the drug loaded copolymers could self‐assemble into micelles in aqueous solution. Moreover, the drug release behavior of PEG‐b‐P(OEGEEMA‐co‐AzPMA‐PTX) was pH dependent, and the cumulative release amount of PTX were 50.0% at pH 5.5, which is about two times higher than that at pH 7.4. The in vitro cytotoxicity experimental results showed that the diblock copolymer was biocompatible, with no obvious cytotoxicity, whereas the PTX‐polymer conjugate could efficiently deliver PTX into HeLa and SKOV‐3 cells, leading to excellent antitumor activity. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 366–374     

Biomimetic polymersomes as carriers for hydrophilic quantum dots

For polymersomes to achieve their potential as effective delivery vehicles, they must efficiently encapsulate therapeutic agents into either the aqueous interior or the hydrophobic membrane. In this study, cell membrane-mimetic polymersomes were prepared from amphiphilic poly(D,L-lactide)-b-poly(2-methacryloyloxyethylphosphorylcholine) (PLA-b-PMPC) diblock copolymers and were used as encapsulation devices for water-soluble molecules. Thioalkylated zwitterionic phosphorylcholine protected quantum dots (PC@QDs) were chosen as hydrophilic model substrates and successfully encapsulated into the aqueous polymersome interior, as evidenced by transmission electron microscopy (TEM) and flow cytometry. In addition, we also found a fraction of the PC@QDs were bound to both the external and internal surfaces of the polymersome. This interesting immobilization might be due to the ion-pair interactions between the phosphorylcholine groups on the PC@QDs and polymersomes. The experimental encapsulation results support a mechanism of PLA-b-PMPC polymersome formation in which PLA-b-PMPC copolymer chains first form spherical micelles, then worm-like micelles, and finally disk-like micelles which close up to form polymersomes.     

星形PLA-PEG嵌段共聚物胶束的制备与表征

以胆酸为引发剂,用辛酸亚锡催化丙交酯开环聚合合成星型CA-PLA。利用DCC为脱水剂,将不同分子量的端羧基化PEG与星型CA-PLA偶联,合成一系列以胆酸为核的星形两亲性嵌段共聚物,用透析法制备共聚物胶束,并用TEM和DLS研究胶束的性质。合成了分子量为6000和12000的两种CA-PLA,其分子量可以通过胆酸羟基与丙交酯的比例进行控制。将分子量2000和5000的PEG分别与两种CA-PLA偶联,合成了四种星型CA-PLA-PEG嵌段共聚物。共聚物胶束形貌为均匀的球形,粒径为20-40nm,且随共聚物中PLA链段分子量的增加而增大,随PEG链段分子量的增加而减小。临界胶束浓度(CMC)低于同等链段长度的线型PLA-PEG嵌段共聚物胶束。     

A pH-Responsive Zwitterionic Polyurethane Prodrug as Drug Delivery System for Enhanced Cancer Therapy

Numerous nanocarriers with excellent biocompatibilities have been used to improve cancer therapy. However, nonspecific protein adsorption of nanocarriers may block the modified nanoparticles in tumor cells, which would lead to inefficient cellular internalization. To address this issue, pH-responsive polyurethane prodrug micelles with a zwitterionic segment were designed and prepared. The micelle consisted of a zwitterionic segment as the hydrophilic shell and the drug Adriamycin (DOX) as the hydrophobic inner core. As a pH-responsive antitumor drug delivery system, the prodrug micelles showed high stability in a physiological environment and continuously released the drug under acidic conditions. In addition, the pure polyurethane carrier was demonstrated to be virtually non-cytotoxic by cytotoxicity studies, while the prodrug micelles were more efficient in killing tumor cells compared to PEG-PLGA@DOX. Furthermore, the DOX cellular uptake efficiency of prodrug micelles was proved to be obviously higher than the control group by both flow cytometry and fluorescence microscopy. This is mainly due to the modification of a zwitterionic segment with PU. The simple design of zwitterionic prodrug micelles provides a new strategy for designing novel antitumor drug delivery systems with enhanced cellular uptake rates.     

键合紫杉醇的纳米胶束与C6胶质瘤细胞的相互作用

制备了键合紫杉醇(PTX)的聚乙二醇-聚乳酸嵌段共聚物(PEG-PLA/PTX)的纳米胶束, 采用四氮唑(MTT)比色法、流式细胞术、透射电镜及激光共聚焦显微镜等技术, 考察了PEG-PLA/PTX胶束对C6胶质瘤细胞的影响, 包括C6细胞超微结构的变化和细胞周期的改变, 以及纳米颗粒在细胞内的分布, 探讨了PEG-PLA/PTX胶束对肿瘤细胞的作用机理. 结果表明, PEG-PLA/PTX胶束进入到C6细胞内, 聚集于细胞浆中, 通过与细胞核中DNA的作用改变细胞生长的周期, 造成在G2-M期的阻滞, 引起细胞的凋亡. 因此, PEG-PLA/PTX胶束有望用于脑胶质瘤的化疗.     

Comparison of drug delivery properties of PEG-<Emphasis Type="Italic">b</Emphasis>-pdhpc micelles with different compositions

An anti-tumor drug doxorubicin was encapsulated in micelles of poly（ethylene glycol）-b-poly（2,2-dihydroxyl-methyl propylene carbonate）（PEG-b-PDHPC） diblock copolymers.The morphology of both blank micelles and drug loaded micelles was characterized by TEM.The in vitro drug release profiles of micelles were investigated.The cytotoxicity of the micelles was evaluated by incubating with Hela tumor cells and 3T3 fibroblasts.The drug loaded micelles were co-cultured with HepG2 cells to evaluate the in vitro anti-tumor efficacies.The results showed that the mean sizes of both micelles with different copolymer compositions increased after being loaded with drugs.The drug release rate of PEG₄₅-b-PDHPC₃₄ micelles was faster than that of mPEG₁₁₄-b-PDHPC₂₆,micelles.Both of the two block copolymers were non-toxic.The confocal laser scanning microscopy and flow cytometry results showed that both the drug loaded micelles could be internalized efficiently in HepG2 cells.The PEG₄₅-b-PDHPC₃₄ micelles exhibited higher anti-tumor activity comparing to mPEG₁₁₄-b-PDHPC₂₆ micelles.     

Theranostic hyaluronic acid prodrug micelles with aggregation-induced emission characteristics for targeted drug delivery

Theranostic hyaluronic acid (HA) prodrug micelles with pH-responsive drug release and aggregation-induced emission (AIE) properties were prepared by chemical graft of biomimetic phosphorylcholine (PC), anticancer drug doxorubicin (DOX) and AIE fluorogen tetraphenylene (TPE) to the HA backbone. DOX was conjugated to the HA backbone by a hydrazone bond which can be hydrolyzed under acidic environment and result in pH-triggered smart release of DOX. The TPE units with typical AIE characteristics were applied for real time drug tracking in cancer cells. The HA-based prodrugs could self-assemble into micelles in aqueous solution as confirmed by the dynamic light scattering (DLS) and transmission electron microscopy (TEM). The intracellular distribution of HA prodrug micelles could be clearly observed by fluorescence microscopy based on the strong fluorescence of TPE. Moreover, after treated with the micelles, stronger fluorescence of TPE in CD44 overexpressed MDA-MB-231 cancer cells was observed, compared to the CD44 negative cell line, NIH3T3 cells, suggesting efficient cell uptake of HA prodrug micelles by receptor-mediated endocytosis. The cell viability results indicated that the prodrug micelles could inhibit the proliferation of the cancer cells effectively. Such pH-triggered theranostic drug delivery system with AIE features can provide a new platform for targeted and image-guided cancer therapy.     

Biomimetic pH/redox dual stimuli‐responsive zwitterionic polymer block poly(L‐histidine) micelles for intracellular delivery of doxorubicin into tumor cells

A series of pH/redox dual stimuli‐responsive poly(2‐methacryloyloxyethyl phosphorylcholine)₂₅‐block‐poly(l ‐histidine)_n (p[MPC])₂₅‐b‐p[His]_n, n = 20, 35, 50, and 75) copolymers consisting of a pH‐responsive p(His)_n block and a biocompatible phospholipid analog p(MPC) block connected by a redox‐responsive disulfide linker have been synthesized. The block copolymers are self‐assembled into uniform micelles (～100 nm) in which doxorubicin (Dox) is efficiently encapsulated. The in vitro release profile shows an enhanced release of Dox at low pH (5.0) in 10 mM glutathione (GSH). The in vitro cell viability assays performed using various cell lines show that the blank hybrid micelles have no acute or intrinsic toxicity. A pH‐dependent cytotoxicity is observed with the Dox‐loaded micelles, especially at pH 5.0. Moreover, confocal microscopy images and flow cytometry results show the pH‐dependent cellular uptake of Dox‐loaded micelles. Therefore, the Dox‐loaded micelles can be considered a good candidate for cancer therapy. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2061–2070     

The intragastrointestinal fate of paclitaxel-loaded micelles: Implications on oral drug delivery

The goal of the present study is to elucidate the intragastrointestinal fate of micellar delivery systems by monitoring fluorescently labeled different micelles and the model drug paclitaxel (PTX). Both in vitro and ex vivo leakage studies showed fast PTX release in fluids while micelles remained intact, except in fed-state simulated intestinal fluid and fasted-state pig intestinal fluid, thus referring to the intact absorption of micelles and PTX leakage in the gastrointestinal tract with d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) micelles showing higher stability than other micelles. All groups of micelles were absorbed intact in Caco-2 and Caco-2/HT29-MTX cell models and the absorption of TPGS micelles was found to be higher than other micelles. The transport of the micelles across Caco-2/Raji (1.6%–3.5%), Caco-2 (0.8%–1%), and Caco-2/HT29-MTX (0.58%–1%) cell monolayers further verified the absorption of micelles and their subsequent transport; however, more TPGS micelles transported across cell monolayers than other groups. Moreover, the histological examination also confirmed that micelles entered the enterocytes and were transported to basolateral tissues and TPGS showed the stronger ability of penetration than other groups. Thus, these results are succinctly presenting the absorption of intact micelles in GIT confirmed by imaging evidence with prior leakage of the drug, uptake by enterocytes and the transport of micelles that survive the digestion by enterocytes and mainly by microfold cells in material nature dependent way with TPGS showing better results than other groups. In conclusion, these results identify the mechanism by which the gastrointestinal tract processes micelles and point to the likely use of this approach in the design of micelles-based therapies.     

Histology and antitumor activity study of PTX-loaded micelle,a fluorescent drug delivery system prepared by PEG-TPP

We synthesized PEG-TPP as carrier to encapsulate paclitaxel(PTX) in the form of micelles to overcome its water-solubility problem. PTX-loaded micelles possess a-week stability and appropriate particle size(152.1 ±1.2 nm) which is beneficial for enhanced permeability and retention(EPR) effect. Strong pH dependence of PTX releasing from micelles is verified by in vitro release study. At cellular level, PTXloaded micelles can target mitochondria effectively which may results a better cytotoxicity of micelles(especially IC50= 0.123 ± 0.035 mmol/L of micelles and 0.298 ± 0.067 mmol/L of PTX alone on MCF-7 cells). The fluorescence distributions of both isolated and sliced organs show that the micelles can effectively target tumors. Moreover, we further prove the enhanced therapeutic effects of micelles in tumor-bearing mice comparing with PTX alone. The results show that the biodegradable drug delivery system prepared by PEG-TPP can overcome the poor solubility of paclitaxel and improve its tumor targeting and antitumor activity.     

An optimized RGD-decorated micellar drug delivery system for albendazole for the treatment of ovarian cancer: from RAFT polymer synthesis to cellular uptake

Block copolymers were prepared via RAFT polymerization with P(PEGMEMA) as the hydrophilic block to form micelles for the controlled delivery of ABZ. The group contribution method was used to estimate the partial solubility parameters for ABZ and various polymers as potential core‐forming block to achieve optimum compatibility. Different ratios between MMA and LMA, a non‐compatible monomer, were prepared. Cytotoxicity tests revealed a high toxicity of the ABZ‐loaded micelle resulting in 80% cell deaths at a micelle concentration of 10 µg · mL^?1. Cellular uptake of micelles has been studied using fluorescently labeled micelles, showing that a large fraction of micelles is readily taken up by OVCAR‐3 cells. RGD‐conjugated micelles were prepared and showed an increased cellular uptake.