pH敏感型mPEG-Hz-PLA聚合物纳米载药胶束的制备

以合成的含有腙键的聚乙二醇大分子(mPEG-Hz-OH)为引发剂,以丙交酯为单体引发开环聚合反应,并通过调整投料比,制备出3种不同分子量的含腙键的生物可降解嵌段聚合物(mPEG-Hz-PLA).将腙键引入到聚合物的骨架中,以此构建聚合物胶束并作为pH敏感型纳米药物载体.制备的pH敏感型胶束的CMC值等于或低于5.46×10-4 mg/m L,DLS和TEM显示粒径均小于100 nm,且粒径分布均匀.非pH敏感型胶束在不同pH下的粒径变化不明显,而pH敏感型胶束在酸性环境下(pH=4.0和pH=5.0)胶束粒径出现了明显变化.以阿霉素为模型药物制备了pH敏感型载药胶束,其粒径比空白胶束大(100~200 nm),且粒径分布均匀.药物释放实验表明pH敏感型载药胶束随着释放介质pH降低累积释药量增高.MTT实验表明空白胶束对HeLa细胞和RAW264.7细胞几乎没有抑制作用,而载阿霉素的胶束对2种细胞的抑制作用都随着剂量的增大和时间的延长而增强.     

Dendritic polyurethane-based prodrug as unimolecular micelles for precise ultrasound-activated localized drug delivery

Ultrasound has been recognized as an exciting tool to enhance the therapeutic efficacy in tumor chemotherapy owing to the triggered drug release, facilitated intracellular drug delivery, and improved spatial precision. Aiming for a precise localized drug delivery, novel dendritic polyurethane-based prodrug (DOX-DPU-PEG) was fabricated with a drug content of 18.9% here by conjugating DOX onto the end groups of the functionalized dendritic polyurethane via acid-labile imine bonds. It could easily form unimolecular micelles around 38 nm. Compared with the non-covalently drug-loaded unimolecular micelles (DOX@Ph-DPU-PEG), they showed excellent pH/ultrasound dual-triggered drug release performance, with drug leakage of only 4% at pH 7.4, but cumulative release of 14% and 88% at pH 5.0 without and with ultrasound, respectively. The ultrasound responsiveness was attributed to the unique strawberry-shaped topological structure of the DOX-DPU-PEG, in which DOX was embedded in the skin layer of the hydrophobic DPU cores. With ultrasound, the DOX-DPU-PEG unimolecular micelles possessed enhanced tumor growth inhibition than free DOX but showed no obvious cytotoxicity on the tumor cells without ultrasound. Such feature makes them promising potential for precise localized drug delivery.     

Dual‐responsive crosslinked micelles of a multifunctional graft copolymer for drug delivery applications

A novel multifunctional amphiphilic graft copolymer has been synthesized consisting of a biodegradable poly(l ‐aspartic acid) backbone that was decorated by water‐soluble poly(ethylene glycol) (PEG) and pH‐responsive poly(N,N‐diethylaminoethyl methacrylate) (PDEAEMA) side‐chains as well as thiol pendant groups. This graft copolymer together with doxorubicin (DOX) formed micelles in water at pH = 10.0 with PDEAEMA and DOX acting as the core and PEG serving as the micellar corona. Upon oxidation, the thiol groups dimerized to form disulfide bonds, thus “locking in” the micellar structure. These crosslinked micelles expanded as the pH was decreased from 7.4 to 5.0 or upon the addition, at pH = 7.4, of glutathione (GSH), a thiol‐containing oligopeptide that is present in cancerous cells and cleaves disulfide bonds. At pH = 5.0, GSH addition triggered the disassembly of the micelles. The expansion and disassembly of the micelles have been determined via in vitro experiments to evaluate their DOX release behavior. More importantly, the graft copolymer micelles could enter cells by means of endocytosis and deliver DOX to the nuclei of ovarian cancer BEL‐7402 cells. Thus, this polymer and its micelles are promising candidates for drug delivery applications. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 1536–1546     

pH‐sensitive carbon quantum dots−doxorubicin nanoparticles for tumor cellular targeted drug delivery

A kind of pH‐responsive carbon quantum dots?doxorubicin nanoparticles drug delivery platform (D‐Biotin/DOX‐loaded mPEG‐OAL/N‐CQDs) was designed and synthesized. The system consists of fluorescent carbon dots as cross‐linkers, and D‐Biotin worked as targeting groups, which made the system have a pH correspondence, doxorubicin hydrochloride (DOX) as the target drug, oxidized sodium alginate (OAL) as carrier materials. Ultraviolet (UV)‐Vis spectrum showed that the drug‐loading rate of DOX is 10.5%, and the drug release in vitro suggested that the system had a pH response and tumor cellular targeted, the drug release rate is 65.6% at the value of pH is 5.0, which is much higher than that at the value of pH is 7.4. The cytotoxicity test and laser confocal fluorescence imaging showed that the synthesized drug delivery system has high cytotoxicity to cancer cells, and the drug‐loaded nanoparticles could enter the cells through endocytosis.     

Drug Self‐Delivery Systems Based on Hyperbranched Polyprodrugs towards Tumor Therapy

Amphiphilic hyperbranched polyprodrugs (DOX‐S‐S‐PEG) with drug repeat units in hydrophobic core linked by disulfide bonds were developed as drug self‐delivery systems for cancer therapy. The hydroxyl groups and the amine group in doxorubicin (DOX) were linked by 3,3′‐dithiodipropanoic acid as hydrophobic hyperbranched cores, then amino‐terminated polyethylene glycol monomethyl ether (mPEG‐NH₂) as hydrophilic shell was linked to hydrophobic cores to form amphiphilic and glutathione (GSH)‐responsive micelle of hyperbranched polyprodrugs. The amphiphilic micelles can be disrupted under GSH (1 mg mL^?1) circumstance. Cell viability of A549 cells and 293T cells was evaluated by CCK‐8 and Muse Annexin V & Dead Cell Kit. The disrupted polyprodrugs maintained drug activity for killing tumor cells. Meanwhile, the undisrupted polyprodrugs possessed low cytotoxicity to normal cells. The cell uptake experiments showed that the micelles of DOX‐S‐S‐PEG were taken up by A549 cells and distributed to cell nuclei. Thus, the drug self‐delivery systems with drug repeat units in hydrophobic cores linked by disulfide bonds showed significant special advantages: 1) facile one‐pot synthesis; 2) completely without toxic or non‐degradable polymers; 3) DOX itself functions as fluorescent labeled molecule and self‐delivery carrier; 4) drug with inactive form in hyperbranched cores and low cytotoxicity to normal cells. These advantages make them excellent drug self‐delivery systems for potential high efficient cancer therapy.     

荧光标记pH敏感胶束的制备及其药物控释

利用原子转移自由基聚合方法（ATRP）合成了pH敏感的两亲性嵌段共聚物mPEG-b-PDPA_n（聚合度n=100-200）及荧光修饰的嵌段聚合物异硫氰酸荧光素-聚乙二醇-聚N,N-二异丙胺基甲基丙烯酸乙酯（FITCPEG₄₅-PDPA₁₀₀）。采用溶剂挥发的方法制备胶束,此胶束呈现均一的球形分布,平均粒径180-240 nm（0.3 mg·mL^-1）。以阿霉素（DOX）为模拟药物,其胶束载药量约11%（w,质量分数）左右,外环境pH对载药胶束的粒径和体外释放行为有显著影响。在弱酸环境下,胶束核质子化发生膨胀甚至解体,在2-3 h内药物可释放80%左右。体外毒性试验表明,空白胶束与人类肝癌细胞（Huh7）有良好的生物相容性。同时,与此细胞共同孵育5 h的荧光聚合物胶束体现了较好的转染效果。因此,这类荧光标记胶束可能会为实时跟踪化疗药物的输送或分布打开新的视角。     

Grafted copolymer micelles with pH triggered charge reversibility for efficient doxorubicin delivery

The instability and premature charge reversal at pH 7.4 have become the major limitations of charge‐reversal delivery systems. To address this problem, graft copolymer of poly(butylene succinate)‐g‐cysteamine‐bi‐poly(ethylene glycol) (PBS‐g‐CS‐bi‐PEG, bi = benzoic imine bond) was designed and synthesized through facile thiol‐ene click reaction and subsequent Schiff's base reaction. Then, PBS‐g‐CS‐bi‐PEG and carboxyl‐functionalized polyester of poly(butylene succinate)‐g‐3‐mercaptopropionic acid (PBS‐g‐MPA) co‐assemble in aqueous solution to give PEG shell‐sheddable charge‐reversal micelles with sizes of 85–103 nm and low polydispersity of 0.11–0.12. Interestingly, the PBS‐g‐MPA/CS‐bi‐PEG micelles could sensitively and arbitrarily switch their surface charges between negative and positive status in response to pH fluctuation via reversible protonation and deprotonation of carboxyl and amino groups, which endows the desired stability of co‐assembly micelles either during long‐term storage or under physiological conditions. Doxorubicin (DOX) was loaded into PBS‐g‐MPA/CS‐bi‐PEG micelles with a high drug‐loading content of 10.2% and entrapment efficiency of 68% as a result of electrostatic attraction. In vitro release studies revealed that less than 25% of DOX was released within 24 h in the environment mimicking the physiological condition, whereas up to 81% of DOX was released in 24 h under weak‐acid condition resembling microenvironment in endosome/lysosome. In vitro cytotoxicity study suggested that blank PBS‐g‐MPA/CS‐bi‐PEG micelles possessed excellent biocompatibility, while DOX‐loaded PBS‐g‐MPA/CS‐bi‐PEG micelles showed significant cytotoxicity with half‐maximal inhibitory concentration (IC₅₀) of 1.55–1.67 μg DOX equiv/mL. This study provides a facile and effective approach for the preparation of novel charge‐reversal micelles with switchable charges and excellent biocompatibility, which are highly promising to be used as safe nanocarriers for efficient intracellular drug delivery. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2036–2046     

Nucleobase‐Functionalized Supramolecular Micelles with Tunable Physical Properties for Efficient Controlled Drug Release

Complementary nucleobase‐functionalized polymeric micelles, a combination of adenine‐thymine (A‐U) base pairs and a blend of hydrophilic–hydrophobic polymer pairs, can be used to construct 3D supramolecular polymer networks; these micelles exhibit excellent self‐assembly ability in aqueous solution, rapid pH‐responsiveness, high drug loading capacity, and triggerable drug release. In this study, a multi‐uracil functionalized poly(ε‐caprolactone) (U‐PCL) and adenine end‐capped difunctional oligomeric poly(ethylene glycol) (BA‐PEG) are successfully developed and show high affinity and specific recognition in solution owing to dynamically reversible A‐U‐induced formation of physical cross‐links. The U‐PCL/BA‐PEG blend system produces supramolecular micelles that can be readily adjusted to provide the desired critical micellization concentration, particle size, and stability. Importantly, in vitro release studies show that doxorubicin (DOX)‐loaded micelles exhibit excellent DOX‐encapsulated stability under physiological conditions. When the pH value of the solution is reduced from 7.4 to 5.0, DOX‐loaded micelles can be rapidly triggered to release encapsulated DOX, suggesting these polymeric micelles represent promising candidate pH‐responsive nanocarriers for controlled‐release drug delivery and pharmaceutical applications.

     

Synthesis and characterization of biodegradable pH and reduction dual‐sensitive polymeric micelles for doxorubicin delivery

Novel pH and reduction dual‐sensitive biodegradable polymeric micelles for efficient intracellular delivery of anticancer drugs were prepared based on a block copolymer of methyloxy‐poly(ethylene glycol)‐b‐poly[(benzyl‐l ‐aspartate)‐co‐(N‐(3‐aminopropyl) imidazole‐l ‐aspartamide)] [mPEG‐SS‐P(BLA‐co‐APILA), MPBA] synthesized by a combination of ring‐opening polymerization and side‐chain reaction. The pH/reduction‐responsive behavior of MPBA was observed by both dynamic light scattering and UV–vis experiments. The polymeric micelles and DOX‐loaded micelles could be prepared simply by adjusting the pH of the polymer solution without the use of any organic solvents. The drug release study indicated that the DOX‐loaded micelles showed retarded drug release in phosphate‐buffered saline at pH 7.4 and a rapid release after exposure to weakly acidic or reductive environment. The empty micelles were nontoxic and the DOX‐loaded micelles displayed obvious anticancer activity similar to free DOX against HeLa cells. Confocal microscopy observation demonstrated that the DOX‐loaded MPBA micelles can be quickly internalized into the cells, and effectively deliver the drugs into nuclei. Thus, the pH and reduction dual‐responsive MPBA polymeric micelles are an attractive platform to achieve the fast intracellular release of anticancer drugs. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1771–1780     

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.     

Preparation and characteristics of linoleic acid-grafted chitosan oligosaccharide micelles as a carrier for doxorubicin

The linoleic acid (LA)-grafted chitosan oligosaccharide (CSO) (CSO-LA) was synthesized in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), and the effects of molecular weight of CSO and the charged amount of LA on the physicochemical properties of CSO-LA were investigated, such as CMC, graft ratio, size, zeta potential. The results showed that these chitosan derivatives were able to self-assemble and form spherical shape polymeric micelles with the size range of 150.7–213.9 nm and the zeta potential range of 57.9–79.9 mV, depending on molecular weight of CSO and the charged amount of LA. Using doxorubicin (DOX) as a model drug, the DOX-loaded CSO-LA micelles were prepared by dialysis method. The drug encapsulation efficiencies (EE) of DOX-loaded CSO-LA micelles were as high as about 75%. The sizes of DOX-loaded CSO-LA micelles with 20% charged DOX (relating the mass of CSO-LA) were near 200 nm, and the drug loading (DL) capacity could reach up to 15%. The in vitro release studies indicated that the drug release from the DOX-loaded CSO-LA micelles was reduced with increasing the graft ratio of CSO-LA, due to the enhanced hydrophobic interaction between hydrophobic drug and hydrophobic segments of CSO-LA. Moreover, the drug release rate from CSO-LA micelles was faster with the drug loading. These data suggested the possible utilization of the amphiphilic micellar chitosan derivatives as carriers for hydrophobic drugs for improving their delivery and release properties.     

Comparative study of paclitaxel physically encapsulated in and chemically conjugated with PEG‐PLA

Paclitaxel‐loaded poly(ethylene glycol)‐b‐poly(l ‐lactide (LA)) (PEG‐PLA) micelles were prepared by two methods. One is physical encapsulation of paclitaxel in micelles composed of a PEG‐PLA block copolymer and the other is based on a PEG‐PLA–paclitaxel conjugate, abbreviated as “conjugate micelles”. Their physicochemical characteristics, e.g. critical micelle concentration (CMC), morphology, and micelle size distribution were then evaluated by means of fluorescence spectroscopy, scanning electron microscopy (SEM), and dynamic light scattering (DLS). The results show that the CMC of PEG‐PLA–paclitaxel and PEG‐PLA are 6.31 × 10^?4 and 1.78 × 10^?3 g L^?1, respectively. Both micelles assume a spherical shape with comparable diameters and have unimodal size distribution. Moreover, invitro drug delivery behavior was studied by high performance liquid chromatography (HPLC). The antitumor activity of the paclitaxel‐loaded micelles against human liver cancer H7402 cells was evaluated by 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) method. The conjugate micelles show a lower burst release during the initial stage and higher accumulative release amount of paclitaxel after a period of time while the encapsulated ones behave in the opposite way. Both the paclitaxel‐loaded micelles showed comparable anticancer efficacy with the free drug. Copyright © 2008 John Wiley & Sons, Ltd.     

N‐Boc‐Histidine‐Capped PLGA‐PEG‐PLGA as a Smart Polymer for Drug Delivery Sensitive to Tumor Extracellular pH

A pH‐sensitive polymer was synthesized by introducing the N‐Boc‐histidine to the ends of a PLGA‐PEG‐PLGA block copolymer. The synthesized polymer was confirmed to be biodegradable and biocompatible, well dissolved in water and forming micelles above the CMC. DOX was employed as a model anticancer drug. In vitro drug release from micelles of N‐Boc‐histidine‐capped PLGA‐PEG‐PLGA exhibited significant difference between pH = 6.2 and pH = 7.4, whereas DOX release from micelles composed of un‐capped virgin polymers was not significantly sensitive to medium pH. Uptake of DOX from micelles of the new polymer into MDA‐MB‐435 solid tumor cells was also observed, and pH sensitivity was confirmed. Hence, the N‐Boc‐histidine capped PLGA‐PEG‐PLGA might be a promising material for tumor targeting.

     

具有pH-响应性的聚天冬氨酸类载药胶束的制备和释放能力研究

通过大分子引发剂ω-氨基-α-甲氧基聚乙二醇引发N-羧基-α-氨基环内酸酐开环聚合和水合肼侧基改性,制备了一系列聚乙二醇-聚氨基酸类三嵌段共聚物.其中聚氨基酸链段包括具有酰肼基的聚天冬氨酸衍生物(PAHy),以及疏水性的聚丙氨酸链段.引入具有pH响应性的腙键键合阿霉素,利用键合阿霉素与游离阿霉素之间的π-π叠合作用,在聚合物自组装形成胶束过程中通过化学键合+物理包埋的方式充分负载药物.该胶束以聚丙氨酸链段为核心,以PEG链段为冠层,以PAHy链段为包裹药物的壳层.载药胶束的粒径在170 nm左右.研究不同pH值条件下载药胶束的药物释放能力,随环境pH值的降低药物的释放速率显著增加.     

Micellar Nanocarriers Assembled from Doxorubicin‐Conjugated Amphiphilic Macromolecules (DOX–AM)

Amphiphilic macromolecules (AMs) have unique branched hydrophobic domains attached to linear PEG chains. AMs self‐assemble in aqueous solution to form micelles that are hydrolytically stable in physiological conditions (37 °C, pH 7.4) over 4 weeks. Evidence of AM biodegradability was demonstrated by complete AM degradation after 6 d in the presence of lipase. Doxorubicin (DOX) was chemically conjugated to AMs via a hydrazone linker to form DOX–AM conjugates that self‐assembled into micelles in aqueous solution. The conjugates were compared with DOX‐loaded AM micelles (i.e., physically loaded DOX) on DOX content, micellar sizes and in vitro cytotoxicity. Physically encapsulated DOX loading was higher (12 wt.‐%) than chemically bound DOX (6 wt.‐%), and micellar sizes of DOX‐loaded AMs (≈16 nm) were smaller than DOX–AMs (≈30 nm). In vitro DOX release from DOX–AM conjugates was faster at pH 5.0 (100%) compared to pH 7.4 (78%) after 48 h, 37 °C. Compared to free DOX and physically encapsulated DOX, chemically bound DOX had significantly higher cytotoxicity at 10^?7 M DOX dose against human hepatocellular carcinoma cells after 72 h. Overall, DOX–AM micelles showed promising characteristics as stable, biodegradable DOX nanocarriers.

     

Mesoporous silica nanoparticles for 19F magnetic resonance imaging,fluorescence imaging,and drug delivery

Multifunctional mesoporous silica nanoparticles (MSNs) are good candidates for multimodal applications in drug delivery, bioimaging, and cell targeting. In particular, controlled release of drugs from MSN pores constitutes one of the superior features of MSNs. In this study, a novel drug delivery carrier based on MSNs, which encapsulated highly sensitive ¹⁹F magnetic resonance imaging (MRI) contrast agents inside MSNs, was developed. The nanoparticles were labeled with fluorescent dyes and functionalized with small molecule-based ligands for active targeting. This drug delivery system facilitated the monitoring of the biodistribution of the drug carrier by dual modal imaging (NIR/¹⁹F MRI). Furthermore, we demonstrated targeted drug delivery and cellular imaging by the conjugation of nanoparticles with folic acid. An anticancer drug (doxorubicin, DOX) was loaded in the pores of folate-functionalized MSNs for intracellular drug delivery. The release rates of DOX from the nanoparticles increased under acidic conditions, and were favorable for controlled drug release to cancer cells. Our results suggested that MSNs may serve as promising ¹⁹F MRI-traceable drug carriers for application in cancer therapy and bio-imaging.     

Synthesis,self-assembly,and pH-responsive drug release of PHMEMA-PEG-PHMEMA ABA triblock copolymers

Abstract

A series of tertiary amine containing PHMEMA-PEG-PHMEMA ABA triblock copolymers were synthesized by atom transfer radical polymerization (ATRP) using bromine-capped poly(ethylene glycol) (Br-PEG-Br) and 2-(hexamethyleneimino)ethyl methacrylate (HMEMA) as macro-initiator and monomers, respectively. The chemical structures and molecular weights of triblock copolymers were characterized by ¹H NMR and gel permeation chromatography (GPC). The self-assembly behaviors of copolymers in different pH conditions were studied by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Triblock copolymers self-assembled into micelles in water (pH 7.4) and the micelles disassembled at acidic pH (pH 5.0). Anticancer drug doxorubicin (DOX) was used as a drug model and physically encapsulated into polymeric micelles. The drug release of DOX-loaded polymeric micelles was pH-responsive; the drug-loaded micelles that had higher contents of tertiary amine in polymer pendant groups showed faster release speed. In addition, the drug-loaded micelles showed excellent inhibition efficacy against HeLa cells in vitro.     

Amphiphilic block poly(propylene carbonate)‐block‐allyloxypolyethyleneglycol copolymer based shell cross‐linked micelles for controlled release of drug

Amphiphilic block poly(propylene carbonate)‐block‐allyloxypolyethyleneglycol (PPC‐b‐APEG) copolymer was synthesized by the click chemistry, and its structure were characterized. PPC‐b‐APEG can self‐assemble into micelles without emulsifier in water. Shell cross‐linked micelles were obtained by the reaction of the allyloxy groups, which were exposed on the outer of the PPC‐b‐APEG micelles, and N‐vinylpyrrolidone (NVP). The morphology and size of the micelles before and after cross‐link reactions were characterized. The research result shows that the shell cross‐linking could improve the stability of micelles. The particle size of uncross‐linked micelle was about 800 nm. The size of cross‐linked micelles increased with increasing amount of cross‐linking degree. To better evaluate the release behavior of PPC‐b‐PEG copolymer, doxorubicin (DOX)‐loaded micelles were synthesized using DOX as the model drug. Results showed that the DOX releasing rate decreased with increasing of NVP. The shell cross‐linking do decrease the burst release behaviours of DOX and reduce the DOX release rate.     

Hyperbranched copolymer micelles as delivery vehicles of doxorubicin in breast cancer cells

Four types of drug nanoparticles (NPs) based on amphiphilic hyperbranched block copolymers were developed for the delivery of the chemotherapeutic doxorubicin (DOX) to breast cancer cells. These carriers have their hydrophobic interior layer composed of the hyperbranched aliphatic polyester, Boltorn^® H30 or Boltorn^® H40, that are polymers of poly 2,2‐bis (methylol) propionic acid (bis‐MPA), while the outer hydrophilic shell was composed of about 5 poly(ethylene glycol) (PEG) segments of 5 or 10 kDa molecular weight. A chemotherapeutic drug DOX, was further encapsulated in the interior of these polymer micelles and was shown to exhibit a controlled release profile. Dynamic light scattering and transmission electron microscopy analysis confirmed that the NPs were uniformly sized with a mean hydrodynamic diameter around 110 nm. DOX‐loaded H30‐PEG10k NPs exhibited controlled release over longer periods of time and greater cytotoxicity compared with the other materials developed against our tested breast cancer cell lines. Additionally, flow cytometry and confocal scanning laser microscopy studies indicated that the cancer cells could internalize the DOX‐loaded H30‐PEG10k NPs, which contributed to the sustained drug release, and induced more apoptosis than free DOX did. These findings indicate that the H30‐PEG10k NPs may offer a very promising approach for delivering drugs to cancer cells. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

NIR-triggered drug delivery system based on phospholipid coated ordered mesoporous carbon for synergistic chemo-photothermal therapy of cancer cells

Chemo-photothermal treatment is one of the most efficient strategies for cancer therapy. However, traditional drug carriers without near-infrared absorption capacity need to be loaded with materials behaving photothermal properties, as it results in complicated synthesis process, inefficient photothermal effects and hindered NIR-mediated drug release. Herein we report a facile synthesis of a polyethylene glycol (PEG) linked liposome (PEG-liposomes) coated doxorubicin (DOX)-loaded ordered mesoporous carbon (OMC) nanocomponents (PEG-LIP@OMC/DOX) by simply sonicating DOX and OMC in PEG-liposomes suspensions. The as-obtained PEG-LIP@OMC/DOX exhibits a nanoscale size (600±15 nm), a negative surface potential (-36.70 mV), high drug loading (131.590 mg/g OMC), and excellent photothermal properties. The PEG-LIP@OMC/DOX can deliver loaded DOX to human MCF-7 breast cancer cells (MCF-7) and the cell toxicity viability shows that DOX unloaded PEG-LIP@OMC has no cytotoxicity, confirming the PEG-LIP@OMC itself has excellent biocompatibility. The NIR-triggered release studies demonstrate that this NIR-responsive drug delivery system enables on-demand drug release. Furthermore, cell viability results using human MCF-7 cells demonstrated that the combination of NIR-based hyperthermal therapy and triggered chemotherapy can provide higher therapeutic efficacy than respective monotherapies. With these excellent features, we believe that this phospholipid coating based multifunctional delivery system strategy should promote the application of OMC in nanomedical applications.