Cancer‐associated pH‐responsive tetracopolymeric micelles composed of poly(ethylene glycol)‐b‐poly(L‐histidine)‐b‐poly(L‐lactic acid)‐b‐poly(ethylene glycol)

To create a novel vector for specifically delivering anticancer therapy to solid tumors, we used diafiltration to synthesize pH‐sensitive polymeric micelles. The micelles, formed from a tetrablock copolymer [poly(ethylene glycol)‐b‐poly(L ‐histidine)‐b‐poly(L ‐lactic acid)‐b‐poly(ethylene glycol)] consisted of a hydrophobic poly(L ‐histidine) (polyHis) and poly(L ‐lactic acid) (PLA) core and a hydrophilic poly(ethylene glycol) (PEG) shell, in which we encapsulated the model anticancer drug doxorubicin (DOX). The robust micelles exhibited a critical micellar concentration (CMC) of 2.1–3.5 µg/ml and an average size of 65–80 nm pH 7.4. Importantly, they showed a pH‐dependent micellar destabilization, due to the concurrent ionization of the polyHis and the rigidity of the PLA in the micellar core. In particular, the molecular weight of PLA block affected the ionization of the micellar core. Depending on the molecular weight of the PLA block, the micelles triggering released DOX at pH 6.8 (i.e. cancer acidic pH) or pH 6.4 (i.e. endosomal pH), making this system a useful tool for specifically treating solid cancers or delivering cytoplasmic cargo in vivo. Copyright © 2008 John Wiley & Sons, Ltd.     

Calcium Phosphate‐Reinforced Photosensitizer‐Loaded Polymer Nanoparticles for Photodynamic Therapy

Calcium phosphate‐reinforced photosensitizer‐loaded polymer nanoparticles have been developed for photodynamic therapy. Chlorin e6 (Ce6)‐loaded core–shell–corona polymer micelles of poly(ethylene glycol)‐b‐poly(L ‐aspartic acid)‐b‐poly(L ‐phenylalanine) ( PEG-PAsp-PPhe ) were employed as template nanoparticles for mineralization with calcium phosphate (CaP). CaP deposition was performed by the electrostatic localization of calcium ions at the anionic PAsp middle shells and the subsequent addition of phosphate anions. CaP‐reinforced nanoparticles exhibited enhanced stability. The CaP mineral layer effectively inhibited Ce6 release from the Ce6‐loaded mineralized nanoparticles (Ce6‐NP‐CaP) at physiological pH value. At an acidic endosomal pH value of 5.0, Ce6 release was enhanced, owing to rapid dissolution of the CaP minerals. Upon irradiation of Ce6‐NP‐CaP‐treated MCF‐7 breast‐tumor cells, the cell viability dramatically decreased with increasing irradiation time. The phototoxicity of Ce6‐NP‐CaP was much higher than that of free Ce6. Non‐invasive optical‐imaging results indicated that Ce6‐NP‐CaP exhibited enhanced tumor specificity compared with free Ce6 and Ce6‐loaded non‐mineralized polymer nanoparticles (Ce6‐NP).     

Cyclodextrin‐overhanging hyperbranched core‐double‐shell miktoarm architectures: Synthesis and gradient stimuli‐responsive properties

We report the synthesis and gradient stimuli‐responsive properties of cyclodextrin‐overhanging hyperbranched core‐double‐shell miktoarm architectures. A ionic hyperbranched poly(β‐cyclodextrin) (β‐CD) core was firstly synthesized via a convenient “A₂+B₃” approach. Double‐layered shell architectures, composed of poly(N‐isopropyl acrylamide) (PNIPAm) and poly(N,N‐dimethylaminoethyl methacrylate) (PDMAEMA) miktoarms as the outermost shell linked to poly(N,N‐diethylaminoethyl methacrylate) (PDEAEMA) homoarms which form the inner shell, were obtained by a sequential atom transfer radical polymerization (ATRP) and parallel click chemistry from the modified hyperbranched poly(β‐CD) macroinitiator. The combined characterization by ¹H NMR, ¹³C NMR, ¹H‐²⁹Si heteronuclear multiple‐bond correlation (HMBC), FTIR and size exclusion chromatography/multiangle laser light scattering (SEC/MALLS) confirms the remarkable hyperbranched poly(β‐CD) core and double‐shell miktoarm architectures. The gradient triple‐stimuli‐responsive properties of hyperbranched core‐double‐shell miktoarm architectures and the corresponding mechanisms were investigated by UV–vis spectrophotometer and dynamic light scattering (DLS). Results show that this polymer possesses three‐stage phase transition behaviors. The first‐stage phase transition comes from the deprotonation of PDEAEMA segments at pH 9–10 aqueous solution under room temperature. The confined coil‐globule conformation transition of PNIPAm and PDMAEMA arms gives rise to the second‐stage hysteretic cophase transition between 38 and 44 °C at pH 10. The third‐stage phase transition occurs above 44 °C at pH = 10 attributed to the confined secondary conformation transition of partial PDMAEMA segments. This cyclodextrin‐overhanging hyperbranched core‐double‐shell miktoarm architectures are expected to solve the problems of inadequate functionalities from core layer and lacking multiresponsiveness for shell layers existing in the dendritic core‐multishell architectures. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis and characterization of folic acid‐modified carboxymethyl chitosan‐ursolic acid targeted nano‐drug carrier for the delivery of ursolic acid and 10‐hydroxycamptothecin

Carboxymethyl chitosan (CMCS), as a water‐soluble, biocompatible, and biodegradable polymer, is an excellent carrier for a sustained drug delivery system. In this study, a amphiphilic carboxymethyl chitosan‐ursolic acid nano‐drug carrier modified by folic acid (FPCU) were prepared, and then the nano‐drug carrier wrapped another anticancer drug 10‐hydroxycamptothecin were self‐assembled into nanoparticles (FPCU/HCPT NPs). The FPCU/HCPT NPs had a suitable size, high drug loading efficiency of ursolic acid (6.4%) and 10‐hydroxycamptothecin (14.1%). The drug release study in vitro indicated that the nanoparticles have obviously sustained effect and pH sensitive behaviors, the drug release amount was higher at pH 5.5 than at pH 7.4. in vitro and in vivo study showed that the nanoparticles displayed a high antitumor efficiency to tumor cells compared with free drug. The nano delivery system as a carrier for ursolic acid (UA) and 10‐hydroxycamptothecin (HCPT) has good application prospects in cancer treatment.     

Hyaluronic Acid/Poly(β‐Amino Ester) Polymer Nanogels for Cancer‐Cell‐Specific NIR Fluorescence Switch

Cancer‐cell‐specific pH‐activatable polymer nanogels consisting of CD44‐receptor‐targeting hyaluronic acid (HA), pH‐sensitive poly(β‐amino ester) (PBAE), and near‐infrared (NIR) fluorescent indocyanine green (ICG) were synthesized and used to detect cancer cells. The HA/PBAE/ICG‐polymer‐nanogel‐based NIR probe was nonfluorescent outside of tumor cells. After internalization by CD44‐receptor‐mediated endocytosis, the probe accumulated in the late endosomes or lysosomes where the acidic pH solubilized the PBAE and caused instant disassembly of the polymer nanogel. During endosomal maturation, the encapsulated ICG was released from its quenched state, inducing strong NIR fluorescence recovery. The nanogels generate a highly tumor‐specific NIR signal with a reduced background signal.     

pH‐responsive squeezing polysaccharidic nanogels for efficient docetaxel delivery

In this study, we report pH‐responsive polysaccharidic nanogels comprising starch grafted with 3‐(diethylamino)propylamine (DEAP, as an inner soft nanogel core) and poly(ethylene glycol) (PEG, as an outer hydrophilic nanogel shell). Here, the DEAP moieties (pK_b ~ pH 7.0) enhance the lipophilicity of the nanogel core at pH 7.4, improving the loading efficiency of an antitumor model drug (docetaxel [DTX]) in the core. However, the DEAP moieties could be protonated below pH 7.0, resulting in the mediation of ion‐dipole interactions with hydroxyl groups abundant in starch backbone. This event causes the electrostatic condensation of the nanogel core and enables the acceleration of drug release by squeezing of the core. We demonstrated that the nanogels selectively release the drug given a weakly acidic pH stimulus. These drug release trends are reversible with changes in pH. As a result, the nanogels are able to efficiently reduce MDA‐MB‐231 tumor cell population in acidic pH environments.     

pH‐ and β‐cyclodextrin‐responsive micelles based on polyaspartamide derivatives as drug carrier

A novel kind of graft polymer poly(aspartic acid)‐ethanediamine‐g‐adamantane/methyloxy polyethylene glycol (Pasp‐EDA‐g‐Ad/mPEG) was designed and synthesized for drug delivery in this study. The chemical structure of the prepared polymer was confirmed by proton NMR. The obtained polymer can self‐assemble into micelles which were stable under a physiological environment and displayed pH‐ and β‐cyclodextrin (β‐CD)‐responsive behaviors because of the acid‐labile benzoic imine linkage and hydrophobic adamantine groups in the side chains of the polymer. The doxorubicin (Dox)‐loaded micelles showed a slow release under physiological conditions and a rapid release after exposure to weakly acidic or β‐CD environment. The in vitro cytotoxicity results suggested that the polymer was good at biocompatibility and could remain Dox biologically active. Hence, the Pasp‐EDA‐g‐Ad/mPEG micelles may be applied as promising controlled drug delivery system for hydrophobic antitumor drugs. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1387–1395     

An Adjustable pH‐Responsive Drug Delivery System Based on Self‐Assembly Polypeptide‐Modified Mesoporous Silica

In this study, an adjustable pH‐responsive drug delivery system using mesoporous silica nanoparticles (MSNs) as the host materials and the modified polypeptides as the nanovalves is reported. Since the polypeptide can self‐assemble via electrostatic interaction at pH 7.4 and be disassembled by pH changes, the modified poly(l ‐lysine) and poly(l ‐glutamate) are utilized for pore blocking and opening in the study. Poly(l ‐lysine)‐MSN (PLL‐MSN) and poly(l ‐glutamate)‐MSN (PLG‐MSN) are synthesized via the ring opening polymerization of N‐carboxyanhydrides onto the surface of mesoporous silica nanoparticles. The successful modification of the polypeptide on MSN is proved by Zeta potential change, X‐ray photoelectron spectroscopy (XPS), solid state NMR, and MALDI‐TOF MS. In vitro simulated dye release studies show that PLL‐MSN and PLG‐MSN can successfully load the dye molecules. The release study shows that the controlled release can be constructed at different pH by adjusting the ratio of PLL‐MSN to PLG‐MSN. Cellular uptake study indicates that the drug is detected in both cytoplasm and nucleus, especially in the nucleus. In vitro cytotoxicity assay indicates that DOX loaded mixture nanoparticles (ratio of PLL‐MSN to PLG‐MSN is 1:1) can be triggered for drug release in HeLa cells, resulting in 88% of cell killing.     

Dendron‐like poly(ε‐benzyloxycarbonyl‐L‐lysine)/linear PEO block copolymers: Synthesis,physical characterization,self‐assembly,and drug‐release behavior

Dendron‐like poly(ε‐benzyloxycarbonyl‐L ‐lysine)/linear poly(ethylene oxide) block copolymers (i.e., Dm‐PZLys‐b‐PEO, m = 0 and 3; Dm are the propargyl focal point poly(amido amine) dendrons having 2^m primary amine groups) were for the first time synthesized by combining ring‐opening polymerization (ROP) of ε‐benzyloxycarbonyl‐L ‐lysine N‐carboxyanhydride (Z‐Lys‐NCA) and click chemistry, where Dm‐PZLys homopolypeptides were click conjugated with azide‐terminated PEO. Their molecular structures and physical properties were characterized in detail by FTIR, ¹H NMR, gel permeation chromatography, differential scanning calorimetry, polarized optical microscopy, and wide angle X‐ray diffraction. Both homopolypeptides and copolymers presented a liquid crystalline phase transition for PZLys block, and the transition was irreversible. Moreover, the degree of crystallinity of PEO block within linear copolymers decreased from 96.2% to 20.4% with increasing PZLys composition, whereas that within dendritic copolymers decreased to zero. The secondary conformation of PZLys progressively changed from β‐sheet to α‐helix with increasing the chain length. These copolymers self‐assembled into spherical nanoparticles in aqueous solution, and the anticancer drug doxorubicin‐loaded nanoparticles gave a similar morphology compared with their blank counterparts. The drug‐loaded nanoparticles showed a triphasic drug‐release profile at aqueous pH 7.4 or 5.5 and 37 °C and sustained a longer drug‐release period for about 2 months. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis,self‐assembly,drug‐release behavior,and cytotoxicity of triblock and pentablock copolymers composed of poly(ε‐caprolactone), poly(L‐lactide), and poly(ethylene glycol)

Biocompatible and biodegradable ABC and ABCBA triblock and pentablock copolymers composed of poly(ε‐caprolactone) (PCL), poly(L ‐lactide) (PLA), and poly(ethylene glycol) (PEO) with controlled molecular weights and low polydispersities were synthesized by a click conjugation between alkyne‐terminated PCL‐b‐PLA and azide‐terminated PEO. Their molecular structures, physicochemical and self‐assembly properties were thoroughly characterized by means of FT‐IR, ¹H‐NMR, gel permeation chromatography, differential scanning calorimetry, wide‐angle X‐ray diffraction, dynamic light scattering, and transmission electron microscopy. These copolymers formed microphase‐separated crystalline materials in solid state, where the crystallization of PCL block was greatly restricted by both PEO and PLA blocks. These copolymers self‐assembled into starlike and flowerlike micelles with a spherical morphology, and the micelles were stable over 27 days in aqueous solution at 37 °C. The doxorubicin (DOX) drug‐loaded nanoparticles showed a bigger size with a similar spherical morphology compared to blank nanoparticles, demonstrating a biphasic drug‐release profile in buffer solution and at 37 °C. Moreover, the DOX‐loaded nanoparticles fabricated from the pentablock copolymer sustained a longer drug‐release period (25 days) at pH 7.4 than those of the triblock copolymer. The blank nanoparticles showed good cell viability, whereas the DOX‐loaded nanoparticles killed fewer cells than free DOX, suggesting a controlled drug‐release effect. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

羟丙基-β-环糊精磁性复合微粒的合成及作为阿霉素载体的体外释药研究

羟丙基-β-环糊精因具有内部疏水和外部亲水锥形圆筒空腔结构和良好的生物相容性在磁性药物载体方面有潜在应用价值。本研究将羟丙基-β-环糊精修饰在超顺磁性纳米四氧化三铁粒子表面制备磁性复合微粒,用红外光谱,透射电镜,振动磁强计,电感耦合等离子发射等方法对该复合微粒进行了表征,并将其用于抗肿瘤药物阿霉素的体外载药与释药实验研究。结果表明该复合微粒的粒径大小在10-20nm,饱和磁化强度59.9 emu/g,铁含量55.4%。对阿霉素的载药量为87.8 μg/mg。体外释药结果显示载药复合粒子在PBS中1天,4天,10天的累积释药量分别为35.5%, 49.3%, 76.5%,表明该载体具有一定的药物缓释功能。由此可知,羟丙基-β-环糊精磁性复合微粒可作为磁性靶向给药系统的有效载体。     

Preparation of β‐cyclodextrin‐gold nanoparticles modified open tubular column for capillary electrochromatographic separation of chiral drugs

In this paper, β‐cyclodextrin (β‐CD) modified gold nanoparticles (AuNPs) coated open tubular column (OT column) was prepared for capillary electrochromatography. The open tubular column was constructed through self‐assembly of gold nanoparticles on 3‐mercaptopropyl‐trimethoxysilane (MPTMS) prederivatized capillary and subsequent modification of thiols β‐cyclodextrin (SH‐β‐CD). Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and ultraviolet visible spectroscopy were carried out to characterize the prepared open tubular column and synthesized gold nanoparticles. By comparing different coating times of gold nanoparticles and thiols β‐cyclodextrin, we got the optimal conditions for preparing the open tubular column. Also, the separation parameters were optimized including buffer pH, buffer concentration and applied voltage. Separation effectiveness of open tubular column was verified by the separation of four pairs of drug enantiomers including bifonazole, fexofenadine, omeprazole and lansoprazole, and satisfactory separation results were achieved for these analytes studied. In addition, the column showed good stability and repeatability. The relative standard deviation values less than 5% were obtained through intra‐day, inter‐day, and column‐to‐column investigations.     

β‐cyclodextrin‐based polymeric nano‐receptor: the self‐assembly of cyclodextrin‐appended comb‐copolymer

Well‐defined β‐cyclodextrin (β‐CD)‐appended biocompatible comb‐copolymer ethyl cellulose‐graft‐poly (ε‐caprolactone) (EC‐g‐PCL) was synthesized via the combination of ring‐opening polymerization (ROP) and click chemistry. The resulting products were characterized by ¹H NMR, FT‐IR spectroscopy, and GPC. The synthesized comb‐copolymer could assemble to micelles, with the surface covered by β‐CD. The inclusion with ferrocene derivation was investigated by cyclic voltammetric (CV) experiments, which indicated the potential application of the micelles as nano‐receptors for molecule recognization and controlled drug release. Copyright © 2011 John Wiley & Sons, Ltd.     

Poly(4‐acryloylmorpholine) oligomers carrying a β‐cyclodextrin residue at one terminus

A straightforward synthesis of amphiphilic β‐cyclodextrin‐poly(4‐acryloylmorpholine) (β‐CD‐PACM) polymers of controlled molecular weight, consisting of the radical polymerization of 4‐acryloylmorpholine in the presence of 6‐deoxy‐6‐mercapto‐β‐cyclodextrin (β‐CD‐SH) as chain‐transfer agent, has been established. These derivatives carry a single β‐cyclodextrin (β‐CD) moiety at one terminus and their average molecular weight is in the order of 10⁴. Thus, their β‐CD content is ～ 10% by weight. No evidence of un‐functionalized PACM was found in the final products. The chain‐transfer constant (C_T) of β‐CD‐SH was found to be 1.30 by independently determining the reaction constants of both chain‐transfer and propagation reactions. This ensures that the molecular weight, hence the β‐CD content of the polymers, does not significantly vary with conversion. These β‐CD‐PACM polymers are highly soluble in water as well as in several organic solvents such as chloroform and lower alcohols. They proved capable of solubilizing in water poorly soluble drugs such as 9‐[(2‐hydroxyethoxy)methyl]guanine (Acyclovir) and of gradually releasing them in aqueous systems. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1607–1617, 2008     

Meticulous Doxorubicin Release from pH-Responsive Nanoparticles Entrapped within an Injectable Thermoresponsive Depot

The dual stimuli-controlled release of doxorubicin from gel-embedded nanoparticles is reported. Non-cytotoxic polymer nanoparticles are formed from poly(ethylene glycol)-b-poly(benzyl glutamate) that, uniquely, contain a central ester link. This connection renders the nanoparticles pH-responsive, enabling extensive doxorubicin release in acidic solutions (pH 6.5), but not in solutions of physiological pH (pH 7.4). Doxorubicin-loaded nanoparticles were found to be stable for at least 31 days and lethal against the three breast cancer cell lines tested. Furthermore, doxorubicin-loaded nanoparticles could be incorporated within a thermoresponsive poly(2-hydroxypropyl methacrylate) gel depot, which forms immediately upon injection of poly(2-hydroxypropyl methacrylate) in dimethyl sulfoxide solution into aqueous solution. The combination of the poly(2-hydroxypropyl methacrylate) gel and poly(ethylene glycol)-b-poly(benzyl glutamate) nanoparticles yields an injectable doxorubicin delivery system that facilities near-complete drug release when maintained at elevated temperatures (37 °C) in acidic solution (pH 6.5). In contrast, negligible payload release occurs when the material is stored at room temperature in non-acidic solution (pH 7.4). The system has great potential as a vehicle for the prolonged, site-specific release of chemotherapeutics.     

Synthesis and Characterization of pH‐Sensitive Positive‐charge Silica Nanoparticles for Oral Anionic Drug Delivery

The objective of this study is to utilize the pH sensitivity of modified mesoporous silica nanoparticles (MSN) for oral drug delivery. In the first time, a pH‐sensitive ionic liquid was synthesized through the quaternization of 3‐aminopropyltrimethoxysilane (3‐ATMS) with sodium monochloroacetate (SMCA). Then, silica nanoparticle was modified by this pH‐sensitive ionic liquid and converted to a pH‐sensitive positive‐charge silica nanoparticle (PCSN). The nanoparticle was characterized by FTIR and SEM. Naproxen as anionic drug molecules was entrapped in this pH‐sensitive positive‐charge silica nanoparticles (PCSN) and the in vitro release profiles were established separately in both (SGF, pH 1) and (SIF, pH 7.4).     

Design and proof of reversible micelle‐to‐vesicle multistimuli‐responsive morphological regulations

Multistimuli‐responsive precise morphological control over self‐assembled polymers is of great importance for applications in nanoscience as drug delivery system. A novel pH, photoresponsive, and cyclodextrin‐responsive block copolymer were developed to investigate the reversible morphological transition from micelles to vesicles. The azobenzene‐containing block copolymer poly(ethylene oxide)‐b‐poly(2‐(diethylamino)ethyl methacrylate‐co‐6‐(4‐phenylazo phenoxy)hexyl methacrylate) [PEO‐b‐P(DEAEMA‐co‐PPHMA)] was synthesized by atom transfer radical polymerization. This system can self‐assemble into vesicles in aqueous solution at pH 8. On adjusting the solution pH to 3, there was a transition from vesicles to micelles. The same behavior, that is, transition from vesicles to micelles was also realizable on addition of β‐cyclodextrin (β‐CD) to the PEO‐b‐P(DEAEMA‐co‐PPHMA) solution at pH 8. Furthermore, after β‐CD was added, alternating irradiation of the solution with UV and visible light can also induce the reversible micelle‐to‐vesicle transition because of the photoinduced trans‐to‐cis isomerization of azobenzene units. The multistimuli‐responsive precise morphological changes were studied by laser light scattering, transmission electron microscopy, and UV–vis spectra. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

pH‐responsive polymer core–shell nanospheres for drug delivery

Stimuli‐responsive polymer nanoparticles are playing an increasingly more important role in drug delivery applications. However, limited knowledge has been accumulated about processes which use stimuli‐responsive polymer nanospheres (matrix nanoparticles whose entire mass is solid) to carry and deliver hydrophobic therapeutics in aqueous solution. In this research, pyrene was selected as a model hydrophobic drug and a pyrene‐loaded core‐shell structured nanosphere named poly(DEAEMA)‐poly(PEGMA) was designed as a drug carrier where DEAEMA and PEGMA represent 2‐(diethylamino)ethyl methacrylate and poly(ethylene glycol) methacrylate, respectively. The pyrene‐loaded core‐shell nanospheres were prepared via an in situ two‐step semibatch emulsion polymerization method. The particle size of the core‐shell nanosphere can be well controlled through adjusting the level of surfactant used in the polymerization where an average particle diameter of below 100 nm was readily achieved. The surfactant was removed via a dialysis operation after polymerization. Egg lecithin vesicles (liposome) were prepared to mimic the membrane of a cell and to receive the released pyrene from the nanosphere carriers. The in vitro release profiles of pyrene toward different pH liposome vesicles were recorded as a function of time at 37 °C. It was found that release of pyrene from the core‐shell polymer matrix can be triggered by a change in the environmental pH. In particular the pyrene‐loaded nanospheres are capable of responding to a narrow window of pH change from pH = 5, 6, to 7 and can achieve a significant pyrene release of above 80% within 90 h. The rate of release increased with a decrease in pH. A first‐order kinetic model was proposed to describe the rate of release with respect to the concentration of pyrene in the polymer matrix. The first‐order rate constant of release k was thus determined as 0.049 h^?1 for pH = 5; 0.043 h^?1 for pH = 6; and 0.035 h^?1 for pH = 7 at 37 °C. The release of pyrene was considered to follow a diffusion‐controlled mechanism. The synthesis and encapsulation process developed herein provides a new approach to prepare smart nanoparticles for efficient delivery of hydrophobic drugs. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4440–4450     

pH‐responsive near‐infrared emitting conjugated polymer nanoparticles for cellular imaging and controlled‐drug delivery

In this article, pH‐responsive near‐infrared emitting conjugated polymer nanoparticles (CPNs) are prepared, characterized, and their stabilities are investigated under various conditions. These nanoparticles have capacity to be loaded with water insoluble, anticancer drug, camptothecin (CPT), with around 10% drug loading efficiency. The in vitro release studies demonstrate that the release of CPTs from CPNs is pH‐dependent such that significantly faster drug release at mildly acidic pH of 5.0 compared with physiological pH 7.4 is observed. Time and dose‐dependent in vitro cytotoxicity tests of blank and CPT‐loaded nanoparticles are performed by real‐time cell electronic sensing (RT‐CES) assay with hepatocellular carcinoma cells (Huh7). The results indicate that CPNs can be effectively utilized as vehicles for pH‐triggered release of anticancer drugs. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 114–122     

Gas‐forming poly(ethylene glycol)‐b‐poly(L‐lactic acid) micelles

In this study, a novel drug‐carrying micelle composed of methoxy poly(ethylene glycol) (mPEG)‐b‐poly(L‐lactic acid) (PLLA) with gas‐forming carbonate linkage was fabricated. Here, the gas‐forming carbonate linkage was formed by the chemical coupling of the terminal hydroxyl group of the PLLA block and benzyl chloroformate (BC). mPEG‐b‐PLLA‐BC was self‐organized in aqueous solution: the PEG block on the hydrophilic outer shell and the PLLA‐BC block in the hydrophoboic innor core. The cleavage of carbonate linkage by hydrolysis and formation of carbon dioxide nanobubbles in the micellar core enabled an accelerated release of the encapsulated anticancer drug (doxorubicin: DOX) from the mPEG‐b‐PLLA‐BC micelles. The amount of drug (DOX) released from the mPEG‐b‐PLLA‐BC micelle was higher than that from the conventional mPEG‐b‐PLLA micelle, which allowed for increased in vitro toxicity against KB tumor cells. Copyright © 2013 John Wiley & Sons, Ltd.