pH-sensitive drug release of star-shaped micelles with OEG brush corona

Zhao, Sijie; Yang, Huiru; Zuo, Cai; Sun, Lu; Ma, Liang; Wei, Hua

doi:10.1039/c6ra21408h

Cited by 20 publications

(35 citation statements)

References 51 publications

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“…The size observed by TEM is smaller than that determined by DLS. Such discrepancy is reasonable given that the latter is the hydrodynamic diameter of micelles in solution, whereas the former reflects the morphology size of micelles in a dry/dehydrated state …”

Section: Resultsmentioning

confidence: 99%

“…The synthetic procedures of H40‐PCL‐ b ‐POEGMA through “grafting from” approach was identical to the preparation of 4‐arm star‐shaped PCL‐POEGMA block copolymer reported in our previous study except using H40 as the starting initiator . The detailed synthesis procedures were included in the supporting information (SI).…”

Section: Methodsmentioning

confidence: 99%

“…Polymeric micelles self‐assembled from amphiphilic block copolymers in an aqueous solution can serve as an excellent nanocarrier in applications such as drug delivery, sensing, and image enhancement . However, the micelles drug delivery systems based on the linear amphiphilic block copolymers is thermodynamically favorable only above the critical micelle concentration (CMC) of the amphiphilic macromolecules . When the concentration drops below the CMC, the micellar structure becomes instable and disassembly takes place, which hampers its practical applications and clinical translations .…”

Section: Introductionmentioning

confidence: 99%

“…This technique typically suffers from the weaknesses as divergent dendrimer syntheses, increasing the probability of side reactions, such as crosslinking. However, through optimization of the reaction condition, a sophisticated “grafting from” approach has been used in our previous study to synthesize star‐shaped amphiphilic block copolymers, which was adopted herein to prepare well‐defined hyperbranched copolymer, H40‐ b ‐PCL‐ b ‐POEGMA by consecutive ring‐opening polymerization (ROP) and atom transfer radical polymerization (ATRP). The core structure as well as the polymer composition of the nonreducible amphiphilic hyperbranched block copolymers was optimized toward better properties and performance for drug delivery applications.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Optimization of bioreducible micelles self‐assembled from amphiphilic hyperbranched block copolymers for drug delivery

Yang

Zhao

Zhang

et al. 2018

J. Polym. Sci. Part A: Polym. Chem.

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Dendritic polymers‐based unimolecular micelles with enhanced stability are attractive carriers. However, the preparation of dendrimers or dendrons with higher generation remains substantially synthetic challenge due to the increased steric hindrance, multistep and tedious preparation, and low yields. The adoption of Boltorn H40, a commercially available dendritic polymer of Boltorn family containing multiple hydroxyl groups with various functionalities as a dendrimer‐based starting core template for the generation of hyperbranched polymers, offers a straightforward solution to address this problem. To develop universal strategies toward H40‐based amphiphilic block copolymers, the “grafting from” and “grafting to” approaches were both applied in this study. The reduction‐insensitive block copolymers, H40‐b‐poly(ɛ‐caprolactone)‐b‐poly(oligo(ethylene glycol) monomethyl ether methacrylate) (H40‐b‐PCL‐b‐POEGMA), were synthesized by “grafting from” including sequential ring‐opening polymerization (ROP) and atom transfer radical polymerization (ATRP). The core structure and the polymer composition of the nonreducible amphiphilic hyperbranched block copolymers were optimized toward better properties and performance for drug delivery applications, and H40‐PCL15‐b‐POEGMA23 was screened as the best polymer construct relative to H20‐PCL15‐b‐POEGMA23 and H40‐PCL15‐b‐POEGMA32 in terms of micelle stability and drug loading capacity. Therefore, the reducible H40‐b‐PCL‐SS‐POEGMA with an identical core and polymer composition to that of H40‐PCL15‐b‐POEGMA23 was further prepared by “grafting to” using click coupling between H40‐PCL‐azide and P(OEGMA)‐alkyne. The delivery efficacy evaluated by an in vitro cytotoxicity study revealed that the resulting DOX‐loaded reducible micelles of H40‐PCL15‐SS‐POEGMA23 produced greater cytotoxicity in cancer cells than in normal cells and macrophages, therefore, are promising carriers for anticancer drug delivery. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 1383–1394

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Optimization of bioreducible micelles self‐assembled from amphiphilic hyperbranched block copolymers for drug delivery

Yang

Zhao

Zhang

et al. 2018

J. Polym. Sci. Part A: Polym. Chem.

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“…Meanwhile, our group has a long‐term interest in the fabrication of branched polymers for drug delivery applications due to their ability to form unimolecular nanoparticles with enhanced stability, which is highly desirable for in vivo applications. A panel of star‐shaped amphiphilic block copolymers with different degrees of branches (DBs) of 3, 4, and 6 were synthesized and further optimized for drug delivery applications in our previous study . Of the investigated three star‐shaped copolymers, the four‐arm one was screened to be the best formulation in terms of its size, stability, drug loading capacity and drug release properties.…”

Section: Introductionmentioning

confidence: 99%

Fabrication of Reduction‐Responsive Star‐Shaped Amphiphilic Block Copolymers with Click Coupling‐Generated Block Junctions toward Enhanced Therapeutic Efficacy

Wang

Zhao

et al. 2018

Macro Chemistry & Physics

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Incorporation of the reducible disulfide links into delivery systems has been repeatedly highlighted to realize, elegantly, the tradeoff between extracellular stability and intracellular high therapeutic efficacy. Of all the reported introducing strategies, esterification, seemingly the most extensively‐adopted one, suffers from relatively low yield, especially for the esterification coupling between two macromolecules, due to the low condensation efficiency. To improve the coupling efficiency, Cu(I)‐catalyzed azide−alkyne cycloaddition (CuAAc) click coupling with high efficiency and high selectivity is used to incorporate disulfide links to the star‐shaped amphiphilic block copolymers in this study. Interestingly, besides such synthetic advantages, the click coupling‐introduced disulfide joints further endow the resulting star‐shaped copolymer‐based nanocarriers with higher therapeutic efficacy than the analogues containing esterification‐generated disulfide links, in terms of better buffering capacity, greater selective drug release in reducing over nonreducing environments, and higher in vitro cytotoxicity. The disclosed effect of introducing strategy of disulfide link on the delivery efficacy of the drug carriers provides new insights into the structure–property relationship of reduction‐sensitive delivery systems, as well as offering new opportunities for the future design and development of intelligent nanocarriers toward enhanced therapeutic efficacy.

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Fabrication of Reduction‐Sensitive Amphiphilic Cyclic Brush Copolymer for Controlled Drug Release

Meng

Zhang

et al. 2018

Macromolecular Bioscience

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The cyclic brush polymers, due to the unique topological structure, have shown in the previous studies higher delivery efficacy than the bottlebrush analogues as carriers for drug and gene transfer. However, to the best of knowledge, the preparation of reduction-sensitive cyclic brush polymers for drug delivery applications remains unexplored. For this purpose, a reduction-sensitive amphiphilic cyclic brush copolymer, poly(2-hydroxyethyl methacrylate-g-poly(ε-caprolactone)-disulfide link-poly(oligoethyleneglycol methacrylate)) (P(HEMA-g-PCL-SS-POEGMA)) with reducible block junctions bridging the hydrophobic PCL middle layer and the hydrophilic POEGMA outer corona is designed and synthesized successfully in this study via a "grafting from" approach using sequential ring-opening polymerization (ROP) and atom transfer free radical polymerization (ATRP) from a cyclic multimacroinitiator PHEMA. The resulting self-assembled unimolecular core-shell-corona (CSC) micelles show sufficient salt stability and efficient destabilization in the intracellular reducing environment for a promoted drug release toward a greater therapeutic efficacy relative to the reduction-insensitive analogues. The overall results demonstrate the reducible cyclic brush copolymers developed herein provides an elegant solution to the tradeoff between extracellular stability and intracellular high therapeutic efficacy toward efficient anticancer drug delivery.

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pH-sensitive drug release of star-shaped micelles with OEG brush corona

Abstract: We presented herein pH-mediated drug release behaviors from a generally recognized “pH-insensitive” star-shaped PCL-POEGMA micelles, which were attributed primarily to the hydrophilic corona of OEG brushes.

Cited by 20 publications

References 51 publications

Optimization of bioreducible micelles self‐assembled from amphiphilic hyperbranched block copolymers for drug delivery

Optimization of bioreducible micelles self‐assembled from amphiphilic hyperbranched block copolymers for drug delivery

Fabrication of Reduction‐Responsive Star‐Shaped Amphiphilic Block Copolymers with Click Coupling‐Generated Block Junctions toward Enhanced Therapeutic Efficacy

Fabrication of Reduction‐Sensitive Amphiphilic Cyclic Brush Copolymer for Controlled Drug Release

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