Bioreducible unimolecular micelles based on amphiphilic multiarm hyperbranched copolymers for triggered drug release

Pang, Yan; Liu, Jin-yao; Su, Yue; Zhu, Bangshang; Huang, Wei; Zhou, Yongfeng; Zhu, Xinyuan; Yan, Deyue

doi:10.1007/s11426-010-4163-0

Cited by 31 publications

(23 citation statements)

References 57 publications

(61 reference statements)

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“…While crosslinking the nanocarriers is a very effective approach to ensure excellent in vivo stability, it can also lead to a reduced biodegradability and a slower drug release rate, which may not be desirable for in vivo drug/agent delivery applications. Unimolecular micelles, formed by single multi-arm star amphiphilic block copolymers having a sufficient number of arms and proper hydrophobic to hydrophilic ratios, can provide excellent in vivo stability due to their covalent nature without compromising the biodegradability or drug release profile [22,25–28]. Various types of nanostructures including dendrimers, hyperbranched polymers, and functionalized inorganic nanoparticles can be used as the inner core and/or macroinitiators for the conjugation/synthesis of the amphiphilic block copolymer arms [26–29].…”

Section: Introductionmentioning

confidence: 99%

“…Various types of nanostructures including dendrimers, hyperbranched polymers, and functionalized inorganic nanoparticles can be used as the inner core and/or macroinitiators for the conjugation/synthesis of the amphiphilic block copolymer arms [26–29]. Boltorn H40 (H40), a hyperbranched aliphatic polyester, has received much attention in the design of unimolecular micelles because of its biodegradability, biocompatibility, globular architecture, and a large number of terminal functional groups [22,26–28]. …”

Section: Introductionmentioning

confidence: 99%

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Multifunctional unimolecular micelles for cancer-targeted drug delivery and positron emission tomography imaging

et al. 2012

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A multifunctional unimolecular micelle made of a hyperbranched amphiphilic block copolymer was designed, synthesized, and characterized for cancer-targeted drug delivery and non-invasive positron emission tomography (PET) imaging in tumor-bearing mice. The hyperbranched amphiphilic block copolymer, Boltorn® H40-poly(L-glutamate-hydrazone-doxorubicin)-b-poly(ethylene glycol) (i.e., H40-P(LG-Hyd-DOX)-b-PEG), was conjugated with cyclo(Arg-Gly-Asp-D-Phe-Cys) peptides (cRGD, for integrin αvβ3 targeting) and macrocyclic chelators (1,4,7-triazacyclononane-N, N′, N″-triacetic acid [NOTA], for 64Cu-labeling and PET imaging) (i.e., H40-P(LG-Hyd-DOX)-b-PEG-OCH3/cRGD/NOTA, also referred to as H40-DOX-cRGD). The anti-cancer drug, doxorubicin (DOX) was covalently conjugated onto the hydrophobic segments of the amphiphilic block copolymer arms (i.e., PLG) via a pH-labile hydrazone linkage to enable pH-controlled drug release. The unimolecular micelles exhibited a uniform size distribution and pH-sensitive drug release behavior. cRGD-conjugated unimolecular micelles (i.e., H40-DOX-cRGD) exhibited a much higher cellular uptake in U87MG human glioblastoma cells due to integrin αvβ3-mediated endocytosis than non-targeted unimolecular micelles (i.e., H40-DOX), thereby leading to a significantly higher cytotoxicity. In U87MG tumor-bearing mice, H40-DOX-cRGD-64Cu also exhibited a much higher level of tumor accumulation than H40-DOX-64Cu, measured by non-invasive PET imaging and confirmed by biodistribution studies and ex vivo fluorescence imaging. We believe that unimolecular micelles formed by hyperbranched amphiphilic block copolymers that synergistically integrate passive and active tumor-targeting abilities with pH-controlled drug release and PET imaging capabilities provide the basis for future cancer theranostics.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multifunctional unimolecular micelles for cancer-targeted drug delivery and positron emission tomography imaging

et al. 2012

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“…In contrast to linear doubly hydrophilic copolymers, doubly hydrophilic star copolymers with a dendritic core and many linear arms can easily form unimolecular micelles 19–24. Correspondingly, the hydrophobic drugs can be readily encapsulated into the interior cavities of these unimolecular micelles.…”

Section: Introductionmentioning

confidence: 99%

Doubly Hydrophilic Multiarm Hyperbranched Polymers with Acylhydrazone Linkages as Acid‐Sensitive Drug Carriers

Wang

Zhu

et al. 2011

Macromolecular Bioscience

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A novel type of drug carrier capable of controlled drug release is proposed. It consists of an acid-sensitive doubly hydrophilic multiarm hyperbranched copolymer with a hyperbranched polyamidoamine core and many linear poly(ethylene glycol) arms. Using pH-sensitive acylhydrazone linkages, the polymer forms unimolecular micelles that can encapsulate hydrophobic drugs. Due to their amphiphilicity, the drug-loaded unimolecular micelles can self-assemble into multimolecular micelles that show acid-triggered intracellular delivery of the hydrophobic drugs.

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“…For the drug release system, a great number of materials can be utilized such as supermolecule, block copolymers, hyperbranched polymers, etc. Yan et al synthesized a series of hyperbranched copolymers and explored their applications, especially in drug release [4,11,12].In their researches, two kinds of novel temperature-responsive hyperbranched multiarm copolymers were successfully synthesized via the atom transfer radical polymerization (ATRP). Poly(3-ethyl-3-(hydroxymethyl) oxetane) (HBPO) core and thermosensitive poly(N-isopropylacrylamide) (PNIPAM) arms were synthesized from NIPAM monomers by using a hyperbranched HBPO macroinitiator.…”

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Focus on polymer chemistry papers in Science China Chemistry of the year 2010

2011

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The journal Science China Chemistry published 63 papers in polymer fields in 2010, leading to a percentage increase of 473% compared to the year 2008 and 70% to the year 2009, respectively (Figure 1). In this year, three polymer Special Topics were designed and published: Biomedical Polymer (Number 3) [1], Advances in Principles of Polymerization (Number 8) [2] and Highly Branched Polymers-Promising Architectural Macromolecules (Number 12) [3]. Several high qualified papers were published and great achievements have been obtained in the year 2010.The Special Topic of Biomedical Polymers was organized by Prof. GAO ChangYou and GU ZhongWei. According to these papers one knows that the applications of biomedical polymers are focusing on drug release [4-8] and gene delivery [9,10]. For the drug release system, a great number of materials can be utilized such as supermolecule, block copolymers, hyperbranched polymers, etc. Yan et al. synthesized a series of hyperbranched copolymers and explored their applications, especially in drug release [4,11,12].In their researches, two kinds of novel temperature-responsive hyperbranched multiarm copolymers were successfully synthesized via the atom transfer radical polymerization (ATRP). Poly(3-ethyl-3-(hydroxymethyl) oxetane) (HBPO) core and thermosensitive poly(N-isopropylacrylamide) (PNIPAM) arms were synthesized from NIPAM monomers by using a hyperbranched HBPO macroinitiator. Moreover, poly(L-lactide) (PLA) inner-shell and poly(ethylene glycol) (PEG) outer-shell with disulfide-linkages between the hydrophobic and hydrophilic moieties was developed as unimolecular micelles. The HBPO-star-PNIPAM self-assembled micelles showed much improved drug encapsulation efficiencies and temperature-dependent sustainable release behavior due to the special micellar structure. The micelles exhibited no apparent cytotoxicity against human HeLa cells. The H40-star-PLA-SS-PEG bioreducible unimolecular micelles were proved as promising carriers for the triggered intracellular delivery of hydrophobic anticancer drugs. Gu's review discussed peptide dendrimers synthesis and functionalization and their applications in biomedicine for drug release and gene delivery [13]. There are two main advantages of the peptide dendrimers, i.e. the size controllable synthesis even to nanometers and the good biocompatibility due to their similar properties as proteins. Therefore, the peptide dendrimers have received considerable attention in biomedicine. They also investigated a novel supramolecular nanoparticle, and studied the drug release behavior and the anti-tumor effects. The results demonstrate that the supramolecular nanoparticles are biocompatible and are promising carriers for drug delivery. Zhang et al. discussed several kinds of stimulus-responsive nanoparticles, including pH-responsive, temperature-responsive, lightresponsive, magnetic-responsive, ultrasound-responsive, pH/

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Bioreducible unimolecular micelles based on amphiphilic multiarm hyperbranched copolymers for triggered drug release

Cited by 31 publications

References 57 publications

Multifunctional unimolecular micelles for cancer-targeted drug delivery and positron emission tomography imaging

Multifunctional unimolecular micelles for cancer-targeted drug delivery and positron emission tomography imaging

Doubly Hydrophilic Multiarm Hyperbranched Polymers with Acylhydrazone Linkages as Acid‐Sensitive Drug Carriers

Focus on polymer chemistry papers in Science China Chemistry of the year 2010

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