Shell cross-linked polymer micelles: stabilized assemblies with great versatility and potential

Thurmond, Kyle; Huang, Haiyong; Clark, Christopher G.; Kowalewski, Tomasz; Wooley, Karen L.

doi:10.1016/s0927-7765(99)00060-0

Cited by 77 publications

(46 citation statements)

References 32 publications

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“…Once reconstituted with water, this graft copolymer (“denatured” state in organic solvents, designated “ S d ”) folded into a uniform nanocarrier (“native” state, designated “ S n ”), in which the side chains were assembled into a hydrophobic core wrapped around by the main PEG chain as a shell. Unlike the traditional micelles assembled by a linear unit, this nanocarrier was folded from a grafted unit, making the final structure more compact and stable [33]. In addition, the hydrophobic core also provided accommodation for co-encapsulating other hydrophobic anticancer drugs through physical interactions such as π-π stacking [9, 34–35].…”

Section: Introductionmentioning

confidence: 99%

Folding graft copolymer with pendant drug segments for co-delivery of anticancer drugs

Tai

Lü

et al. 2014

Biomaterials

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A graft copolymer with pendant drug segment can fold into nanostructures in a protein folding-like manner. The graft copolymer is constructed by directly polymerizing γ-camptothecin-glutamate N-carboxyanhydride (Glu(CPT)-NCA) on multiple sites of poly(ethylene glycol) (PEG)-based main chain via the ring open polymerization (ROP). The “purely” conjugated anticancer agent camptothecin (CPT) is hydrophobic and serves as the principal driving force during the folding process. When exposed to water, the obtained copolymer, together with doxorubicin (Dox), another anticancer agent, can fold into monodispersed nanocarriers (with a diameter of around 50 nm) for dual-drug delivery. Equipped with a PEG shell, the nanocarriers displayed good stability and can be internalized by a variety of cancer cell lines via the lipid raft and clathrin-mediated endocytotic pathway without premature leakage, which showed a high synergetic activity of CPT and Dox toward various cancer cells. In vivo study validated that the nanocarriers exhibited strong accumulation in tumor sites and showed a prominent anticancer activity against the lung cancer xenograft mice model compared with free drugs.

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Section: Introductionmentioning

confidence: 99%

Folding graft copolymer with pendant drug segments for co-delivery of anticancer drugs

Tai

Lü

et al. 2014

Biomaterials

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“…[16,17] In the past decade, different types of crosslinked block copolymer micelles have been developed to overcome the instability problem. [15,18,19] For instance, Wooley and co-workers reported various forms of shell-crosslinked micelles. [20][21][22][23][24][25] Armes and co-workers reported core-crosslinked stimuli-sensitive micelles.…”

Section: Introductionmentioning

confidence: 99%

Reduction‐Sensitive Reversibly Crosslinked Biodegradable Micelles for Triggered Release of Doxorubicin

Meng

Cheng

et al. 2009

Macromolecular Bioscience

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Reduction-responsive reversibly crosslinked biodegradable micelles were developed and applied for triggered release of doxorubicin (DOX). An amphiphilic block copolymer of poly(ethylene glycol) (PEG) and poly(epsilon-caprolactone) (PCL) that contains two lipoyl functional groups at their interface (PEG-L(2)-PCL) has been synthesized. (1)H NMR spectroscopy and gel permeation chromatography (GPC) measurements show that the PEG-L(2)-PCL block copolymer had a controlled composition (PEG 5 kDa and PCL 5.4 kDa) and a polydispersity index (PDI) of 1.36. PEG-L(2)-PCL formed micelles with sizes that ranged from 20 to 150 nm in aqueous solutions, wherein a critical micelle concentration (CMC) of 16 mg.L(-1) was determined. The micelles were readily crosslinked by adding 7.6 mol % of dithiothreitol (DTT) relative to the lipoyl groups. Notably, micelles after crosslinking demonstrated a markedly enhanced stability against dilution, physiological salt concentration, and organic solvent. In the presence of 10 x 10(-3) M DTT, however, micelles were subject to rapid de-crosslinking. In vitro release studies showed minimal release of DOX from crosslinked micelles at a concentration of 10 mg L(-1) (C < CMC, analogous to intravenous injection), wherein less than 15% of the DOX was released in 10 h. In contrast, rapid release of DOX was observed for DOX-loaded non-crosslinked micelles under otherwise the same conditions ( approximately 80% release in 0.5 h). In the presence of 10 x 10(-3) M DTT mimicking an intracellular reductive environment, sustained release of DOX from crosslinked micelles was achieved, in which 75% of the DOX was released in 9 h. These novel reduction-sensitive reversibly crosslinked biodegradable micelles are highly promising for targeted intracellular delivery of anticancer drugs.

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“…In a recent series of pioneering papers, Wooley and co-workers reported the synthesis of shell cross-linked 'knedel' (SCK) micelles (4)(5)(6)(7)(8)(9)(10)(11)(12). According to these authors, these novel supramolecular structures appear to be a hybrid between dendrimers, hollow spheres, latex particles, and block copolymer micelles.…”

Section: Introductionmentioning

confidence: 96%

“…In later papers, both esterification and carbodiimide coupling chemistry were exploited for shell cross-linking of the solvated carboxylic acid residues of St-acrylic acid (St-AA) (6) and isopreneacrylic acid (IP-AA) (9) x diblock copolymers. The factors affecting the dimensions and properties of the SCK micelles such as the degree of shell crosslinking, comonomer ratio in the precursor block copolymer, and the degree of quaternization of the 4VP residues were also examined (10). The encapsulation of small hydrophobic molecules by these SCK micelles has also been examined (//).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Shell Cross-Linked Micelles with Hydrophilic Cores

Bütün

Armes

2000

Stimuli-Responsive Water Soluble and Amphiphilic Polymers

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We review our recent progress in the synthesis of novel shell cross-linked knedel (SCK) micelles. The reversible self-assembly of hydrophilic -hydrophilic block copolymers in aqueous media is exploited in order to develop three new classes of SCK micelles. In each case the micelle cores can be tuned to become hydrophilic or hydrophobic depending on the solution pH, electrolyte concentration or temperature. In our initial studies (1), a tertiary amine methacrylate diblock copolymer was used to prepare SCK micelles of 20-40 nm diameter, with shell cross-linking being achieved using a bifunctional quaternizing agent. Secondly, an ampholytic diblock copolymer was used to prepare zwitterionic SCK micelles with two distinct particle morphologies: Type I micelles, which comprise cationic coronas and anionic cores and Type II micelles, which comprise anionic coronas and cationic cores (2). Finally, a novel tailor -made triblock copolymer was synthesized and utilized in SCK micelle syntheses at high solids (> 10 %) (3). This 'proof-of-concept' experiment suggests that commercial applications of these fascinating nanostructures may be a realistic possibility.

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Shell cross-linked polymer micelles: stabilized assemblies with great versatility and potential

Cited by 77 publications

References 32 publications

Folding graft copolymer with pendant drug segments for co-delivery of anticancer drugs

Folding graft copolymer with pendant drug segments for co-delivery of anticancer drugs

Reduction‐Sensitive Reversibly Crosslinked Biodegradable Micelles for Triggered Release of Doxorubicin

Synthesis of Novel Shell Cross-Linked Micelles with Hydrophilic Cores

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