Thermally induced micelle to vesicle morphology transition for a charged chain end diblock copolymer

Moughton, Adam O.; O’Reilly, Rachel K.

doi:10.1039/b922289h

Cited by 160 publications

(150 citation statements)

References 30 publications

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“…The air dried samples in Figures 4A and 4B show only minor shrinkage/core collapse of the vesicle structures after air drying, and still maintain vesicle wall integrity, with sizes (~250 nm) slightly lower than those obtained in DLS where the vesicles are in a hydrated state; a commonly reported observation. 73,74 This vacuum dried sample was analysed without staining so that any dense platinum regions could be visualised. The dense (darker) holes in the structures,…”

Section: Cddp Loading Of Block Copolymer/vesicle Formationmentioning

confidence: 99%

Cisplatin-Induced Formation of Biocompatible and Biodegradable Polypeptide-Based Vesicles for Targeted Anticancer Drug Delivery

Shirbin

Ladewig

et al. 2015

Biomacromolecules

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Novel cisplatin (CDDP)-loaded, polypeptide-based vesicles for the targeted delivery of cisplatin to cancer cells have been prepared. These vesicles were formed from biocompatible and biodegradable maleimide-poly(ethylene oxide)114-b-poly(L-glutamic acid)12 (Mal-PEG114-b-PLG12) block copolymers upon conjugation with the drug itself. CDDP conjugation forms a short, rigid, cross-linked, drug-loaded, hydrophobic block in the copolymer, and subsequently induces self-assembly into hollow vesicle structures with average hydrodynamic diameters (Dh) of ∼ 270 nm. CDDP conjugation is critical to the formation of the vesicles. The reactive maleimide-PEG moieties that form the corona and inner layer of the vesicles were protected via formation of a reversible Diels-Alder (DA) adduct throughout the block copolymer synthesis so as to maintain their integrity. Drug release studies demonstrated a low and sustained drug release profile in systemic conditions (pH = 7.4, [Cl(-)] = 140 mM) with a higher "burst-like" release rate being observed under late endosomal/lysosomal conditions (pH = 5.2, [Cl(-)] = 35 mM). Further, the peripheral maleimide functionalities on the vesicle corona were conjugated to thiol-functionalized folic acid (FA) (via in situ reduction of a novel bis-FA disulfide, FA-SS-FA) to form an active targeting drug delivery system. These targeting vesicles exhibited significantly higher cellular binding/uptake into and dose-dependent cytotoxicity toward cancer cells (HeLa) compared to noncancerous cells (NIH-3T3), which show high and low folic acid receptor (FR) expression, respectively. This work thus demonstrates a novel approach to polypeptide-based vesicle assembly and a promising strategy for targeted, effective CDDP anticancer drug delivery.

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Section: Cddp Loading Of Block Copolymer/vesicle Formationmentioning

confidence: 99%

Cisplatin-Induced Formation of Biocompatible and Biodegradable Polypeptide-Based Vesicles for Targeted Anticancer Drug Delivery

Shirbin

Ladewig

et al. 2015

Biomacromolecules

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“…Raft agent 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT) was synthesised based on previous work. 34 …”

Section: Methodsmentioning

confidence: 99%

Understanding the CDSA of poly(lactide) containing triblock copolymers

et al. 2017

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Crystallisation-driven self-assembly (CDSA) has become an extremely valuable technique in the preparation of well-defined nanostructures using diblock copolymers. The use of triblock copolymers is considerably less well-known on account of more complex syntheses and assembly methods despite the functional advantages provided by a third block. Herein, we show the simple preparation of well-defined tuneable 1D and 2D structures based on poly(lactide) triblock copolymers of different block ratios synthesised by ring-opening polymerisation (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerisation, where a phase diagram based on a novel unimer solubility approach is proposed. Using a series of poly(L-lactide)-b-poly(N,N-dimethylacrylamide) (PLLA-b-PDMA) diblock copolymers and PDMA-b-PLLA-b-PDMA triblock copolymers with different core/corona ratios, single solvent CDSA processes revealed that comparatively hydrophilic polymers were liable to achieve 2D platelets, while the less hydrophilic counterparts yield 'transition state' wide cylinders and pure 1D cylinders. The length of crystalline core block is also shown to play an important role in fixed corona/core ratio systems, where a longer core block is prone to form cylindrical structures due to a lack of overall solubility, whereas a shorter block forms platelets. Importantly, this approach reveals contrary results to conventional theories, which state that longer solvophilic blocks relative to the core-forming block should favour more curved core/corona interfaces. Our morphological transitions are shown in both di-and tri-block copolymer systems, showing the generalisation of these assembly methods towards promising methodologies for the rational design of PLLA-based nanocarriers in the biomedical realm.

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“…[3d] O’Reilly and Moughton used a quaternary amine-functionalized RAFT chain transfer agent (CTA) to prepare a PNIPAM-based diblock copolymer, which self-assembled to form spheres at room temperature. [3e] However, heating above the LCST of the PNIPAM stabilizer altered the packing parameter and induced a morphological sphere-to-vesicle transition: the cationic charge conferred by the CTA-derived end-group located on the PNIPAM chains ensured colloidal stability, rather than macroscopic precipitation. Weaver et al.…”

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confidence: 99%

pH‐Responsive Non‐Ionic Diblock Copolymers: Ionization of Carboxylic Acid End‐Groups Induces an Order–Order Morphological Transition

et al. 2014

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A carboxylic acid based reversible additionfragmentation transfer (RAFT) agent is used to prepare gels composed of worm-like diblock copolymers using two non-ionic monomers, glycerol monomethacrylate (GMA) and 2-hydroxypropyl methacrylate (HPMA). Ionization of the carboxylic acid end-group on the PGMA stabilizer block induces a worm-to-sphere transition, which in turn causes immediate degelation. This morphological transition is fully reversible as determined by TEM and rheology studies and occurs because of a subtle change in the packing parameter for the copolymer chains. A control experiment where the methyl ester derivative of the RAFT agent is used to prepare the same diblock copolymer confirms that no pH-responsive behavior occurs in this case. This end-group ionization approach is important for the design of new pH-responsive copolymer nano-objects as, unlike polyacids or polybases, only a minimal amount of added base (or acid) is required to drive the morphological transition.

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Thermally induced micelle to vesicle morphology transition for a charged chain end diblock copolymer

Abstract: A quaternary amine end functionalised diblock copolymer (PtBuA-b-PNIPAM) has been synthesised using RAFT polymerisation and shown to undergo a thermally induced morphology transition from micelles to vesicles, as evidenced by TEM, AFM, SLS and DLS analyses.

Cited by 160 publications

References 30 publications

Cisplatin-Induced Formation of Biocompatible and Biodegradable Polypeptide-Based Vesicles for Targeted Anticancer Drug Delivery

Cisplatin-Induced Formation of Biocompatible and Biodegradable Polypeptide-Based Vesicles for Targeted Anticancer Drug Delivery

Understanding the CDSA of poly(lactide) containing triblock copolymers

pH‐Responsive Non‐Ionic Diblock Copolymers: Ionization of Carboxylic Acid End‐Groups Induces an Order–Order Morphological Transition

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