Polymerization-Induced Self-Assembly (PISA) – control over the morphology of nanoparticles for drug delivery applications

Karagöz, Bünyamin; Esser, Lars; Duong, Hien T. T.; Basuki, Johan Sebastian; Boyer, Cyrille; Davis, Thomas P.

doi:10.1039/c3py01306e

Cited by 297 publications

(305 citation statements)

References 71 publications

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“…5,6 Subsequently, we engineered the pH-responsive polymersomes as a smart drug delivery vehicle and the intracellular pH gradient was employed as the triggering event to regulate the release of encapsulants. 73,74 As expected, both hydrophilic anticancer drug, DOX·HCl, and hydrophobic model drug, Nile red, could be embedded into the aqueous lumen and the hydrophobic bilayer of the polymersomes, respectively. The pH-induced release of loaded DOX·HCl and Nile red was monitored by the evolution of the corresponding fluorescence intensities recorded at 598 and 625 nm for DOX and Nile red, respectively (Figure 4, Figures S7 and S8).…”

Section: Macromoleculesmentioning

confidence: 80%

Acid-Disintegratable Polymersomes of pH-Responsive Amphiphilic Diblock Copolymers for Intracellular Drug Delivery

et al. 2015

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Supramolecular vesicles, also referred to as polymersomes, self-assembled from amphiphilic polymers capable of synchronically loading with both hydrophilic and hydrophobic payloads have shown promising potential in drug delivery application. Herein, we report the fabrication of pH-responsive polymersomes via supramolecular self-assembly of amphiphilic diblock copolymers, poly(ethylene oxide)-b-poly(2-((((5-methyl-2-(2,4,6-trimethoxyphenyl)-1,3-dioxan-5-yl)methoxy)carbonyl)amino)ethyl methacrylate) (PEO-b-PTTAMA), which were synthesized via reversible addition−fragmentation chain transfer (RAFT) polymerization of a pHresponsive monomer (i.e., TTAMA) using a PEO-based macroRAFT agent. The resultant amphiphilic diblock copolymer then self-assembled into vesicles consisting of hydrophilic PEO coronas and pH-responsive hydrophobic bilayers, as confirmed by TEM and DLS measurements. The polymersomes containing cyclic benzylidene acetals in the hydrophobic bilayers were relatively stable under neutral pH, whereas they underwent hydrolysis with the liberation of hydrophobic 2,4,6-trimethoxybenzaldehyde and the simultaneous generation of hydrophilic diol moieties upon exposure to acidic pH milieu, which could be monitored by UV/vis spectroscopy, SEM, and TEM observations. By loading hydrophobic model drug (Nile red) as well as hydrophilic chemotherapeutic drug (doxorubicin hydrochloride, DOX·HCl) into the bilayer and aqueous interior of the polymersomes, the subsequent release of Nile red and DOX·HCl payloads was remarkably regulated by the solution pH values, and a lower pH value led to a faster drug release profile. In vitro experiment, observed by a confocal laser scanning microscope (CLSM), revealed that the pH-responsive polymersomes were easily taken up by HeLa cells and were primarily located in the acidic organelles after internalization, where the pH-responsive cyclic acetal moieties were hydrolyzed and the embedded payloads were therefore released, allowing for on-demand release of the encapsulants mediated by intracellular pH. In addition to small molecule chemotherapeutic drugs, biomacromolecules (alkaline phosphatase, ALP) can also be encapsulated into the aqueous lumen of the polymersomes. Significantly, the pH-triggered degradation of polymersomes could also regulate the release of encapsulated ALP, as confirmed by ALP-activated fluorogenic reaction. ■ INTRODUCTIONSupramolecular vesicles, also known as polymersomes, are commonly made from the self-assembly of amphiphilic block copolymers, in the core of which is an aqueous compartment enclosed by a hydrophobic bilayer membrane. Integrating both hydrophilic and hydrophobic characteristics, polymersomes are distinguished by good colloidal stability, high mechanical strength, and long circulation time compared to liposome counterparts. 1−3 These unique advantages make them quite promising for drug delivery application, in which both hydrophobic and hydrophilic drugs can be simultaneously embedded. 4−9 Nevertheless, although the impermeable nature of bilayers c...

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Section: Macromoleculesmentioning

confidence: 80%

Acid-Disintegratable Polymersomes of pH-Responsive Amphiphilic Diblock Copolymers for Intracellular Drug Delivery

et al. 2015

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“…Related (co)polymers have been further employed to engineer polymer materials for specific applications: injectable hydrogels [23][24][25][26], microgels via a microfluidic device [27], or shell crosslinked micelles [28] obtained with dihydrazide cross-linkers. Nanoparticles were also formed using a copolymer based on vinylbenzaldehyde units; further cross-linking or conjugation with chemotherapy compounds via Schiff base or imine formation was achieved [29]. Lastly, poly(4-vinyl benzaldehyde) has also been successfully functionalized with desired compounds using the Kabachnik-Fields post-polymerization reaction [30].…”

Section: Introductionmentioning

confidence: 99%

Aldehyde-functional copolymers based on poly(2-oxazoline) for post-polymerization modification

Legros

Pauw‐Gillet

Tam

et al. 2015

European Polymer Journal

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“…[ 28 ] Similar to post-polymerization block copolymer assemblies, those prepared through PISA could also fi nd use as organic templates for the deposition of inorganic materials. Using functional core-shell spheres or vesicles, composite structures comprising silica [ 11 ] particles or metallic substructures (iron oxide, [ 71 , 85a ] silver [ 76a ] or gold particles [ 72b ] have already been designed.…”

mentioning

confidence: 99%

Guidelines for the Synthesis of Block Copolymer Particles of Various Morphologies by RAFT Dispersion Polymerization

Rieger

2015

Macromol. Rapid Commun.

311

326

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This article presents the recent developments of radical dispersion polymerizaton controlled by reversible addition fragmentation chain transfer (RAFT) for the production of block copolymer particles of various morphologies, such as core-shell spheres, worms, or vesicles. It is not meant to be an exhaustive review but it rather provides guidelines for non-specialists. The article is subdivided into eight sections. After a general introduction, the mechanism of polymerization-induced self-assembly (PISA) through RAFT-mediated dispersion polymerization is presented and the different parameters that control the morphology produced are discussed. The next two sections are devoted to the choice of the monomer/solvent pair and the macroRAFT agent. Afterwards, post-polymerization morphological order-to-order transitions (i.e. morphological transitions triggered by extrinsic stimuli) or order-to-disorder transitions (i.e. disassembly of chains) are discussed. Assemblies based on more complex polymer architectures, such as triblock copolymers, are presented next, and finally the possibility to stabilize these structures by crosslinking is reported. The manuscript ends with a short conclusion and an outlook.

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Polymerization-Induced Self-Assembly (PISA) – control over the morphology of nanoparticles for drug delivery applications

Cited by 297 publications

References 71 publications

Acid-Disintegratable Polymersomes of pH-Responsive Amphiphilic Diblock Copolymers for Intracellular Drug Delivery

Acid-Disintegratable Polymersomes of pH-Responsive Amphiphilic Diblock Copolymers for Intracellular Drug Delivery

Aldehyde-functional copolymers based on poly(2-oxazoline) for post-polymerization modification

Guidelines for the Synthesis of Block Copolymer Particles of Various Morphologies by RAFT Dispersion Polymerization

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