Polymeric micelles are representative self-assembly structures of block copolymers and have widely been investigated from both fundamental and applied aspects. In 1995, we discovered polyion complex (PIC) micelles formed from a pair of oppositely charged block copolymers with poly(ethylene glycol) segments through electrostatic interactions in aqueous media, which expanded the concept of polymeric micelle formation in selective solvents. Hereafter, extensive studies have been carried out on PIC micelles, for example, fundamental characterizations as a novel class of self-assembly systems and applications as nanocarrier systems for the delivery of charged molecules with therapeutic efficacies, including nucleic acids and proteins. This review mainly focuses on physicochemical studies on the formation of PIC micelles, particularly the critical molecular factors that have a role to determine the self-assembly scheme of charged block copolymers for micelle structures.
Subscribe to Journal
Get full journal access for 1 year
only $21.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Verduzco, R, Li, X, Pesek, SL & Stein, GE Structure, function, self-assembly, and applications of bottlebrush copolymers. Chem. Soc. Rev. 44, 2405–2420 (2015).
Tritschler, U, Pearce, S, Gwyther, J, Whittell, GR & Manners, I 50th Anniversary Perspective: Functional Nanoparticles from the Solution Self-Assembly of Block Copolymers. Macromolecules 50, 3439–3463 (2017).
Cabral, H & Kataoka, K Progress of drug-loaded polymeric micelles into clinical studies. J. Controlled Release 190, 465–476 (2014).
Gohy, JF & Zhao, Y Photo-responsive block copolymer micelles: design and behavior. Chem. Soc. Rev. 42, 7117–7129 (2013).
Soleymani, AH, Vakili, MR, Shafaati, A & Lavasanifar, A Block Copolymer Stereoregularity and Its Impact on Polymeric Micellar Nanodrug Delivery. Mol. Pharm. 14, 2487–2502 (2017).
Gohy, J.F. Block Copolymer Micelles. Adv. Polym. Sci. 190, 65–136 (2005).
Hamley, IW Nanotechnology with Soft Materials. Angew. Chem., Int. Ed. 42, 1692–1712 (2003).
Schacher, FH, Rupar, PA & Manners, I Functional Block Copolymers: Nanostructured Materials with Emerging Applications. Angew. Chem., Int. Ed. 51, 7898–7921 (2012).
Harada, A & Kataoka, K Formation of polyion complex micelles in an aqueous milieu from a pair of oppositely-charged block copolymers with poly(ethylene glycol) segments. Macromolecules 28, 5294–5299 (1995).
Kataoka, K, Togawa, H, Harada, A, Yasugi, K, Matsumoto, T & Katayose, S Spontaneous formation of polyion complex micelles with narrow distribution from antisense oligonucleotide and cationic block copolymer in physiological saline. Macromolecules 29, 8556–8557 (1996).
Katayose, S & Kataoka, K Water-Soluble Polyion Complex Associates of DNA and Poly(ethylene glycol)-Poly(L-lysine) Block Copolymer. Bioconjugate Chem 8, 702–707 (1997).
Harada, A & Kataoka, K Novel polyion complex micelles entrapping enzyme molecules in the core: Preparation of narrowly-distributed micelles from lysozyme and poly(ethylene glycol)-poly(aspartic acid) block copolymer in aqueous medium. Macromolecules 31, 288–294 (1998).
Harada, A & Kataoka, K On-off control of enzymatic activity synchronizing with reversible formation of supramolecular assembly from enzyme and charged block copolymers. J. Am. Chem. Soc. 121, 9241–9242 (1999).
Kakizawa, Y, Harada, A & Kataoka, K Environment-sensitive stabilization of core-shell structured polyion complex micelle by reversible cross-linking of the core through disulfide bond. J. Am. Chem. Soc. 121, 11247–11248 (1999).
Kataoka, K, Harada, A & Nagasaki, Y Block copolymer micelles for drug delivery: design, characterization and biological significance. Adv. Drug Del. Rev 47, 113–131 (2001).
Harada, A & Kataoka, K Supramolecular assemblies of block copolymers in aqueous media as nanocontainers relevant to biological applications. Prog. Polym. Sci. 31, 949–982 (2006).
Cabral, H, Nishiyama, N & Kataoka, K Supramolecular nanodevices: From design validation to theranostic Nanomedicine. Acc. Chem. Res. 44, 999–1008 (2011).
Itaka, K & Kataoka, K Progress and prospects of polyplex nanomicelles for plasmid DNA delivery. Current Gene Therapy 11, 457–465 (2011).
Gohy, JF, Varshney, SK, Antoun, S & Jerome, R Water-Soluble Complexes Formed by Sodium Poly(4-styrenesulfonate) and a Poly(2-vinylpyridinium)-block-poly(ethyleneoxide) Copolymer. Macromolecules 33, 9298–9305 (2000).
Gohy, JF, Varshney, SK & Jerome, R Water-Soluble Complexes Formed by Poly(2-vinylpyridinium)-block-poly(ethylene oxide) and Poly(sodium methacrylate)-block-poly(ethylene oxide) Copolymers. Macromolecules 34, 3361–3366 (2001).
Li, Y, Bronich, TK, Chelushkin, PS & Kabanov, AV Dynamic Properties of Block Ionomer Complexes with Polyion Complex Cores. Macromolecules 41, 5863–5868 (2008).
Luo, K, Yin, J, Song, Z, Cui, L, Cao, B & Chen, X Biodegradable Interpolyelectrolyte Complexes Based on Methoxy Poly(ethylene glycol)-b-poly(α, L-glutamic acid) and Chitosan. Biomacromolecules 9, 2653–2661 (2008).
Yusa, S, Yokoyama, Y & Morishima, Y Synthesis of Oppositely Charged Block Copolymers of Poly(ethylene glycol) via Reversible Addition-Fragmentation Chain Transfer Radical Polymerization and Characterization of Their Polyion Complex Micelles in Water. Macromolecules 42, 376–383 (2009).
Novoa-Carballal, R, Pergushov, DV & Muller, AHE Interpolyelectrolyte complexes based on hyaluronic acid-block-poly(ethylene glycol) and poly-L-lysine. Soft Matter 9, 4297–4303 (2013).
van der Burgh, S, Keizer, A & Stuart, MAC Complex Coacervation Core Micelles. Colloidal Stability and Aggregation Mechanism. Langmuir 20, 1073–1084 (2004).
Liu, Y, Li, C, Wang, HY, Zhang, XZ & Zhuo, RX Synthesis of Thermo- and pH-Sensitive Polyion Complex Micelles for Fluorescent Imaging. Chem. Eur. J 18, 2297–2304 (2012).
Nakai, K, Nishiuchi, M, Inoue, M, Ishihara, K, Sanada, Y, Sakurai, K & Yusa, S Preparation and Characterization of Polyion Complex Micelles with Phosphobetaine Shells. Langmuir 29, 9651–9661 (2013).
Voets, IK, Moll, PM, Aqil, A, Jerome, C, Detrembleur, C, de Waard, P, de Keizer, A & Cohen, SMA Temperature Responsive Complex Coacervate Core Micelles With a PEO and PNIPAAm Corona. J. Phys. Chem. B 112, 10833–10840 (2008).
De Santis, S, Diana, LR, Diociaiuti, M & Masci, G Pegylated and Thermosensitive Polyion Complex Micelles by Self-Assembly of Two Oppositely and Permanently Charged Diblock Copolymers. Macromolecules 43, 1992–2001 (2010).
Voets, IK, de Keizer, A, Cohen S, MA, Justynska, J & Schlaad, H Irreversible Structural Transitions in Mixed Micelles of Oppositely Charged Diblock Copolymers in Aqueous Solution. Macromolecules 40, 2158–2164 (2007).
Harada, A & Kataoka, K Effect of charged segment length on physicochemical properties of core-shell type polyion complex micelles from block ionomers. Macromolecules 36, 4995–5001 (2003).
Koide, A, Kishimura, A, Osada, K, Jang, WD, Yamasaki, Y & Kataoka, K Semipermeable Polymer Vesicle (PICsome) Self-Assembled in Aqueous Medium from a Pair of Oppositely Charged Block Copolymers: Physiologically Stable Micro-/Nanocontainers of Water-Soluble Macromolecules. J. Am. Chem. Soc. 128, 5988–5989 (2006).
Anraku, Y, Kishimura, A, Yamasaki, Y & Kataoka, K Living Unimodal Growth of Polyion Complex Vesicles via Two-Dimensional Supramolecular Polymerization. J. Am. Chem. Soc. 135, 1423–1429 (2013).
Harada, A & Kataoka, K Chain length recognition: Core-shell supramolecular assembly from oppositely charged block copolymers. Science 283, 65–67 (1999).
Hayashi, K, Chaya, H, Fukushima, S, Watanabe, S, Takemoto, H, Osada, K, Nishiyama, N, Miyata, K & Kataoka, K Influence of RNA Strand Rigidity on Polyion Complex Formation with Block Catiomers. Macromol. Rapid Commun. 37, 486–493 (2016).
Yi, Y, Kim, H-J, Mi, P, Zheng, M, Takemoto, H, Toh, K, Kim, B-S, Hayashi, K, Naito, M, Matsumoto, Y, Miyata, K & Kataoka, K Targeted systemic delivery of siRNA to cervical cancer model using cyclic RGD-installed unimer polyion complex-assembled gold nanoparticles. J. Control. Release 244, 247–256 (2016).
Kim, H-J, Takemoto, H, Yi, Y, Zheng, M, Maeda, Y, Chaya, H, Hayashi, K, Mi, P, Pittella, F, Christie, RJ, Toh, K, Matsumoto, Y, Nishiyama, N, Miyata, K & Kataoka, K Precise engineering of siRNA delivery vehicles to tumors using polyion complexes and gold nanoparticles. ACS Nano 8, 8979–8991 (2014).
The authors declare no conflict of interest.
About this article
Cite this article
Harada, A., Kataoka, K. Polyion complex micelle formation from double-hydrophilic block copolymers composed of charged and non-charged segments in aqueous media. Polym J 50, 95–100 (2018). https://doi.org/10.1038/pj.2017.67
Poly(α-l-lysine)-based nanomaterials for versatile biomedical applications: Current advances and perspectives
Bioactive Materials (2021)
100th Anniversary of Macromolecular Science Viewpoint: Attractive Soft Matter: Association Kinetics, Dynamics, and Pathway Complexity in Electrostatically Coassembled Micelles
ACS Macro Letters (2021)
Angewandte Chemie International Edition (2021)
Current Opinion in Colloid & Interface Science (2021)