Tritschler, U., Pearce, S., Gwyther, J., Whittell, G., & Manners, I.
(2017). 50th Anniversary Perspective: Functional Nanoparticles from
the Solution Self-Assembly of Block Copolymers.
Macromolecules
,
50
, 3439-3463. https://doi.org/10.1021/acs.macromol.6b02767
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1
Perspective:
Functional Nanoparticles from the Solution Self-Assembly of Block
Copolymers
Ulrich Tritschler, Sam Pearce, Jessica Gwyther, George Whittell, and Ian Manners*
School of Chemistry, University of Bristol, Bristol BS8 1TS, United Kingdom
Abstract.
This Perspective outlines recent advances concerning the formation and potential uses of
block copolymer micelles, a class of soft matter-based nanoparticles of growing importance.
As a result of rapidly expanding interest since the mid 1990s, substantial advances have been
reported in terms of the development of morphological diversity and complexity, control over
micelle dimensions, scale up, and applications in a range of areas from nanocomposites to
nanomedicine.
2
1. Introduction
The solution self-assembly of block copolymers (BCPs), which consist of covalently linked,
and more recently non-covalently linked, macromolecular building blocks, represents an
important method for the creation of soft matter-based core-shell nanoparticles (micelles) with
useful properties and functions.
1-17
A precisely designed BCP architecture is a key
prerequisite for controlling the solution self-assembly process by tuning the interactions
between the different polymer segments, both with each other, and the solvent.
1, 6, 18
Well-
defined BCPs, such as diBCPs, linear and star triBCPs, are now accessible via a variety of
living polymerization techniques, including anionic polymerization and controlled radical
polymerization methods, such as reversible addition-fragmentation chain transfer (RAFT)
polymerization, nitroxide mediated living radical polymerization (NMP), and atom transfer
radical polymerization (ATRP).
19, 20
The discovery of the living anionic polymerization in the
1950s was a key milestone for the preparation of synthetic BCPs
21, 22
and the first solution
self-assembly studies on BCPs followed in the early 1960s.
23, 24
More recently, controlled
radical polymerization techniques have played a pivotal role by permitting a marked
expansion of the range of BCP chemistries and thereby micelle functionality accessible.
25-30
In this Perspective we focus on recent developments concerning the self-assembly of BCPs in
solvents that are selective for one or more of the blocks. After a brief overview of factors that
generally influence the micelle morphology and dimensions during the solution self-assembly
process (section 2), we focus on different approaches to the formation of BCP micelles. This
includes the solution self-assembly of BCPs into micelles with amorphous cores (section 3),
as well as micelles with crystalline cores (section 4). In section 5 we discuss the in-situ
polymerization and solution self-assembly of amphiphilic BCPs, which is an emerging
method for the large scale preparation of BCP micelles. Section 6 focuses on potential
applications. Throughout we provide an overview of these topics by the discussion of
3
selected, representative examples.
A discussion of the solution self-assembly of polypeptide
amphiphiles, as well as properties and applications of polypeptide-based nanoparticles are
beyond the scope of this review and the reader is referred to the relevant literature.
31-36
2. Factors that Influence Micelle Morphology
The self-assembly of molecular amphiphiles, such as low molar mass surfactants or lipids, to
yield micelles in water is mainly driven by the increase in entropy associated with the
expulsion of solvating molecules.
37
This enables the insoluble hydrophobic tails of the
amphiphiles to aggregate, thereby minimising enthalpically unfavourable hydrophobe-water
interactions and leading to a further reduction in the total free energy of the system. Micelle
formation occurs above a specific equilibrium concentration, termed the critical micelle
concentration (CMC). How the amphiphiles pack into the micelle, and hence the morphology
formed, is related to the amphiphile shape which depends on the relative size of the
hydrophobic and hydrophilic parts under equilibrium self-assembly conditions as this
determines the curvature of the hydrophilic/hydrophobic interface. The packing preferences
can be analysed in terms of the dimensionless “packing parameter” P, which is defined as:
𝑃 =
𝑣
𝑎
0
𝑙
𝑐
where v is the volume of the hydrophobic hydrocarbon chain, a
0
is the area of the hydrophilic
head group, and l
c
is the length of the hydrophobic tail normal to the interface (Figure 1).
Typically, spherical micelles are favoured for P ≤ 1 3
⁄
, cylindrical (also known as worm-like
or rod-like) micelles for 1 3
⁄
≤ P ≤ 1 2
⁄
, vesicles for 1 2
⁄
≤ P ≤ 1.
38, 39
It is noteworthy that
this geometric approach makes a prediction of the equilibrium morphology, which is
generally accessible with molecular amphiphiles on account of rapid exchange between the
aggregated (micelle) and molecularly dissolved (unimer) state.
4
Figure 1. The thermodynamically-preferred morphology of the self-assembled BCPs in a selective
solvent can be predicted by means of the dimensionless “packing parameter” P. Reproduced with
permission from ref.
1
(copyright 2009 Wiley-VCH).
As with the case of molecular amphiphiles, BCPs can self-assemble into micelles with core-
shell structures in selective solvents above the CMC. Morphologies, such as spheres,
cylinders (or worms or rods), and vesicles, are also commonly observed (Figure 1).
2-6, 18, 40, 41
The micelle core is formed by the insoluble, solvophobic block(s) and the corona (or shell) by
the soluble solvophilic block(s), which leads to colloidal stabilization of the micelle in
solution.
3, 42-46
The role of entropy in self-assembly, however, is smaller (especially in non-
aqueous solvents), as a result of the reduced translational freedom of macromolecules with
respect to low molar mass species.
37
There is, nonetheless, an unfavourable entropic
contribution from the stretching of the solvophobic chains within the micellar core. The
reduction in interfacial energy between the core-forming block and the solvent, and the
presence of repulsive interactions between the solvophilic coronal chains which cause
stretching constitute additional opposing enthalpic and entropic contributions to the free
energy of the system, respectively. In practice, the thermodynamically preferred micelle
morphology often mainly depends on the volume fractions of the solvophobic and solvophilic
