copolymers. We focus on their applications in medicine, as drug delivery carriers, biological response modifiers, and pharmaceutical ingredients. Examples of drug delivery systems and formulations currently in clinical use, clinical trials or preclinical development are highlighted. We also discuss the role that Pluronic® copolymers may play in the innovative design of new nanomedicines in the near future.

Assemblies of polylactide-based amphiphiles in alcohols are shown to give unprecedented shape selectivity based on unimer solubility, leading to the formation of large uniform 2D diamond-shaped platelets, up to several microns in size.

Co-crystallization of polymers with different configurations/tacticities provides access to materials with enhanced performance. The stereocomplexation of isotactic poly(L-lactide) and poly(D-lactide) has led to improved properties compared with each homochiral material. Herein, we report the preparation of stereocomplex micelles from a mixture of poly(L-lactide)-b-poly(acrylic acid) and poly(D-lactide)-b-poly(acrylic acid) diblock copolymers in water via crystallization-driven self-assembly. During the formation of these stereocomplex micelles, an unexpected morphological transition results in the formation of dense crystalline spherical micelles rather than cylinders. Furthermore, mixture of cylinders with opposite homochirality in either THF/H2O mixtures or in pure water at 65 °C leads to disassembly into stereocomplexed spherical micelles. Similarly, a transition is also observed in a related PEO-b-PLLA/PEO-b-PDLA system, demonstrating wider applicability. This new mechanism for morphological reorganization, through competitive crystallization and stereocomplexation and without the requirement for an external stimulus, allows for new opportunities in controlled release and delivery applications.

A series of poly(L-lactide)-b-poly(acrylic acid) (PLLA-b-PAA) diblock copolymers with a range of hydrophobic or hydrophilic block lengths were designed in order to tune the size of the resultant cylindrical micelles using a crystallization-driven self-assembly (CDSA) approach. The precursor poly(L-lactide)-b-poly(tetrahydropyran acrylate) (PLLA-b-PTHPA) was synthesized by a combination of ring-opening polymerization (ROP) and reversible additionfragmentation chain transfer (RAFT) polymerization. The CDSA process was carried out in a tetrahydrofuran/water (THF/H 2 O) mixture during the hydrolysis of PTHPA block at 65 °C using an evaporation method. A majority of PLLA-b-PAA diblock copolymers resulted in the formation of cylindrical micelles with narrow size distributions (L w /L n < 1.30) as determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Furthermore, the length of PLLA block was found to control the length of the resultant cylindrical micelles while the length of PAA block governed their widths. Synchrotron small-angle X-ray scattering (SAXS) further proved that the length increase of these cylinders was a consequence of the decreasing PLLA block lengths. The crystalline core nature of these cylinders was characterized by wide-angle X-ray diffraction (WAXD), and the relative core crystallinity was calculated to compare different samples. Both the hydrophobic weight fraction and the relative core crystallinity were found to determine the geometry of the formed PLLA-b-PAA cylindrical micelles. Finally, changing the pH conditions of the CDSA process was found to have no significant effect on tuning the resultant dimensions of the cylinders.

The synthesis of nucleobase-containing polymers was successfully performed by RAFT dispersion polymerization in both chloroform and 1,4-dioxane and self-assembly was induced by the polymerizations.

The synthesis and self-assembly of thymine-containing polymers were performed using RAFT dispersion polymerization. A combination of microscopy and scattering techniques was used to analyze the resultant complex morphologies. The primary observation from this study is that the obtained aggregates induced during the polymerization were well-defined despite the constituent copolymers possessing broad dispersities. Moreover, a variety of parameters, including the choice of polymerization solvent, the degree of polymerization of both blocks and the presence of an adenine-containing mediator, were observed to affect the resultant size and shape of the assembly.

We report the crystallization-driven self-assembly of diblock copolymers bearing a poly(L-lactide) block into cylindrical micelles. Three different hydrophilic corona-forming blocks have been employed: poly(4acryloyl morpholine) (P4AM), poly(ethylene oxide) (PEO) and poly(N,N-dimethylacrylamide) (PDMA).Optimization of the experimental conditions to improve the dispersities of the resultant cylinders through variation of the solvent ratio, the polymer concentration, and the addition speed of the selective solvent is reported. The last parameter has been shown to play a crucial role in the homogeneity of the initial solution, which leads to a pure cylindrical phase with a narrow distribution of length. The hydrophilic characters of the polymers have been shown to direct the length of the resultant cylinders, with the most hydrophilic corona block leading to the shortest cylinders.

We report a simple temperature-responsive bioconjugate system comprising superfolder green fluorescent protein (sfGFP) decorated with poly[(oligo ethylene glycol) methyl ether methacrylate] (PEGMA) polymers. We used amber suppression to site-specifically incorporate the non-canonical azide-functional amino acid p-azidophenylalanine (pAzF) into sfGFP at different positions. The azide moiety on modified sfGFP was then coupled using copper-catalyzed “click” chemistry with the alkyne terminus of a PEGMA synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization. The protein in the resulting bioconjugate was found to remain functionally active (i.e., fluorescent) after conjugation. Turbidity measurements revealed that the point of attachment of the polymer onto the protein scaffold has an impact on the thermoresponsive behavior of the resultant bioconjugate. Furthermore, small-angle X-ray scattering analysis showed the wrapping of the polymer around the protein in a temperature-dependent fashion. Our work demonstrates that standard genetic manipulation combined with an expanded genetic code provides an easy way to construct functional hybrid biomaterials where the location of the conjugation site on the protein plays an important role in determining material properties. We anticipate that our approach could be generalized for the synthesis of complex functional materials with precisely defined domain orientation, connectivity, and composition.