Light-Initiated in Situ Self-Assembly (LISA) from Multiple

Article pubs.acs.org/Macromolecules

Light-Initiated in Situ Self-Assembly (LISA) from Multiple Homopolymers Liang Chen,† Miaomiao Xu,† Jun Hu,*,‡ and Qiang Yan*,† †

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China ‡ State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China S Supporting Information *

ABSTRACT: Almost all of polymeric nanostructures are now prepared by a classical post-self-assembly strategy. An ambitious target is to quest new polymer in situ self-assembly ways. Here we pose a light-initiated in situ self-assembly method, named LISA, which can de novo form various nanostructures through orthogonal photoligation from multiple homopolymers. Tuning the initial componential or light parameter, one can predict and govern the systematic morphological evolution. This method circumvents tedious synthesis and solution-processing procedures of block copolymers in post-self-assembly strategy and allows the preparation of ordered assemblies from simple homopolymers in one-pot photoreaction. We anticipate that this photocontrolled in situ self-assembly strategy would provide a new vision for facile construction of high-ordered nanostructures starting from homopolymers realize in situ self-assembly is unexplored.26 Here we describe a universal and highly efficient approach for de novo generation of polymer nanostructures by means of an orthogonal photoligation. o-Methylbenzaldehyde (MB) is a kind of typical photoenolization molecule, which can be isomerized to oquinodimethane (QD) form and undergo a light-triggered [4 + 2]-cycloaddition with electron-poor ene, such as maleimide (MI, Scheme 1a).27,28 We found that this photoreaction, unlike other similar ones, has a high chemical tolerance to protic solvents (e.g., H2O), which offer the possibility to facilitate an aqueous self-assembly. Based on this, commercially available poly(ethylene glycol), polylactide, and poly(ε-caprolactone) were terminated with photoactivatable MB or electron-deficient MI to afford three end-capped homopolymers (PEG-MB, PLAMI, and PCL-MI). Adding PEG-MB into PLA-MI or PCL-MI, the photoligation mediates the binary mixture to in situ form purely spherical or vesicular phases in a relatively concentrated aqueous solution (10 wt %), respectively. Mixing the three homopolymers with various fractions, a sequence of nanoobjects with tunable geometries can be generated via this “onepot” photoreaction. Furthermore, tuning the initial parameters, one can predict the phase diagram of tricomponent system and control their kinetic morphological evolution (Scheme 1b). It is expected that this light-initiated in situ self-assembly, we called LISA, could provide a new possibility to directly construct intricate nanostructures by only using simple homopolymers.

1. INTRODUCTION Since the studies on block copolymer self-assembly began in the 1960s,1 a variety of polymer nanostructures, such as spheres, worms, vesicles, toroids, and lamellae, have been fabricated.2−5 These high-ordered nano-objects in solution are principally prepared by a post-self-assembly strategy; that is, we need to first synthesize and purify block copolymers and subsequently dissolve them in selective solvents to form aggregates.6 Although this classical technique lays the foundation for current soft nanotechnology7 and material science,8 it has a concentration limit (140): their widths evaluate to be 35 nm, and their lengths exceed ∼5 μm. DLS results showed their hydrodynamic diameter of 330 nm (Figure 2d, purple curve), and the gyration radius (Rg) of these aggregates was ∼298 nm determined by SLS. In this case, the ρ value was calculated to be 1.806, corresponding to the theoretical value (ρT = 1.732) of a cylindrical model.29 The drastic raise of solution shear viscosity (η0) also supported the worm formation (Figure S9).30 A plausible reason for producing single pure phase rather than mixed phase is that the favorable miscibility of two polyester blocks31 (PLA and PCL) can result in a coassembly behavior between PEG-b-PLA and PEG-b-PCL (Figure S8c). To further ensure that these worm-like micelles are formed from the coassembly of PEG-MB, PLA-MI, and PCL-MI, we adopted a fluorescent probe method. Two fluorescent labelanchored homopolymers, PLA-MI using fluorescein dye as headgroup (FAM-PLA-MI, λex = 495 nm, λem = 520 nm) and PCL-MI using cyanine dye as headgroup (Cy3-PCL-MI, λex = 545 nm, λem = 570 nm), were designed and synthesized. Since the emission wavelength of FAM label is close to the excitation wavelength of the Cy3 label, once the two kinds of dyes together confine in a hydrophobic nanodomain, a strong Förster resonance energy transfer (FRET) effect will occur, quenching the fluorescence. On the basis of this principle, we surveyed the fluorescent changes under different coassembly conditions. The spherical micelles formed by PEG-MI and FAM-PLA-MI binary system showed a strong emission at 520 nm, and the vesicular aggregates formed by PEG-MI and Cy3PCL-MI binary system gave a characteristic emission around 570 nm. However, the fluorescence of the triple system, PEGMI/FAM-PLA-MI/Cy3-PCL-MI, was greatly depressed (Figure S10), which indicates that the resulted worm-like micelles indeed contain the two components of FAM-PLA-MI and Cy3PCL-MI homopolymers. Photocontrolled in Situ Morphological Evolution. On the basis of these discoveries, it seems that varying the initial parameters of multiple homopolymers (e.g., ingredients), one can dictate their final in situ self-assembly morphologies. To further validate this concept, we tracked their shape transformation by tuning the molar ratios of homopolymers. We defined r as the PCL-MI molar ratio (r = nPCL‑MI/nPLA‑MI). When r is only 0.05, spherical micelles are still the main phase, while a little bit of worms begin to appear (indicated by arrows in Figure 3a). On close inspection of Figure 3a, these short worms are formed by the fusion of several spheres into oligomers. In contrast, previous works have reported the micellar fusion phenomena, but only when exerted irritants or salts.32,33 Such a photoreaction-induced sphere-to-worm transition is unprecedented. Further increasing the ratio of PCL-MI (r = 0.1 and 0.2), the population of worms rises at the expense of a reduction of sphere quantity (Figure 3b,c). Moreover, the lengths of these worms are gradually elongated, presumably ascribing to the head-to-end coalescence of short worms. Purely nanofibrous phase can be acquired when r value is 1.0 (Figure 3d). However, at this time some branch points are formed in these fibers (indicated by arrows in Figure 3d). Figure 3e shows that these branched structures can further coalesce and morph to octopus-like nanoobjects with budding “tentacles” (indicated by red arrow) and small vesicles (indicated by yellow arrow, r = 5). Similar octopi-like aggregates are also observed in the PISA method,11 but in that case the advent of vesicular phase is lagging. It means that

Figure 2. (a) TEM images and DLS changes obtained for lightinitiated in situ self-assembly of binary and ternary homopolymers: (a) spheres from PEG-MB/PLA-MI system (1/1); (b) vesicles from PEGMB/PCL-MI system (1/1), inset: single-vesicle membrane structure; (c) worms from PEG-MB/PLA-MI/PCL-MI system (2/1/1); and (d) hydrodynamic diameters of the three kinds of aggregates. (The homopolymers were mixed in DMF/H2O (3/1, v/v) at 10% solid concentrations and then exposed to 320 nm irradiation for 1 h to directly form aggregates. Scale bar is 500 nm.)

Kinetic studies revealed that this self-assembly process is synchronous with the photoreaction, as judged by the identical variation tendency of the degree of coupling reaction and the growth of spheres (Figure S7). For another binary system (PEG-MB/PCL-MI = 1/1), the light can direct them to become pure vesicular phase with the sizes of 95 ± 25 nm (Figure 2b). DLS results showed that their hydrodynamic diameters were ∼91 nm (Figure 2d, green curve), and static light scattering (SLS) further showed their gyration radius (Rg) was determined to be ∼49 nm. The shape factor, ρ = Rg/Rh, was used as a sensitive parameter to identify the geometry of polymer aggregate. In the case, the ρ value was calculated to be 1.062, which is close to the theoretical value of a hollow spherical model (ρT ∼ 1).29 In comparison to the PEG-MB/ PLA-MI system, such a shape difference is reasonable because the chain length of hydrophobic PCL is 6-fold longer than that of PLA. Thus, a bilayer packing fashion is theoretically favored (Figure S8b).3 It is noteworthy that all of the aggregates can be acquired in relatively concentrated solution (10 wt % solid), which breaks through the concentration limit of conventional post-self-assembly. The above results have proven that light is capable of in situ initiating self-assembly of two homopolymers. Then we wondered what happens for the more complex tricomponent system (e.g., PEG-MB/PLA-MI/PCL-MI)? To elucidate this, we set the total molar amount of PLA-MI and PCL-MI equal to that of PEG-MB to ensure that all homopolymers are converted to copolymers. Empirically, the two amphiphilic photoproducts (PEG-b-PLA and PEG-b-PCL) should lead to the emergence of two types of discrete aggregates (spheres and vesicles). However, it is surprising that the eventual structure dominated in solution is one-dimensional worm-like micelles when the initial content of PLA-MI is equal to PCL-MI (Figure 2c). C

DOI: 10.1021/acs.macromol.7b00505 Macromolecules XXXX, XXX, XXX−XXX

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Macromolecules

worm and from worm to vesicle, respectively. The ergodic shape evolution could be summarized in Table S1. On the other hand, the positive shift of phase regions mediated by light wavelength is also explainable: because the chain length of PLA-MI is much shorter than PCL-MI, PLA-MI can be preferentially reacted by high-energy radiation (310 nm vs 365 nm); thereby, the real r value under 310 nm condition is somewhat lower than that under 365 nm, which will cause a shift of phase windows in dependence on wavelength. The popular PISA way can attain similar aims by tuning polymerization degree; in contrast, this present LISA method manipulates the phase behaviors by modulating light and/or componential parameters, which can help us enhance in situ controllability and tunability.

3. CONCLUSIONS In conclusion, we have demonstrated the first paradigm for light-initiated in situ self-assembly (LISA). It can allow simple homopolymers to de novo form regular nanostructures through a facile photoligation. Presetting the initial photo- and component factors, a variety of pure polymer morphologies can be predictably and reproducibly acquired. As compared to PISA based on the synchronism of living polymerization and micellar growth, this LISA method relies on a distinct mechanism based on the concurrence of photochemical coupling and self-assembly process. This alternative way can solve the long-term problems of post-self-assembly (such as concentration limit and block copolymer syntheses) and overcome the weakness of PISA on multiple polymer system. Meanwhile, we notice that a constraint of this method lies in hard to deal with high-molecule-weight homopolymers (>50 kDa) because of their poor solubility. Ongoing work is optimizing this issue. Despite a few blemishes, this new methodology would illumine a direction of reaction-induced in situ self-assembly.

Figure 3. Detailed shape evolution from ternary homopolymers (PEGMB/PLA-MI/PCL-MI) upon different componential ratios (r = nPCL‑MI/nPLA‑MI): (a) spheres and a little bit of worms (r = 0.05); (b, c) the amount of spheres decreasing and worms increasing, and meanwhile the worms transform from short rods to long fibers (r = 0.1 and 0.2); (d) pure worm phase (r = 1.0); (e) worms, small vesicles, and octopus-like micelles in a multiphasic state (r = 5.0); (f) interconnected membrane structure (r = 10.0); (g) nascent vesicles (r = 20.0) (scale bar is 200 nm). (h) Phase diagram of light-initiated in situ self-assembly of tricomponent homopolymers in concentrated solution against the change of homopolymer ratios and light wavelengths. (The total molar amounts of PCL-MI and PLA-MI are equal to that of PEG-MB.)

our system can experience a complex multiphase state. Thereafter, the tentacles serve as arms to intersect their parent membranes (Figure 3f). When the r reaches up to 20, the membranes enclose and we can see the rudiment of large vesicles (Figure 3g). We conjectured that the vesicular structure is the evolutionary end point of this tricomponent in situ selfassembly because no other shapes were seized. On the other hand, we wanted to know whether light parameters can affect this process. Tuning the optical wavelength has negligible impacts on this ergodic phase transition, but the wavelength increase (310 nm → 365 nm) can lead to a positive shift of whole phase regions. Overall, the phase diagram among tricomponent self-assembly can be depicted in Figure 3h. Using it as a predictive roadmap can guide us to facilely prepare a sequence of nanostructures in a one-pot photochemical path. Light-Initiated Multicomponent Homopolymer in Situ Self-Assembly Mechanism. After drawing the self-assembly graph, we posed a possible mechanism to explain how light drives the de novo generation of diversiform polymer nanoobjects. In general, the polymeric geometry can be predicted on the value of hydrophilic volume fraction (f v):3 spherical micelles can be formed when f v > 50%, cylinders when 40% < f v < 50%, and lamellar structures for 25% < f v < 40%. In the tricomponent system, only PEG-MB has contribution to the hydrophilicity. By varying the initial r factor, we can estimate the continuous changes of f v values. Experimentally, the phase boundaries of pure sphere, worm, and vesicle are in r ≤ 0.05, 0.3 ≤ r ≤ 2, and r ≥ 20, respectively (Figure 3h, 320 nm light). Hence, the actual hydrophilic ratios among the final aggregates are f v ≥ 54%, 37% ≤ f v ≤ 47%, and f v ≤ 32% (see Supporting Information), respectively, which are basically coincident with the theoretical expectation. In other r intervals (0.05 < r < 0.3 and 2 < r < 20), the f vs ranges from 47% to 54% and from 32% to 37%, corresponding to the transitional zones from sphere to

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.7b00505.

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Detailed synthesis and characterization of polymers, photoligation, and in situ self-assembly process (PDF)

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (Q.Y.). ORCID

Qiang Yan: 0000-0001-5523-2659 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work is financially supported by the National Natural Science Foundation (21674022), the Grant of Chinese Recruitment Program of Global Experts (KHH1717002), and Open Research Fund of State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. D

DOI: 10.1021/acs.macromol.7b00505 Macromolecules XXXX, XXX, XXX−XXX

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DOI: 10.1021/acs.macromol.7b00505 Macromolecules XXXX, XXX, XXX−XXX