Bottlebrush-Colloid Janus Nanoparticles | ACS Macro Letters

Jun 4, 2019 - A bottlebrush-colloid Janus nanoparticle (JNP) with a ball-and-stick structure is reported. A single poly(4-vinyl benzyl chloride) (PVBC...
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Letter Cite This: ACS Macro Lett. 2019, 8, 737−742

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Bottlebrush-Colloid Janus Nanoparticles Jingyun Jing,†,§ Bingyin Jiang,*,† Fuxin Liang,†,‡ and Zhenzhong Yang*,‡,† †

State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China ‡ Institute of Polymer Science & Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China § University of Chinese Academy of Sciences, Beijing 100049, China

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S Supporting Information *

ABSTRACT: A bottlebrush-colloid Janus nanoparticle (JNP) with a ball-and-stick structure is reported. A single poly(4-vinyl benzyl chloride) (PVBC) polymer chain was grafted onto the amine-capped Fe3O4@NH2 nanoparticle. pH-responsive 2diethylaminoethyl methacrylate (DEAEMA) and water-soluble oligo(ethylene glycol) methacrylate (OEGMA) were sequentially grown from the PVBC backbone by ATRP, forming a core−shell bottlebrush. The synthesized PVBC208-g(PDEAEMA13-b-POEGMA8)-Fe3O4@NH2 JNPs are dispersible in water and can be manipulated by a magnet. The Fe3O4 NPs with exposed −NH2 groups facilitate accumulation at acidic sites. Hydrophobic dyes can be loaded within the PDEAEMA at pH ≥ 7.5, while they are released at pH values below 6.8. The composite JNPs are promising as a guided pH-responsive delivery vector toward acidic solid tumors.

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Our group reported an effective approach for grafting single polymer chains onto chlorine-capped Fe3O4 NPs by a rapid termination of the anionic living polymer chain.17 Grafting of a single chain is ensured in principle when the polymer coil is sufficiently large and is greater than the NP diameter. The synthesis can be performed at a high solid content of ∼5%. This method is universal. We have recently described the grafting of a single polymer chain of cationic living poly(4-vinyl benzyl chloride) (PVBC) onto amine-group-capped Fe3O4 NPs.18 Tadpole Fe3O4@NH2 JNPs were generated. The single-chain-grafted JNPs will be useful for deriving other JNPs with various microstructures, such as the bottlebrush microstructure. A bottlebrush is similar to elongated worm-like polymeric micelles and can exhibit longer circulation time than its globular counterparts.19 In fact, polymeric bottlebrushes had been proven to be more effective as drug carriers.20−22 The polymeric bottlebrushes showed a greatly enhanced halflife of as long as 24 h in rats.23 Rod-like bottlebrushes have exhibited improved performance for cell uptake and penetration compared to their spherical and worm-shaped counterparts.24 However, these materials are purely organic polymers and lack the recognition and guidance capabilities. In this report, we describe the synthesis of a single bottlebrush-grafted JNP with multiple functionalities. As illustrated in Scheme 1, starting from PVBC-Fe3O4@NH2 JNPs, sequential ATRP was performed from the benzyl chloride side group of PVBC to polymerize 2-diethylaminoethyl methacrylate (DEAEMA) and oligo(ethylene glycol)

anus nanoparticles (JNPs) are an important category of nanomaterials since they are asymmetric in compositions and structures. 1,2 This allows the integration of the functionality of the nanoparticles and the performance of organic components such as polymer chains. Tadpole-shaped JNPs consisting of a polymer “tail” and a 10 nm nanoparticle (NP) “head” have attracted increasing interest.3 The head can be selected among inorganic,4 organic,5 and biological NPs such as proteins,6 while the polymer chain can be chosen to be either synthetic or biological.7 These JNPs are typically synthesized via two approaches. Intramolecular cross-linking of the desired segment of a block copolymer is an effective method.8 JNPs synthesized by this way are usually restricted to organic polymers.9 Alternatively, grafting polymer chains onto NP surfaces has become an attractive method.10 It is important to precisely control the number of grafted chains.11 Monofunctional polyhedral oligomeric silsesquioxane (POSS) and polyoxometalate (POM) have been extensively used as model NPs to graft single polymer chains via living radical polymerizations.12,13 These JNPs display fascinating selfassembly behaviors and unique supramolecular structures.14 However, the composition of the NPs (so-called giant “atoms”) is limited to a few types (POSS, C60, and POM). Extension of the functionalities to compositions beyond these giant “atoms” is challenging. Recently, the fabrication of a triblock JNP by wrapping a single Au NP with a triblock copolymer chain containing a 1,2-dithiolane-functionalized middle block was reported.15 The size and composition of the NPs and the block copolymers are strictly selected. Wang’s resin support synthesis has been shown to be a versatile method for the preparation of monofunctional NPs.16 The yield of the JNPs is rather low. © 2019 American Chemical Society

Received: March 29, 2019 Accepted: June 3, 2019 Published: June 4, 2019 737

DOI: 10.1021/acsmacrolett.9b00234 ACS Macro Lett. 2019, 8, 737−742

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ACS Macro Letters Scheme 1. Synthesis of the Responsive PVBC-g-(PDEAEMA-b-POEGMA)-Fe3O4@NH2 JNP

Figure 1. (a) DLS traces of the oleic-acid-capped Fe3O4 NP dispersion in toluene (1) and the amine-capped Fe3O4 NP dispersion in water (2). (b) FT-IR spectra of the oleic-acid-capped Fe3O4 NP (1) and the amine-capped Fe3O4 NP (2). (c) TEM images of the PVBC208-Fe3O4@NH2 JNP after drying the dispersion in DMSO. (d) A toluene/water emulsion stabilized with the JNP and collection with a magnet, with Sudan III added to dye the toluene for easier observation.

methacrylate (OEGMA). The PDEAEMA-b-POEGMA core/ shell bottlebrush was achieved. Our current ball-and-stickshaped JNPs can integrate the magnetism of Fe3O4 NPs with the pH-triggered release performance of PDEAEMA. These bottlebrushes are promising new candidate drug delivery vectors toward tumors. For PVBC208-Fe3O4@NH2 JNPs, representative oleic-acidcapped Fe3O4 NPs were synthesized as reported previously.25 The crystallinity of Fe3O4 was verified by XRD (Figure S1). Fe3O4 was paramagnetic with a saturation magnetization of 56.5 emu/g (Figure S2). The oleic-acid-stabilized Fe3O4 NPs showed a mass loss of 14.6% at 700 °C (Figure S3). The DLS results indicated that the NPs were well-dispersed in toluene without aggregation. The hydrodynamic diameter was measured to be 9.1 ± 0.5 nm, with a PDI of 0.19 ± 0.03 (Figure 1a-1). The NPs became dispersible in water after introducing the amine group onto the particle surface by ligand exchange with APEOS.26 The Fe3O4 NPs were coated with a layer of silica with the amine group facing outward. The aminecapped NPs displayed a lower saturation magnetization of 33.7 emu/g (Figure S4) and a mass loss of 34.7% at 700 °C (Figure S5). The DLS results showed that the hydrodynamic diameter was increased slightly to 11 nm (Figure 1a-2). The

characteristic peaks of the oleic-acid-capped NPs at 2922, 2852, and 1462 cm−1 were assigned to the −CH2− groups of the oleic acid (Figure 1b-1). After the ligand exchange with APEOS, new bands appeared at approximately 1000−1150 cm−1, indicating the formation of Si−O−Si bonds (Figure 1b2). The new peaks at 1589, 777, and 688 cm−1 were assigned to the amine group. The amine-capped NPs were well dispersed in water, forming a transparent dispersion that can be easily collected with a magnet (Figure S6). After drying the dispersion, the NPs remain as individual NPs, as shown by TEM (Figure S7). According to our previous report, single cationic polymer chain PVBC can be grafted onto an Fe3O4@ NH2 NP via termination if the chain coil length is large enough and greater than the NP diameter.18 The PVBC chain was polymerized by cationic polymerization (Mn = 31.9 kg/mol, Mw/Mn = 1.4, DP = 208) (Figure S8a). The hydrodynamic diameter (Dh) in dichloromethane was measured to be 9.5 nm by DLS (Figure S8b). Representative PVBC208-Fe3O4@NH2 JNPs were achieved in dichloromethane and collected with a magnet. After drying the dispersion in DMSO, the single PVBC chain tethered on the Fe3O4 NPs collapsed, displaying a parachute structure (Figure 1c). The JNPs contained 3.7 wt % PVBC according to TGA (Figure S8c). The JNPs were 738

DOI: 10.1021/acsmacrolett.9b00234 ACS Macro Lett. 2019, 8, 737−742

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ACS Macro Letters

Figure 2. (a) TEM image of the PVBC208-g-PDEAEMA13-Fe3O4@NH2 JNPs after drying the dispersion in DMSO at 70 °C. (b) DLS traces of the JNPs in water at 25 °C and at different pH values: pH = 4 (1) and pH = 8 (2). (c) DLS traces of the PVBC208-g-(PDEAEMA13-b-POEGMA8)Fe3O4@NH2 JNPs at pH = 4 (1) and pH = 10 (2). (d) TEM image of the JNPs after drying the dispersion and staining with iodine.

for the aggregation. The aggregates became smaller while heating the dispersion (Figure S18). At 70 °C, the DLS peak became narrow, corresponding to a size of 35 nm (Figure S19). After drying the dispersion at 70 °C, the NPs remained as individual particles, displaying a ball-and-stick structure (Figure 2a). The PVBC208-g-PDEAEMA13 bottlebrush rod had a length of ∼25 nm (inset of Figure 2a). On the other hand, the hydrogen bonding can be eliminated at lower pH values (e.g., pH = 4) since both PDEAEMA and amine groups are protonated. The JNPs were well dispersed in water regardless of the temperature. Within the range of 25−70 °C, the DLS peak remained narrow, corresponding to a size of ∼33 nm (Figure 2b-1). The NPs existed as individual particles. At a high pH above the pKa of ∼7.2 (e.g., pH = 8), PDEAEMA became hydrophobic, while the Fe3O4@NH2 NP surface remained hydrophilic. The DLS peak was quite broad, corresponding to a mean size of 342 nm (Figure 2b-2). Aggregates were observed by TEM (Figure S20). OEGMA was further grafted from PDEAEMA, forming a core−shell bottlebrush. The DP of the POEGMA block was measured to be ∼8 by 1H NMR (Figure S21). Here, the outer POEGMA provides a protective sheath. PVBC208-g-(PDEAEMA13-b-POEGMA8)-Fe3O4@NH2 JNPs were well dispersed in water over a broad pH range of 4−10. The dispersions were highly transparent (Figure S22). The DLS results showed that the JNPs existed as individual particles (Figure 2c). The hydrodynamic diameter decreased from 37 to 33 nm when the pH increased from 4 to 10. The inner PDEAEMA chain collapsed at pH = 10. The JNPs displayed the same ball-andstick structure in TEM images obtained after drying the dispersion (Figure S23). After selective staining of the inner PDEAEMA with iodine, the dark core can be distinguished from the gray shell (Figure 2d). The ball-and-stick structure

amphiphilic and could stabilize the sample toluene/water emulsions. The emulsion droplets could be easily collected with a magnet, leaving the transparent continuous aqueous phase (Figure 1d). Sudan III was added to dye toluene for easier observation. The emulsion droplet diameter was ∼2 μm according to LSCM (Figure S9). All of the amine side chains of the JNPs at the emulsion interface should face toward the aqueous phase. The amine side chains of the interface can be cross-linked with glutaraldehyde in water at a low pH value of 4 and become stable by reduction with NaBH4. A cryo-SEM image showed that the cross-linked droplet diameter was ∼2 μm (Figure S10). The NPs were closely packed at the monolayer interface with no voids. All of the JNPs adopted the same orientation at the interface. After toluene evaporation, the droplet shells remained intact but collapsed (Figure S11). The spherical shape can be recovered upon immersion in good solvents such as DMSO. By contrast, the as-prepared emulsion droplets broke apart into individual NPs upon addition of DMSO (Figure S12). For bottlebrush-colloid JNPs, bottlebrushes can be grafted from the PVBC backbone by ATRP.27 After grafting the representative pH-responsive polymer of PDEAEMA (pKa ∼ 7.2), the bottlebrush-colloid JNP of PVBC208-g-PDEAEMA13Fe3O4@NH2 was obtained. The ester carbonyl peak at 1725 cm−1 confirmed the presence of PDEAEMA (Figure S13). The JNP contained 11.6 wt % of PDEAEMA (Figure S14). The average DP of the grafted PDEAEMA side chain was measured to be 13 by 1H NMR analysis (Figure S15). At 25 °C, the bottlebrush-colloid JNP dispersion in DMSO appeared opaque. Aggregation of the dispersion was detected by DLS measurements (Figure S16). Large aggregates were observed by TEM (Figure S17). Hydrogen bonding between PDEAEMA and the amine group on the NP surface was responsible 739

DOI: 10.1021/acsmacrolett.9b00234 ACS Macro Lett. 2019, 8, 737−742

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Figure 3. pH-triggered loading and release of the PVBC208-g-(PDEAEMA13-b-POEGMA8)-Fe3O4@NH2 JNPs. The hydrophobic dye Sudan III was added to the toluene phase for easier observation. (a) Dispersion of the bottlebrush-colloid JNPs in a water/toluene mixture at different pH values (6−8) and release. (b) Release performance of the composite JNPs within a narrow pH range of 7.5−6.8.

was preserved. The JNPs contained 8.3 wt % POEGMA (Figure S24). The bottlebrush-colloid JNPs of PVBC208-g-(PDEAEMA13b-POEGMA8)-Fe3O4@NH2 can be used as a pH-triggered release delivery vector. JNPs (5 mg) were added into a toluene/water mixture (0.05 mL/1.5 mL) at different pH values to demonstrate this performance. Toluene was selectively dyed with Sudan III for easier observation. At pH 6, the NP is well-dispersed in the bottom aqueous phase, while toluene is the top phase (Figure 3a-1). At pH 8, the whole system becomes homogeneous, while the top toluene phase disappears (Figure 3a-2). The DLS peak is narrow, corresponding to a hydrodynamic diameter of 34 nm (Figure S25). The JNPs exist as individual particles in the dispersion. Toluene is absorbed inside the PDEAEMA core. It is understandable that the PDEAEMA core becomes hydrophobic at high pH above the pKa (∼7.2). The dyed toluene carried with the JNP can be delivered under the guidance by a magnet (Figure 3a-3). The JNPs are delivered to the bottom corner of the vessel with the magnet and are thus restricted to remain in that region. Upon lowering the pH to 6 by addition of acetic acid, toluene is released and diffuses outward (Figure 3a-4). Eventually, all of the toluene is released, forming a red oil top layer (Figure 3a-5). Once the magnetic restriction is removed, the JNPs are redispersed in water (Figure 3a-6). The pH-triggered release from the JNPs was further monitored by subtly adjusting the pH within the pH window of solid tumors. At pH 7.5 which is very close to the normal physiological pH ∼7.4, no dyed toluene is released after 12 h (Figure 3b-1). A slight decrease of the pH to 6.8 (corresponding to tumor pH) can drive the release (Figure 3b-2). Eventually, toluene is completely released, forming the top red oil layer (Figure 3b3). Similarly, the JNPs are redispersed in the bottom water phase upon the removal of the magnet, and the top oil phase floats (Figure 3b-4). We now demonstrate the targeting and controlled release of the composite PVBC 208 -g-(PDEAEMA 13 -b-POEGMA 8 )Fe3O4@NH2 JNPs. To mimic the acidic extracellular environment of human cancer tissues,28 a PAA hydrogel was synthesized (Figure 4a-1). Pores with diameters of ∼5 μm are interconnected after freeze-drying the hydrogel (Figure S26). At pH 6, all of the JNPs can be absorbed by the PAA hydrogel (Figure 4a-2). By contrast, some JNPs remain in water after the absorption at pH 8 (Figure 4a-3). After freezedrying the composite hydrogel (Figure 4a-2), the pore skeleton surface was coated with the NPs (Figure 4b). In contrast, the

Figure 4. (a-1) Aqueous dispersion of PVBC208-g-(PDEAEMA13-bPOEGMA8)-Fe3O4@NH2 JNPs and the PAA hydrogel; the dispersion and the hydrogel after absorption of the JNPs with the PAA hydrogel (a-2) at pH 6 and (a-3) pH 8. (b) SEM image of the JNP-absorbed composite PAA hydrogel at pH 6. (c,d) CLSM images showing the release of the dyed toluene from the composite PAA hydrogel (a-2) after 0.5 and 12 h. (e,f) CLSM images of the dyed toluene absorbed composite PAA hydrogel (a-3) after 0.5 and 12 h.

NPs form aggregates, filling the voids of another composite hydrogel (Figure S27). The peak at 1701 cm−1 assigned to the carboxyl group shifts to 1724 cm−1 after the absorption of the JNPs with the PAA hydrogel at pH 6 (Figure S28). It is reasonable to assume that the amine group at the NP surface forms a strong interaction with the carboxylic acid at the pore surface, favoring the absorption. CLSM observations show that some aggregates of the JNPs are irregular along the pore contour of the hydrogel, while other aggregates fill the voids (Figure 4c). At pH 6, the dyed toluene starts to be released. At a very early stage (e.g., 0.5 h), the amount released is rather low and negligible. All of the toluene is released after 12 h, and 740

DOI: 10.1021/acsmacrolett.9b00234 ACS Macro Lett. 2019, 8, 737−742

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(5) Zhou, F.; Xie, M.; Chen, D. Structure and Ultrasonic Sensitivity of the Superparticles Formed by Self-Assembly of Single Chain Janus Nanoparticles. Macromolecules 2014, 47, 365−372. (6) Ju, Y.; Zhang, Y.; Zhao, H. Fabrication of Polymer−Protein Hybrids. Macromol. Rapid Commun. 2018, 39, 1700737. (7) Zanchet, D.; Micheel, C. M.; Parak, W. J.; Gerion, D.; Alivisatos, A. P. Electrophoretic Isolation of Discrete Au Nanocrystal/DNA Conjugates. Nano Lett. 2001, 1, 32−35. (8) Mavila, S.; Eivgi, O.; Berkovich, I.; Lemcoff, N. G. Intramolecular Cross-Linking Methodologies for the Synthesis of Polymer Nanoparticles. Chem. Rev. 2016, 116, 878−961. (9) Njikang, G.; Liu, G.; Curda, S. A. Tadpoles from the Intramolecular Photo-Cross-Linking of Diblock Copolymers. Macromolecules 2008, 41, 5697−5702. (10) Wu, H.; Yang, H. K.; Wang, W. Covalently-Linked Polyoxometalate-Polymer Hybrids: Optimizing Synthesis, Appealing Structures and Prospective Applications. New J. Chem. 2016, 40, 886− 897. (11) Yu, X.; Yue, K.; Hsieh, I. F.; Li, Y.; Dong, X. H.; Liu, C.; Xin, Y.; Wang, H. F.; Shi, A. C.; Newkome, G. R.; Ho, R. M.; Chen, E. Q.; Zhang, W. B.; Cheng, S. Z. D. Giant Surfactants Provide a Versatile Platform for Sub-10-nm Nanostructure Engineering. Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 10078−10083. (12) Han, Y.; Xiao, Y.; Zhang, Z.; Liu, B.; Zheng, P.; He, S.; Wang, W. Synthesis of Polyoxometalate−Polymer Hybrid Polymers and Their Hybrid Vesicular Assembly. Macromolecules 2009, 42, 6543− 6548. (13) Zhang, W.; Fang, B.; Walther, A.; Müller, A. H. E. Synthesis via RAFT Polymerization of Tadpole-Shaped Organic/Inorganic Hybrid Poly(acrylic acid) Containing Polyhedral Oligomeric Silsesquioxane (POSS) and Their Self-assembly in Water. Macromolecules 2009, 42, 2563−2569. (14) Zhang, W. B.; Yu, X.; Wang, C. L.; Sun, H. J.; Hsieh, I. F.; Li, Y.; Dong, X. H.; Yue, K.; Van Horn, R.; Cheng, S. Z. D. Molecular Nanoparticles Are Unique Elements for Macromolecular Science: From “Nanoatoms” to Giant Molecules. Macromolecules 2014, 47, 1221−1239. (15) Hu, J.; Wu, T.; Zhang, G.; Liu, S. Efficient Synthesis of Single Gold Nanoparticle Hybrid Amphiphilic Triblock Copolymers and Their Controlled Self-Assembly. J. Am. Chem. Soc. 2012, 134, 7624− 7627. (16) Worden, J. G.; Shaffer, A. W.; Huo, Q. Controlled Functionalization of Gold Nanoparticles through a Solid Phase Synthesis Approach. Chem. Commun. 2004, 518−519. (17) Yao, X.; Jing, J.; Liang, F.; Yang, Z. Polymer-Fe3O4 Composite Janus Nanoparticles. Macromolecules 2016, 49, 9618−9625. (18) Jing, J.; Yao, X.; Yang, Z. Single Polymer Chain Grafted Fe3O4 Composite Janus Nanoparticle. Acta Polym. Sin. 2018, 1066−1072. (19) Geng, Y.; Dalhaimer, P.; Cai, S.; Tsai, R.; Tewari, M.; Minko, T.; Discher, D. E. Shape Effects of Filaments versus Spherical Particles in Flow and Drug Delivery. Nat. Nanotechnol. 2007, 2, 249−255. (20) Johnson, J. A.; Lu, Y. Y.; Burts, A. O.; Xia, Y.; Durrell, A. C.; Tirrell, D. A.; Grubbs, R. H. Drug-Loaded, Bivalent-Bottle-Brush Polymers by Graft-through ROMP. Macromolecules 2010, 43, 10326− 10335. (21) Verduzco, R.; Li, X.; Pesek, S. L.; Stein, G. E. Structure, Function, Self-Assembly, and Applications of Bottlebrush Copolymers. Chem. Soc. Rev. 2015, 44, 2405−2420. (22) Xie, G.; Martinez, M. R.; Olszewski, M.; Sheiko, S. S.; Matyjaszewski, K. Molecular Bottlebrushes as Novel Materials. Biomacromolecules 2019, 20, 27−54. (23) Müllner, M.; Dodds, S. J.; Nguyen, T.-H.; Senyschyn, D.; Porter, C. J. H.; Boyd, B. J.; Caruso, F. Size and Rigidity of Cylindrical Polymer Brushes Dictate Long Circulating Properties In Vivo. ACS Nano 2015, 9, 1294−1304. (24) Li, H.; Liu, H.; Nie, T.; Chen, Y.; Wang, Z.; Huang, H.; Liu, L.; Chen, Y. Molecular Bottlebrush as a Unimolecular Vehicle with Tunable Shape for Photothermal Cancer Therapy. Biomaterials 2018, 178, 620−629.

the whole hydrogel is dyed green (Figure 4d). In contrast, the aggregates are spherical in the voids at pH 8 (Figure 4e). No release of the dyed toluene is observed after a long time (e.g., 12 h) (Figure 4f). Starting from the single PVBC-chain-grafted Fe3O4 JNPs, bottlebrush-colloid JNPs were derived by sequential ATRP of DEAEMA and OEGMA from the PVBC backbone. The JNPs demonstrate a ball-and-stick structure in TEM observations. The amine-group-capped Fe3O4 colloidal ball is responsible for target recognition and magnetic guidance. The stick formed by the PDEAEMA-b-POEGMA core/shell bottlebrush is responsible for the pH-triggered controlled release. The pH-triggered release of the hydrophobic species under the magnetic guidance was demonstrated. Interestingly, the pH-responsive window lies within the pH range found in solid tumors. More precise and selective targeting is expected by conjugating biological ligands onto the amine-capped surface of the JNPs. The JNPs are promising as a new pH-triggered drug delivery vector toward tumors that can be guided by the application of a magnetic field.

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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/acsmacrolett.9b00234.

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XRD, TGA traces, VSM curves, TEM and SEM images, DLS traces, FT-IR spectra, NMR spectra, and experimental procedures (PDF)

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (Z.Y.). *E-mail: [email protected] (B.J.). ORCID

Bingyin Jiang: 0000-0002-9526-5727 Zhenzhong Yang: 0000-0002-4810-7371 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China (Z.Y.: 51833005, B.J.: 51703229, and F.L.: 51622308). We sincerely thank Dr. Xiaoli Zhang from ICCAS for her help to perform the GPC tests. We also appreciate Ms. Jiling Yue and Dr. Bo Guan for their kind help on the TEM and SEM sample preparation.

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REFERENCES

(1) De Gennes, P. G. Soft Matter. Science 1992, 256, 495−497. (2) Gröschel, A. H.; Walther, A.; Löbling, T. I.; Schacher, F. H.; Schmalz, H.; Müller, A. H. E. Guided Hierarchical Co-Assembly of Soft Patchy Nanoparticles. Nature 2013, 503, 247−251. (3) Wen, J.; Yuan, L.; Yang, Y.; Liu, L.; Zhao, H. Self-Assembly of Monotethered Single-Chain Nanoparticle Shape Amphiphiles. ACS Macro Lett. 2013, 2, 100−106. (4) Yu, X.; Zhang, W. B.; Yue, K.; Li, X.; Liu, H.; Xin, Y.; Wang, C. L.; Wesdemiotis, C.; Cheng, S. Z. D. Giant Molecular Shape Amphiphiles Based on Polystyrene−Hydrophilic [60]Fullerene Conjugates: Click Synthesis, Solution Self-Assembly, and Phase Behavior. J. Am. Chem. Soc. 2012, 134, 7780−7787. 741

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ACS Macro Letters (25) Sun, S.; Zeng, H. Size-Controlled Synthesis of Magnetite Nanoparticles. J. Am. Chem. Soc. 2002, 124, 8204−8205. (26) De Palma, R.; Peeters, S.; Van Bael, M. J.; Van den Rul, H.; Bonroy, K.; Laureyn, W.; Mullens, J.; Borghs, G.; Maes, G. Silane Ligand Exchange to Make Hydrophobic Superparamagnetic Nanoparticles Water-Dispersible. Chem. Mater. 2007, 19, 1821−1831. (27) Nakagawa, Y.; Miller, P. J.; Matyjaszewski, K. Development of Novel Attachable Initiators for Atom Transfer Radical Polymerization. Synthesis of Block and Graft Copolymers from Poly(dimethylsiloxane) Macroinitiators. Polymer 1998, 39, 5163−5170. (28) Fischer, K.; Hoffmann, P.; Voelkl, S.; Meidenbauer, N.; Ammer, J.; Edinger, M.; Gottfried, E.; Schwarz, S.; Rothe, G.; Hoves, S.; Renner, K.; Timischl, B.; Mackensen, A.; Kunz-Schughart, L.; Andreesen, R.; Krause, S. W.; Kreutz, M. Inhibitory Effect of Tumor Cell−Derived Lactic Acid on Human T Cells. Blood 2007, 109, 3812−3819.

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