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Letter Cite This: J. Phys. Chem. Lett. 2019, 10, 4185−4191

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Near-Infrared Light-Triggered Porous AuPd Alloy Nanoparticles To Produce Mild Localized Heat To Accelerate Bone Regeneration Xingang Zhang,†,# Gu Cheng,‡,# Xin Xing,‡ Jiangchao Liu,† Yuet Cheng,‡ Tianyu Ye,† Qun Wang,∥ Xiangheng Xiao,*,† Zubing Li,*,‡ and Hongbing Deng*,§

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Department of Physics and Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, Hubei Nuclear Solid Physics Key Laboratory and Center for Ion Beam Application, Wuhan University, Wuhan 430072, China ‡ State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education & Department of Oral and Maxillofical Trauma and Plastic Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China § School of Resource and Environmental Science and Hubei Biomass-Resource Chemistry and Environmental Biotechnology Key Laboratory, Wuhan University, Wuhan 430079, P. R. China ∥ Department of Chemical and Biological Engineering, Iowa State University, Ames, Iowa 50011, United States S Supporting Information *

ABSTRACT: The treatment of massive bone defects is still a significant challenge for orthopedists. Here we have engineered synthetic porous AuPd alloy nanoparticles (pAuPds) as a hyperthermia agent for in situ bone regeneration through photothermal therapy (PTT). After being swallowed by cells, pAuPds produced a mild localized heat (MLH) (40−43 °C) under the irradiation of a nearinfrared laser, which can greatly accelerate cell proliferation and bone regeneration. Almost 97% of the cranial defect area (8 mm in diameter) was covered by the newly formed bone after 6 weeks of PTT. RNA sequencing analysis was used to obtain insight into the molecular mechanism of the MLH on cell proliferation and bone formation. These results demonstrated that the Wnt signaling pathway was involved in the MLH. This Letter provides a unique strategy with mild heat stimulation and high efficiency for in situ bone regeneration.

T

phonon and the medium. Finally, heat diffuses in the medium. When NIR photothermal agents are released in the tumor or eye disease area and irradiated by NIR light, the high temperature produced (>46 °C) can effectively kill tumor cells21 or lens epithelial cells.31 These treatment strategies are based on the threshold temperature (46 °C) required for hyperthermia-mediated destruction of cells.33 However, there is little literature on the effect of low temperature (40−43 °C) on cells. Because of the good biocompatibility and tunable localized surface plasmon resonance (LSPR) absorption band, Au nanostructures are considered as one of the best candidate materials for PTT.34 However, the LSPR absorption band of Au nanoparticles often locates at 450−520 nm, which is outside of the NIR region.35,36 Regulating the morphology and introducing another metal are two of the most effective strategies for adjusting the absorption band.37−39 Palladium (Pd) also has good biocompatibility, which is considered as a logical choice to preserve the nontoxic properties of Au

he treatment of large-size bone defects remains a formidable problem for orthopedic surgeons.1−6 Autologous and allogeneic bone grafts are the two main treatment options for bone defects;7−12 however, both options demonstrate a considerable risk to patients, such as significant pain, fracture, nonunion, and infection.13,14 In addition, growth factors are also utilized in the treatment of bone defects.15−19 However, for bone defects caused by the surgical removal of carcinomas, growth factors are avoided due to their possible interaction with residual cancer cells.20 Therefore, the development of a high-efficacy, universal approach with low adverse effects for in situ bone regeneration is urgently needed. Photothermal therapy (PTT) has recently been widely used in various diseases.21−31 Owing to the superior tissuepenetration ability and low energy loss of near-infrared (NIR) light, NIR photothermal agents can effectively convert absorbed NIR light into heat. The process of heat generation is as follows:32 First, nascent nonthermal electrons are created when the electronic system absorbs the laser light. Along with the scattering between electrons, a thermal equilibrium is achieved. Then, through the coupling between electrons and phonons, the energy of electrons is transferred to the lattice of nanoparticles. Subsequently, the surrounding medium gets energy from the lattice through the interaction between the © XXXX American Chemical Society

Received: June 15, 2019 Accepted: July 12, 2019 Published: July 12, 2019 4185

DOI: 10.1021/acs.jpclett.9b01735 J. Phys. Chem. Lett. 2019, 10, 4185−4191

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The Journal of Physical Chemistry Letters nanomaterials.40,41 Therefore, the synthesis of AuPd alloy composition with NIR absorption is highly suited for PTT. Herein we synthesized porous AuPd alloy nanoparticles (pAuPds) with the absorption band of 705 nm and explored them as NIR photothermal agents to produce mild localized heat (MLH) (40−43 °C) under the NIR laser irradiation for rapid in situ bone regeneration in vivo (Figure 1). Both in vitro

The pAuPds were prepared through a convenient and effective wet-chemical strategy. (See the Supporting Information.)42 Transmission electron microscopy (TEM) images of pAuPds synthesized by adding different molar ratios between Pd and Au are shown in Figure 2 and Figure S1. It could be seen that only when the molar ratio between Pd and Au was 2:2 could the uniform nanostructures with nearly spherical profiles containing a solid core and densely branched shells be obtained (Figure 2a). The elemental mapping of pAuPds obtained by HAADF-STEM-EDS revealed that Au was in the core, whereas Pd homogeneously distributed throughout the whole shell (Figure 2b). The X-ray diffraction (XRD) pattern showed that all of the diffraction peaks belong to the fcc structures of Au and Pd (Figure S2).42 The result confirms the existence of metallic Au and Pd. In this synthesis, the reducing agent played the key factor. If ascorbic acid was replaced with ascorbic acid sodium salt, phloroglucinol, citric acid, sodium citrate, or glucose, then only lower quality pAuPds or other irregularly shaped nanostructures instead of pAuPds formed (Figure S3−S7). This means that the formation of uniform pAuPds needs a moderate reducing power to control the growth rate, and a stronger or weaker reducing power would affect the formation of uniform porous structures.42 The UV−visible spectroscopy of pAuPds was shown in Figure 2c. The absorption peak appeared at 705 nm, and strong absorption also appeared at 808 nm which is within the 650−900 nm NIR window, suggesting the potential for PTT applications. To further demonstrate that pAuPds are a potential and suitable NIR PTT agent, we investigated the photothermal effect. An 808 nm laser (2 W cm−2) was used to irradiate 0.5

Figure 1. Schematic illustration of pAuPds for PTT of cranial defect.

and in vivo experiments showed that MLH could effectively promote cell proliferation and bone regeneration. The mechanism of cell proliferation and bone healing has been carefully examined. Notably, pAuPds show weak toxicity for cells and organs. This study opens a new avenue for highly efficient bone defect treatment.

Figure 2. Characterizations of pAuPds under the molar ratios between Pd and Au is 2:2. (a) TEM image, (b) elemental analysis, (c) UV−visible spectra, (d) temperature measurements of pAuPds under laser irradiation, and (e) relative viability of preosteoblast-MC3T3-E1 cells after incubation with different concentrations pAuPds. (f) Comparison of preosteoblast-MC3T3-E1 cells viability at different experimental treatments (pAuPds: 50 μg mL−1). 4186

DOI: 10.1021/acs.jpclett.9b01735 J. Phys. Chem. Lett. 2019, 10, 4185−4191

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The Journal of Physical Chemistry Letters

Figure 3. (a) Optical image of the rat critical-sized cranial defect. (b) Micro-CT images of cranial defect after 3 and 6 weeks of PTT. (c) Quantitative analysis of the newly formed bone in different groups; bone coverage (%) = newly formed bone area (S)/the original defect area (S). (d) Histological evaluation of bone formation at 3 and 6 weeks.

difference in cell proliferation was still very small, whereas the cell proliferation in group 3 was 1.22 times as high as that in group 1, and group 4 was 1.7 times as high as that in group 1. Moreover, after 48 h of incubation, the cell proliferation in groups 1 and 2 remained the same; however, the cell proliferation in groups 3 and 4 was still 1.1 and 1.6 times as high as that in group 1, respectively. Different cell proliferation rates were attributed to different temperature treatments. For groups 1 and 2, cells were cultured at room temperature during the entire period and always maintained a normal rate of cell proliferation. For group 3, owing to laser irradiation, there was a slight increase in the temperature of the culture medium, which accelerated the cell proliferation rate, but not very obviously. For group 4, NIR light was absorbed by pAuPds and produced an appropriate temperature (40−43 °C), which greatly promoted the cell proliferation. These results demonstrated that MLH can greatly accelerate cell proliferation and has the potential for rapid bone regeneration. Inspired by the exciting results in vitro, we further carried out animal experiments to test PTT in vivo. After the fullthickness defects (8 mm in diameter) were created on both sides of the cranial bone (Figure 3a), 36 defects were randomly divided into three groups: (1) PBS (100 μL) as the negative control group (NCG), (2) PBS (100 μL) + laser irradiation as the positive control group (PCG), and (3) pAuPds (0.08 mg Au kg−1, 100 μL) + laser irradiation as the experimental group (EG). To have a high enough particle concentration in the defect area, 100 μL of PBS or pAuPds solution was directly injected into the space between the surface of the cranial defects and the skin. At 0.5 h postinjection, rats in NCG and EG were anaesthetized, an 808 nm laser (2 W cm−2) was used to irradiate the entire region of the defect, and an infrared thermal imaging camera was used to monitor the temperature of the defect region (Figure S9). After irradiation for 3 min, the

mL of a PBS solution containing different concentrations of pAuPds for 5 min; simultaneously, the temperature was monitored. As shown in Figure 2d, PBS containing pAuPds exhibited a rapid temperature response; even though the concentration was as low as 50 μg mL−1, the temperature of the solution could still rapidly reach ∼43 °C within 3 min. In contrast, the PBS control showed only a slightly increase, indicating that pAuPds could be used for highly efficient PTT. To evaluate the possible cytotoxicity of pAuPds, preosteoblast-MC3T3-E1 cells were incubated with pAuPds at different Au concentrations (0, 25, 50, 100, and 200 μg mL−1) for 48 h. As shown in Figure 2e, there was no obvious cytotoxicity of pAuPds, even with a concentration as high as 200 μg mL−1, which indicated a potential biosafety of this material. Moreover, preosteoblast-MC3T3-E1 cells cocultured with pAuPds were observed by the optical dark field (Figure S8). Compared with cells without pAuPds, there were some bright clusters (as indicated by the red arrow) inside the cells cocultured with pAuPds (50 μg mL−1). When the concentration of pAuPds increased (100 μg mL−1), more bright clusters appeared. These bright clusters were attributed to the scattering of pAuPds, suggesting that pAuPds entered into cells. After confirming the good biocompatibility of pAuPds, we explored the effects of MLH on cells (Figure 2f). Twenty wells containing preosteoblast-MC3T3-E1 cells were randomly divided into four groups: group 1, only added PBS; group 2, PBS + pAuPds; group 3, PBS + laser irradiation; group 4, PBS + pAuPds + laser irradiation. The detailed procedure is shown in the Supporting Information and the Supplementary Video. CCK-8 was used to analyze the cell proliferation after 12, 24, and 48 h of incubation. As shown in Figure 2f, cell proliferation among these four groups almost the same after 12 h. However, the difference increased after 24 h: For groups 1 and 2, the 4187

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Figure 4. Gene expression profiles between NP+L (experimental group) and C (control group) groups. (a) Heatmap for global gene expression. (b) Volcano map and (c) gene ontology enrichment of differentially expressed genes. (d) Western blot of Hsp47 and BMP2 in MC3T3-E1 cells treated with different methods for 8 days.

(40−43 °C) produced in the EG can greatly promote cell proliferation (Figure 2f). To further evaluate the effect of PTT on bone regeneration, harvested cranial samples were analyzed histologically (Figure 3d), which showed that the rats in the EG exhibited an intramembranous bone formation. Two ends of the tibial fracture had been bridged by the newly formed bone tissue, and the defect area had almost remolded to its original shape after 6 weeks of healing. In comparison, the PCG showed moderate newly formed bone, whereas the NCG exhibited the lowest newly formed bone in the defect area. These results demonstrate that MLH can rapidly promote in vivo bone regeneration. Furthermore, we evaluated BrdU (cell proliferation marker) and osteocalcin (the late osteogenic differentiation marker)43 in the defect areas (Figure S10a,b). At 3 weeks after surgery, the expression of BrDU and osteocalcin (as indicated by the red arrow) was very low in EG but still a little higher than in the other group. After 6 weeks, the expression of BrDU and osteocalcin in EG was very obvious and far higher than those in PCG and NCG, which was confirmed by the results of in vitro studies. These results demonstrated that the cell proliferation in the defect sites almost ceased, but MLH could restart and enhance the cell proliferation. Moreover, the high expression of osteocalcin in EG corresponded to the

temperature of the defect in the PCG increased from 36.2 to 38.5 °C, whereas the temperature in EG increased from 35.7 to 43 °C. To prevent the high temperature (>46 °C) from damaging the viability of cells,33 the laser was turned off to bring the temperature of the defect down to body temperature after irradiation for 3 min, and then the second 3 min of irradiation was carried out; this process was repeated 10 times. These results indicated the high efficiency of pAuPds as a photothermal agent in vivo. To assess the bone regeneration capability, rats received PTT every 5 days. After 3 and 6 weeks of surgery, cranial defects were investigated by microcomputed tomography (micro-CT) reconstruction (Figure 3b). At 3 weeks after surgery, the cranial defects in the NCG showed the slowest healing rate, with 21% newly formed bone coverage. In contrast, ∼29% of defect areas were covered with new bone in the PCG, whereas >79% were covered in the EG. After 6 weeks, in the NCG, only a little new bone formation (22%) was observed, whereas bone formation was 72% in the PCG and 97% in the EG (Figure 3b,c). Different bone regeneration capabilities can be attributed to two factors. First, bone lesions above a critical size have difficultly healing themselves without any outside stimulus.5 Second, compared with the lowtemperature rise (from 36.2 to 38.5 °C) in the PCG, MLH 4188

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The Journal of Physical Chemistry Letters results of the study of the following mechanism, in which the activation of the Wnt signaling pathway by MLH resulted in the expression of osteocalcin.44 The in vivo toxicology of pAuPds was investigated. In this work, the histological changes of organs were checked by collecting the major organs, including the heart, liver, spleen, lung, and kidney, and slicing them for hematoxylin and eosin (H&E) staining (Figure S10c). No significant organ damage was observed from control and experimental groups, which further indicates the superior biocompatibility of the pAuPds in vivo. To obtain insight into the molecular mechanism of MLH on cell proliferation and bone formation, RNA sequencing (RNAseq) analysis was performed to detect differentially expressed genes in MC3T3-E1 cells treated under different conditions (Figure 4a−c). RNA-seq analysis showed that compared with the cells in the control group (neither pAuPds nor laser irradiation), there were 363 screened genes with 132 upregulated and 231 down-regulated in cells treated with pAuPds and laser irradiation (experimental group); furthermore, a great difference was observed in the gene expression between the experimental and control groups (Figure 4a). These results of gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses demonstrated that MLH upregulated the expression of Wnt10b, A1p1, and Hspb1 genes (Figure 4b). Previous studies demonstrated that Wnt10b and A1p1 genes enhanced the osteoblastic differentiation of mesenchymal stem cells through Wnt signaling pathway.45 These results demonstrated that the Wnt signaling pathway might be involved in MLH (Figure 4c). To further verify the possible mechanisms, the expression of heat shock protein 47 (Hsp47) and bone morphogenetic protein 2 (BMP2) was studied by Western blot (Figure 4d). Hsp47 has been proved to be essential in well-organized cartilage and the normal formation of endochondral bone,46 whereas BMP2 is a main regulator for the Wnt signaling pathway,47 and the local high expression of BMP2 in the site of bone injury resulted in increased healing rates.48 Moreover, stromal differentiation that was induced by BMP2 was prohibited by the attenuation of small interfering RNAirradiated WNT4 expression.49 In this study, cells treated with pAuPds and laser irradiation showed the largest expression level of Hsp47 and BMP2 among these four groups. These results were conformed to RNA-seq analysis and demonstrated that MLH could greatly promote the expression of Hsp47 and BMP2. Simultaneously, BMP2 induced by the MLH might activate the Wnt signaling pathway and promote bone regeneration. In summary, we have demonstrated the use of pAuPds as an effective hyperthermia agent for photothermal bone defect therapy. Both in vitro and in vivo experiments showed that MLH can efficiently promote cell proliferation and bone regeneration. The mechanism of bone healing was carefully studied. This report provides a unique strategy with low cytotoxicity and high efficiency for in situ bone regeneration therapy.

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Experimental details and additional figures showing TEM images, optical dark field images, infrared thermographic maps, and immunostaining (PDF) Supplementary Video 1. After irradiation for 3 min, the laser is turned off to bring the temperature of the cells down to normal to avoid damaging cells (AVI)

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (X.X.). *E-mail: [email protected] (Z.L.). *E-mail: [email protected] (H.D.) ORCID

Qun Wang: 0000-0002-5660-5602 Xiangheng Xiao: 0000-0001-9111-1619 Zubing Li: 0000-0002-3499-7684 Hongbing Deng: 0000-0002-9784-6138 Author Contributions #

X.Z. and G.C. contributed equally to this work.

Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We acknowledge the NSFC (11722543, U1867215, 81800943), the Fundamental Research Funds for the Central Universities (2042019kf0312), and Suzhou Key Industrial Technology Innovation Project (SYG201828).

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REFERENCES

(1) van Griensven, M. Preclinical testing of drug delivery systems to bone. Adv. Drug Delivery Rev. 2015, 94, 151−164. (2) Agarwal, R.; Garcia, A. J. Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair. Adv. Drug Delivery Rev. 2015, 94, 53−62. (3) Taylor, D.; Hazenberg, J. G.; Lee, T. C. Living with cracks: damage and repair in human bone. Nat. Mater. 2007, 6, 263. (4) Khosla, S.; Westendorf, J. J.; Oursler, M. J. Building bone to reverse osteoporosis and repair fractures. J. Clin. Invest. 2008, 118, 421−428. (5) Petite, H.; Viateau, V.; Bensaïd, W.; Meunier, A.; de Pollak, C.; Bourguignon, M.; Oudina, K.; Sedel, L.; Guillemin, G. Tissueengineered bone regeneration. Nat. Biotechnol. 2000, 18, 959. (6) Stevens, M. M. Biomaterials for bone tissue engineering. Mater. Today 2008, 11, 18−25. (7) Lutolf, M. P.; Weber, F. E.; Schmoekel, H. G.; Schense, J. C.; Kohler, T.; Muller, R.; Hubbell, J. A. Repair of bone defects using synthetic mimetics of collagenous extracellular matrices. Nat. Biotechnol. 2003, 21, 513−518. (8) Mandal, B. B.; Grinberg, A.; Seok Gil, E. S.; Panilaitis, B.; Kaplan, D. L. High-strength silk protein scaffolds for bone repair. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 7699−7704. (9) Lee, S. H.; Shin, H. Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering. Adv. Drug Delivery Rev. 2007, 59, 339−359. (10) Kolambkar, Y. M.; Dupont, K. M.; Boerckel, J. D.; Huebsch, N.; Mooney, D. J.; Hutmacher, D. W.; Guldberg, R. E. An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects. Biomaterials 2011, 32, 65−74. (11) Fu, Q.; Saiz, E.; Rahaman, M. N.; Tomsia, A. P. Toward strong and tough glass and ceramic scaffolds for bone repair. Adv. Funct. Mater. 2013, 23, 5461−5476. (12) Cancedda, R.; Giannoni, P.; Mastrogiacomo, M. A tissue engineering approach to bone repair in large animal models and in clinical practice. Biomaterials 2007, 28, 4240−4250.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jpclett.9b01735. 4189

DOI: 10.1021/acs.jpclett.9b01735 J. Phys. Chem. Lett. 2019, 10, 4185−4191

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The Journal of Physical Chemistry Letters (13) Mankin, H. J.; Hornicek, F. J.; Raskin, K. A. Infection in massive bone allografts. Clin. Orthop. Relat. Res. 2005, 210−216. (14) Schwartz, C. E.; Martha, J. F.; Kowalski, P.; Wang, D. A.; Bode, R.; Li, L.; Kim, D. H. Prospective evaluation of chronic pain associated with posterior autologous iliac crest bone graft harvest and its effect on postoperative outcome. Health. Qual. Life. Out. 2009, 7, 49. (15) Vo, T. N.; Kasper, F. K.; Mikos, A. G. Strategies for controlled delivery of growth factors and cells for bone regeneration. Adv. Drug Delivery Rev. 2012, 64, 1292−1309. (16) Chen, R.; Wang, J.; Liu, C. S. Biomaterials act as enhancers of growth factors in bone regeneration. Adv. Funct. Mater. 2016, 26, 8810−8823. (17) Street, J.; Bao, M.; deGuzman, L.; Bunting, S.; Peale, F. V.; Ferrara, N.; Steinmetz, H.; Hoeffel, J.; Cleland, J. L.; Daugherty, A.; van Bruggen, N.; Redmond, H. P.; Carano, R. A. D.; Filvaroff, E. H. Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 9656−9661. (18) Shekaran, A.; Garcia, J. R.; Clark, A. Y.; Kavanaugh, T. E.; Lin, A. S.; Guldberg, R. E.; Garcia, A. J. Bone regeneration using an alpha 2 beta 1 integrin-specific hydrogel as a BMP-2 delivery vehicle. Biomaterials 2014, 35, 5453−5461. (19) Zhou, J.; Lin, H.; Fang, T.; Li, X.; Dai, W.; Uemura, T.; Dong, J. The repair of large segmental bone defects in the rabbit with vascularized tissue engineered bone. Biomaterials 2010, 31, 1171− 1179. (20) Heo, D. N.; Ko, W. K.; Bae, M. S.; Lee, J. B.; Lee, D. W.; Byun, W.; Lee, C. H.; Kim, E. C.; Jung, B. Y.; Kwon, I. K. Enhanced bone regeneration with a gold nanoparticle−hydrogel complex. J. Mater. Chem. B 2014, 2, 1584−1593. (21) Shao, J.; Xie, H.; Huang, H.; Li, Z.; Sun, Z.; Xu, Y.; Xiao, Q.; Yu, X. F.; Zhao, Y.; Zhang, H.; Wang, H.; Chu, P. K. iodegradable black phosphorus-based nanospheres for in vivo photothermal cancer therapy. Nat. Commun. 2016, 7, 12967. (22) Ali, M. R. K.; Rahman, M. A.; Wu, Y.; Han, T. G.; Peng, X. H.; Mackey, M. A.; Wang, D. S.; Shin, H. J.; Chen, Z. G.; Xiao, H. P.; Wu, R. H.; Tang, Y.; Shin, D. M.; El-Sayed, M. A. Efficacy, long-term toxicity, and mechanistic studies of gold nanorods photothermal therapy of cancer in xenograft mice. Proc. Natl. Acad. Sci. U. S. A. 2017, 114, E3110−E3118. (23) Lin, H.; Gao, S.; Dai, C.; Chen, Y.; Shi, J. A two-dimensional biodegradable niobium carbide (MXene) for photothermal tumor eradication in NIR-I and NIR-II biowindows. J. Am. Chem. Soc. 2017, 139, 16235−16247. (24) Lee, C.; Hwang, H. S.; Lee, S.; Kim, B.; Kim, J. O.; Oh, K. T.; Lee, E. S.; Choi, H. G.; Youn, Y. S. Rabies virus-inspired silica-coated gold nanorods as a photothermal therapeutic platform for treating brain tumors. Adv. Mater. 2017, 29, 1605563. (25) Chu, C.; Lin, H.; Liu, H.; Wang, X.; Wang, J.; Zhang, P.; Gao, H.; Huang, C.; Zeng, Y.; Tan, Y.; Liu, G.; Chen, X. Tumor Microenvironment-Triggered Supramolecular System as an In Situ Nanotheranostic Generator for Cancer Phototherapy. Adv. Mater. 2017, 29, 1605928. (26) Chen, W.; Ouyang, J.; Liu, H.; Chen, M.; Zeng, K.; Sheng, J.; Liu, Z.; Han, Y.; Wang, L.; Li, J.; Deng, L.; Liu, Y. N.; Guo, S. Black Phosphorus Nanosheet-Based Drug Delivery System for Synergistic Photodynamic/Photothermal/Chemotherapy of Cancer. Adv. Mater. 2017, 29, 1603864. (27) Chen, Y. W.; Su, Y. L.; Hu, S. H.; Chen, S. Y. Functionalized graphene nanocomposites for enhancing photothermal therapy in tumor treatment. Adv. Drug Delivery Rev. 2016, 105, 190−204. (28) Liu, Y.; Wang, Z.; Liu, Y.; Zhu, G.; Jacobson, O.; Fu, X.; Bai, R.; Lin, X.; Lu, N.; Yang, X.; Fan, W.; Song, J.; Wang, Z.; Yu, G.; Zhang, F.; Kalish, H.; Niu, G.; Nie, Z.; Chen, X. Suppressing nanoparticlemononuclear phagocyte system interactions of two-dimensional gold nanorings for improved tumor accumulation and photothermal ablation of tumors. ACS Nano 2017, 11, 10539−10548.

(29) Yang, B. W.; Chen, Y.; Shi, J. L. Material chemistry of twodimensional inorganic nanosheets in cancer theranostics. Chem. 2018, 4, 1284−1313. (30) He, W.; Frueh, J.; Hu, N.; Liu, L.; Gai, M.; He, Q. Guidable thermophoretic Janus micromotors containing gold nanocolorifiers for infrared laser assisted tissue welding. Adv. Sci. 2016, 3, 1600206. (31) Lin, Y. X.; Hu, X. F.; Zhao, Y.; Gao, Y. J.; Yang, C.; Qiao, S. L.; Wang, Y.; Yang, P. P.; Yan, J.; Sui, X. C.; Qiao, Z. Y.; Li, L. L.; Xie, J. B.; Zhu, S. Q.; Wu, X. C.; Li, Y.; Wang, L.; Wang, H. Photothermal ring integrated intraocular lens for high-efficient eye disease treatment. Adv. Mater. 2017, 29, 1701617. (32) Hashimoto, S.; Werner, D.; Uwada, T. Studies on the interaction of pulsed lasers with plasmonic gold nanoparticles toward light manipulation, heat management, and nanofabrication. J. Photochem. Photobiol., C 2012, 13, 28−54. (33) McGrath, A. J.; Chien, Y. H.; Cheong, S.; Herman, D. A.; Watt, J.; Henning, A. M.; Gloag, L.; Yeh, C. S.; Tilley, R. D. Gold over branched palladium nanostructures for photothermal cancer therapy. ACS Nano 2015, 9, 12283−12291. (34) Cheng, X.; Sun, R.; Yin, L.; Chai, Z.; Shi, H.; Gao, M. LightTriggered Assembly of Gold Nanoparticles for Photothermal Therapy and Photoacoustic Imaging of Tumors In Vivo. Adv. Mater. 2017, 29, 1604894. (35) Daniel, M. C.; Astruc, D. Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. Chem. Rev. 2004, 104, 293−346. (36) Zhang, X. G.; Dai, Z. G.; Si, S. Y.; Zhang, X. L.; Wu, W.; Deng, H. B.; Wang, F. B.; Xiao, X. H.; Jiang, C. Z. Ultrasensitive SERS substrate integrated with uniform subnanometer scale “hot spots” created by a graphene spacer for the detection of mercury ions. Small 2017, 13, 1603347. (37) Chen, J. Y.; Wang, D. L.; Xi, J. F.; Au, L.; Siekkinen, A.; Warsen, A.; Li, Z. Y.; Zhang, H.; Xia, Y. N.; Li, X. Immuno gold nanocages with tailored optical properties for targeted photothermal destruction of cancer cells. Nano Lett. 2007, 7, 1318−1322. (38) Espinosa, A.; Curcio, A.; Cabana, S.; Radtke, G.; Bugnet, M.; Kolosnjaj-Tabi, J.; Pechoux, C.; Alvarez-Lorenzo, C.; Botton, G. A.; Silva, A. K. A.; Abou-Hassan, A.; Wilhelm, C. Intracellular Biodegradation of Ag Nanoparticles, Storage in Ferritin, and Protection by a Au Shell for Enhanced Photothermal Therapy. ACS Nano 2018, 12, 6523−6535. (39) Song, L. Z.; Zhou, X.; Dai, X. G.; Wang, R.; Cheng, G.; Zhao, N. N.; Xu, F. J. Self-destructible polysaccharide nanocomposites with unlockable Au nanorods for high-performance photothermal therapy. NPG Asia Mater. 2018, 10, 509−521. (40) Long, R.; Mao, K.; Ye, X.; Yan, W.; Huang, Y.; Wang, J.; Fu, Y.; Wang, X.; Wu, X.; Xie, Y.; Xiong, Y. Surface facet of palladium nanocrystals: A key parameter to the activation of molecular oxygen for organic catalysis and cancer treatment. J. Am. Chem. Soc. 2013, 135, 3200−3207. (41) Huang, X. Q.; Tang, S. H.; Mu, X. L.; Dai, Y.; Chen, G. X.; Zhou, Z. Y.; Ruan, F. X.; Yang, Z. L.; Zheng, N. F. Freestanding palladium nanosheets with plasmonic and catalytic properties. Nat. Nanotechnol. 2011, 6, 28−32. (42) Huang, X. Q.; Li, Y. J.; Chen, Y.; Zhou, E. B.; Xu, Y. X.; Zhou, H. L.; Duan, X. F.; Huang, Y. Palladium-based nanostructures with highly porous features and perpendicular pore channels as enhanced organic catalysts. Angew. Chem. 2013, 125, 2580−2584. (43) Nakashima, K.; Zhou, X.; Kunkel, G.; Zhang, Z. P.; Deng, J. M.; Behringer, R. R.; de Crombrugghe, B. The novel zinc fingercontaining transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 2002, 108, 17−29. (44) Chen, X. j.; Shen, Y. S.; He, M. C.; Yang, F.; Yang, P.; Pang, F. X.; He, W.; Cao, Y. M.; Wei, Q. S. Polydatin promotes the osteogenic differentiation of human bone mesenchymal stem cells by activating the BMP2-Wnt/β-catenin signaling pathway. Biomed. Pharmacother. 2019, 112, 108746. 4190

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Letter

The Journal of Physical Chemistry Letters (45) Huang, X.; Zhong, L.; Hendriks, J.; Post, J.; Karperien, M. The effects of the WNT-signaling modulators BIO and PKF118−310 on the chondrogenic differentiation of human mesenchymal stem cells. Int. J. Mol. Sci. 2018, 19, 561. (46) Ito, S.; Nagata, K. Roles of the endoplasmic reticulum− resident, collagen-specific molecular chaperone Hsp47 in vertebrate cells and human disease. J. Biol. Chem. 2019, 294, 2133−2141. (47) Chung, H. J.; Kim, W. K.; Oh, J.; Kim, M. R.; Shin, J. S.; Lee, J.; Ha, I. K.; Lee, S. K. Anti-osteoporotic activity of harpagoside by upregulation of the BMP2 and Wnt signaling pathways in osteoblasts and suppression of differentiation in osteoclasts. J. Nat. Prod. 2017, 80, 434−442. (48) Bez, M.; Sheyn, D.; Tawackoli, W.; Avalos, P.; Shapiro, G.; Giaconi, J. C.; Da, X. Y.; David, S. B.; Gavrity, J.; Awad, H. A.; Bae, H. W.; Ley, E. J.; Kremen, T. J.; Gazit, Z.; Ferrara, K. W.; Pelled, G.; Gazit, D. In situ bone tissue engineering via ultrasound-mediated gene delivery to endogenous progenitor cells in mini-pigs. Sci. Transl. Med. 2017, 9, No. eaal3128. (49) Li, Q.; Kannan, A.; Das, A.; DeMayo, F. J.; Hornsby, P. J.; Young, S. L.; Taylor, R. N.; Bagchi, M. K.; Bagchi, I. C. WNT4 acts downstream of BMP2 and functions via β-catenin signaling pathway to regulate human endometrial stromal cell differentiation. Endocrinology 2013, 154, 446−457.

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