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SCIENCE CHINA Materials, Volume 60, Issue 8: 777-788(2017) https://doi.org/10.1007/s40843-017-9068-6

Multifunctional Cu1.94S-Bi2S3@polymer nanocomposites for computed tomography imaging guided photothermal ablation

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  • ReceivedMay 2, 2017
  • AcceptedJun 25, 2017
  • PublishedJul 24, 2017

Abstract

The doping of radiocontrast agent such as bismuth (Bi) in copper chalcogenide nanocrystals for computed tomography (CT) imaging guided photothermal therapy (PTT) has drawn increasing attention. However, the doping of Bi often suffers from the weak CT signal due to the low Bi doping concentration and deteriorates the PTT efficacy of copper chalcogenides. Here we report a multifunctional nanoprobe by encapsulating both Cu1.94S and Bi2S3 nanocrystals into a biocompatible poly(amino acid) matrix with size of ~85 nm for CT imaging guided PTT. The amount of nanocrystals and the ratio of Cu1.94S-to-Bi2S3 in the multifunctional nanocomposites (NCs) are tunable toward both high photothermal conversion efficiency (~31%) and excellent CT imaging capability (27.8 HU g L−1). These NCs demonstrate excellent effects for photothermal ablation of tumors after intratumoral injection on 4T1 tumor-bearing mice. Our study may provide a facile strategy for the fabrication of multifunctional theranostics towards simultaneous strong CT signal and excellent PTT.


Funded by

This research was supported in part by the National Natural Science Foundation of China(21475007,21675009)

Fundamental Research Funds for the Central Universities(buctrc201608,buctrc201720)


Acknowledgment

This research was supported in part by the National Natural Science Foundation of China (21475007 and 21675009), and the Fundamental Research Funds for the Central Universities (buctrc201608 and buctrc201720). We also thank Prof. X. Zhang of Xiamen University for the help on the in vivo CT imaging and PTT, and the support from the “Public Hatching Platform for Recruited Talents of Beijing University of Chemical Technology”.


Interest statement

The authors declare that they have no conflict of interest.


Contributions statement

Wang L proposed the research direction and guided the project. Lu X, Li Y and Bai X designed and performed the experiments. Lu X, Hu G and Wang L analyzed and discussed the experimental results, and drafted the manuscript. All the authors checked and approved the manuscript.


Author information

Xiaoquan Lu is currently a third-year Master candidate in chemistry under the supervision of Prof. Leyu Wang at Beijing University of Chemical Technology (BUCT) since 2014. His research interest is focused on CT imaging and photothermal ablation.


Leyu Wang is a professor of chemistry at BUCT. He received his PhD in chemistry from Tsinghua University with Prof. Yadong Li in 2007. Then he joined Prof. Huang’s group at the University of California at Los Angeles (UCLA) as a postdoctoral researcher from 2007–2009. He moved to BUCT’s Chemistry Department in October 2009. His research interests span from the controlled synthesis of upconversion luminescence nanoparticles (UCNPs), localized surface plasmon resonance (LSPR) near-infrared (NIR) semiconductor NPs, magnetic nanomaterials, metal-semiconductor heteronanostructures, and molecularly imprinted polymers (MIPs) nanomaterials to the applications including electrocatalysis, artificial photosynthesis, biochemical sensing, multimodal imaging, drug/gene delivery and photothermo/chemo therapy.


Supplement

Supplementary information

Experimental details are available in the online version of the paper.


References

[1] Sugiura T, Matsuki D, Okajima J, et al. Photothermal therapy of tumors in lymph nodes using gold nanorods and near-infrared laser light with controlled surface cooling. Nano Res, 2015, 8: 3842-3852 CrossRef Google Scholar

[2] Song X, Chen Q, Liu Z. Recent advances in the development of organic photothermal nano-agents. Nano Res, 2015, 8: 340-354 CrossRef Google Scholar

[3] Yang Z, Ding X, Jiang J. Facile synthesis of magnetic-plasmonic nanocomposites as T 1 MRI contrast enhancing and photothermal therapeutic agents. Nano Res, 2016, 9: 787-799 CrossRef Google Scholar

[4] Xu S, Cui J, Wang L. Recent developments of low-toxicity NIR II quantum dots for sensing and bioimaging. TrAC Trends Anal Chem, 2016, 80: 149-155 CrossRef Google Scholar

[5] Huang S, Yan W, Hu G, et al. Facile and green synthesis of biocompatible and bioconjugatable magnetite nanofluids for high-resolutionT2 MRI contrast agents. J Phys Chem C, 2012, 116: 20558-20563 CrossRef Google Scholar

[6] Zhang R, Zhao J, Han G, et al. Real-time discrimination and versatile profiling of spontaneous reactive oxygen species in living organisms with a single fluorescent probe. J Am Chem Soc, 2016, 138: 3769-3778 CrossRef PubMed Google Scholar

[7] Mei Q, Zhang Z. Photoluminescent graphene oxide ink to print sensors onto microporous membranes for versatile visualization bioassays. Angew Chem Int Ed, 2012, 51: 5602-5606 CrossRef PubMed Google Scholar

[8] Liu R, Liu B, Guan G, et al. Multilayered shell SERS nanotags with a highly uniform single-particle Raman readout for ultrasensitive immunoassays. Chem Commun, 2012, 48: 9421-9423 CrossRef PubMed Google Scholar

[9] Zhang K, Zhou H, Mei Q, et al. Instant visual detection of trinitrotoluene particulates on various surfaces by ratiometric fluorescence of dual-emission quantum dots hybrid. J Am Chem Soc, 2011, 133: 8424-8427 CrossRef PubMed Google Scholar

[10] Lusic H, Grinstaff MW. X-ray-computed tomography contrast agents. Chem Rev, 2013, 113: 1641-1666 CrossRef PubMed Google Scholar

[11] Badea CT, Drangova M, Holdsworth DW, et al. In vivo small-animal imaging using micro-CT and digital subtraction angiography. Phys Med Biol, 2008, 53: R319-R350 CrossRef PubMed ADS Google Scholar

[12] Cheng L, Liu J, Gu X, et al. PEGylated WS2 nanosheets as a multifunctional theranostic agent for in vivo dual-modal CT/photoacoustic imaging guided photothermal therapy. Adv Mater, 2014, 26: 1886-1893 CrossRef PubMed Google Scholar

[13] Ai K, Liu Y, Liu J, et al. Large-scale synthesis of Bi2S3 nanodots as a contrast agent for in vivo X-ray computed tomography imaging. Adv Mater, 2011, 23: 4886-4891 CrossRef PubMed Google Scholar

[14] Haller C, Hizoh I. The cytotoxicity of iodinated radiocontrast agents on renal cells in vitro. Invest Radiol, 2004, 39: 149-154 CrossRef Google Scholar

[15] Leeuwenburgh MMN, Wiarda BM, Wiezer MJ, et al. Comparison of imaging strategies with conditional contrast-enhanced CT and unenhanced MR imaging in patients suspected of having appendicitis: a multicenter diagnostic performance study. Radiology, 2013, 268: 135-143 CrossRef PubMed Google Scholar

[16] Liu Y, Ai K, Lu L. Nanoparticulate X-ray computed tomography contrast agents: from design validation to in vivo applications. Acc Chem Res, 2012, 45: 1817-1827 CrossRef PubMed Google Scholar

[17] Lee N, Cho HR, Oh MH, et al. Multifunctional Fe3O4/TaOx core/shell nanoparticles for simultaneous magnetic resonance imaging and X-ray computed tomography. J Am Chem Soc, 2012, 134: 10309-10312 CrossRef PubMed Google Scholar

[18] Fang Y, Peng C, Guo R, et al. Dendrimer-stabilized bismuth sulfide nanoparticles: synthesis, characterization, and potential computed tomography imaging applications. Analyst, 2013, 138: 3172 CrossRef PubMed ADS Google Scholar

[19] Liu J, Zheng X, Yan L, et al. Bismuth sulfide nanorods as a precision nanomedicine for in vivo multimodal imaging-guided photothermal therapy of tumor. ACS Nano, 2015, 9: 696-707 CrossRef PubMed Google Scholar

[20] Zhang XD, Chen J, Min Y, et al. Metabolizable Bi2Se3 nanoplates: biodistribution, toxicity, and uses for cancer radiation therapy and imaging. Adv Funct Mater, 2014, 24: 1718-1729 CrossRef Google Scholar

[21] Elsabahy M, Heo GS, Lim SM, et al. Polymeric nanostructures for imaging and therapy. Chem Rev, 2015, 115: 10967-11011 CrossRef PubMed Google Scholar

[22] Rabin O, Manuel Perez J, Grimm J, et al. An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles. Nat Mater, 2006, 5: 118-122 CrossRef PubMed ADS Google Scholar

[23] Huang P, Bao L, Zhang C, et al. Folic acid-conjugated silica-modified gold nanorods for X-ray/CT imaging-guided dual-mode radiation and photo-thermal therapy. Biomaterials, 2011, 32: 9796-9809 CrossRef PubMed Google Scholar

[24] Liu Y, Miyoshi H, Nakamura M. Nanomedicine for drug delivery and imaging: a promising avenue for cancer therapy and diagnosis using targeted functional nanoparticles. Int J Cancer, 2007, 120: 2527-2537 CrossRef PubMed Google Scholar

[25] Xiao Q, Zheng X, Bu W, et al. A core/satellite multifunctional nanotheranostic for in vivo imaging and tumor eradication by radiation/photothermal synergistic therapy. J Am Chem Soc, 2013, 135: 13041-13048 CrossRef PubMed Google Scholar

[26] Cheng L, Yang K, Li Y, et al. Facile preparation of multifunctional upconversion nanoprobes for multimodal imaging and dual-targeted photothermal therapy. Angew Chem, 2011, 123: 7523-7528 CrossRef Google Scholar

[27] Cui J, Jiang R, Xu S, et al. Cu7S4 nanosuperlattices with greatly enhanced photothermal efficiency. Small, 2015, 11: 4183-4190 CrossRef PubMed Google Scholar

[28] Huang S, Liu J, He Q, et al. Smart Cu1.75S nanocapsules with high and stable photothermal efficiency for NIR photo-triggered drug release. Nano Res, 2015, 8: 4038-4047 CrossRef Google Scholar

[29] Li Y, Lu W, Huang Q, et al. Copper sulfide nanoparticles for photothermal ablation of tumor cells. Nanomedicine, 2010, 5: 1161-1171 CrossRef PubMed Google Scholar

[30] Xiao Z. CuS nanoparticles: clinically favorable materials for photothermal applications?. Nanomedicine, 2014, 9: 373-375 CrossRef PubMed Google Scholar

[31] Tian Q, Jiang F, Zou R, et al. Hydrophilic Cu9S5 nanocrystals: a photothermal agent with a 25.7% heat conversion efficiency for photothermal ablation of cancer cells in vivo. ACS Nano, 2011, 5: 9761-9771 CrossRef PubMed Google Scholar

[32] Mou J, Chen Y, Ma M, et al. Facile synthesis of liposome/Cu2−xS-based nanocomposite for multimodal imaging and photothermal therapy. Sci China Mater, 2015, 58: 294-301 CrossRef Google Scholar

[33] Chen H, Song M, Tang J, et al. Ultrahigh 19F loaded Cu1.75S nanoprobes for simultaneous 19F magnetic resonance imaging and photothermal therapy. ACS Nano, 2016, 10: 1355-1362 CrossRef Google Scholar

[34] Hu G, Tang J, Bai X, et al. Superfluorinated copper sulfide nanoprobes for simultaneous 19F magnetic resonance imaging and photothermal ablation. Nano Res, 2016, 9: 1630-1638 CrossRef Google Scholar

[35] Jia GZ, Lou WK, Cheng F, et al. Excellent photothermal conversion of core/shell CdSe/Bi2Se3 quantum dots. Nano Res, 2015, 8: 1443-1453 CrossRef Google Scholar

[36] Yi X, Yang K, Liang C, et al. Imaging-guided combined photothermal and radiotherapy to treat subcutaneous and metastatic tumors using iodine-131-doped copper sulfide nanoparticles. Adv Funct Mater, 2015, 25: 4689-4699 CrossRef Google Scholar

[37] Xi G, Ouyang S, Li P, et al. Ultrathin W18O49 nanowires with diameters below 1 nm: synthesis, near-infrared absorption, photoluminescence, and photochemical reduction of carbon dioxide. Angew Chem Int Ed, 2012, 51: 2395-2399 CrossRef PubMed Google Scholar

[38] Tian Q, Hu J, Zhu Y, et al. Sub-10 nm Fe3O4@Cu2–xS core-shell nanoparticles for dual-modal imaging and photothermal therapy. J Am Chem Soc, 2013, 135: 8571-8577 CrossRef PubMed Google Scholar

[39] Zha Z, Yue X, Ren Q, et al. Uniform polypyrrole nanoparticles with high photothermal conversion efficiency for photothermal ablation of cancer cells. Adv Mater, 2013, 25: 777-782 CrossRef PubMed Google Scholar

[40] Liu J, Wang P, Zhang X, et al. Rapid degradation and high renal clearance of Cu3BiS3 nanodots for efficient cancer diagnosis and photothermal therapy in vivo. ACS Nano, 2016, 10: 4587-4598 CrossRef Google Scholar

[41] Li J, Zhong H, Liu H, et al. One dimensional ternary Cu-Bi-S based semiconductor nanowires: synthesis, optical and electrical properties. J Mater Chem, 2012, 22: 17813-17819 CrossRef Google Scholar

[42] Li H, Zhang Q, Pan A, et al. Single-crystalline Cu4Bi4S9 nanoribbons: facile synthesis, growth mechanism, and surface photovoltaic properties. Chem Mater, 2011, 23: 1299-1305 CrossRef Google Scholar

[43] Temple DJ, Kehoe AB, Allen JP, et al. Geometry, electronic structure, and bonding in CuMCh2 (M = Sb, Bi; Ch = S, Se): alternative solar cell absorber materials?. J Phys Chem C, 2012, 116: 7334-7340 CrossRef Google Scholar

[44] Huang S, Bai M, Wang L. General and facile surface functionalization of hydrophobic nanocrystals with poly(amino acid) for cell luminescence imaging. Sci Rep, 2013, 3: 2023-2026 CrossRef PubMed ADS Google Scholar

[45] Deng M, Tu N, Bai F, et al. Surface functionalization of hydrophobic nanocrystals with one particle per micelle for bioapplications. Chem Mater, 2012, 24: 2592-2597 CrossRef Google Scholar

[46] Roper DK, Ahn W, Hoepfner M. Microscale heat transfer transduced by surface plasmon resonant gold nanoparticles. J Phys Chem C, 2007, 111: 3636-3641 CrossRef PubMed Google Scholar

[47] Huang S, Peng S, Li Y, et al. Development of NIR-II fluorescence image-guided and pH-responsive nanocapsules for cocktail drug delivery. Nano Res, 2015, 8: 1932-1943 CrossRef Google Scholar

[48] Kang HS, Yang SR, Kim JD, et al. Effects of grafted alkyl groups on aggregation behavior of amphiphilic poly(aspartic acid). Langmuir, 2001, 17: 7501-7506 CrossRef Google Scholar

[49] Wang H, Wang L. One-pot syntheses and cell imaging applications of poly(amino acid) coated LaVO4:Eu3+ luminescent nanocrystals. Inorg Chem, 2013, 52: 2439-2445 CrossRef PubMed Google Scholar

[50] Zhou C, Hao G, Thomas P, et al. Near-infrared emitting radioactive gold nanoparticles with molecular pharmacokinetics. Angew Chem Int Ed, 2012, 51: 10118-10122 CrossRef PubMed Google Scholar

[51] Prescott JH, Lipka S, Baldwin S, et al. Chronic, programmed polypeptide delivery from an implanted, multireservoir microchip device. Nat Biotechnol, 2006, 24: 437-438 CrossRef PubMed Google Scholar

[52] Xiao Q, Bu W, Ren Q, et al. Radiopaque fluorescence-transparent TaOx decorated upconversion nanophosphors for in vivo CT/MR/UCL trimodal imaging. Biomaterials, 2012, 33: 7530-7539 CrossRef PubMed Google Scholar

[53] Yang W, Guo W, Le W, et al. Albumin-bioinspired Gd:CuS nanotheranostic agent for in vivo photoacoustic/magnetic resonance imaging-guided tumor-targeted photothermal therapy. ACS Nano, 2016, 10: 10245-10257 CrossRef Google Scholar

[54] Zheng M, Li Y, Liu S, et al. One-pot to synthesize multifunctional carbon dots for near infrared fluorescence imaging and photothermal cancer therapy. ACS Appl Mater Interfaces, 2016, 8: 23533-23541 CrossRef Google Scholar

[55] Zhou B, Li Y, Niu G, et al. Near-infrared organic dye-based nanoagent for the photothermal therapy of cancer. ACS Appl Mater Interfaces, 2016, 8: 29899-29905 CrossRef Google Scholar

[56] Li Y, Bai X, Xu M, et al. Photothermo-responsive Cu7S4@polymer nanocarriers with small sizes and high efficiency for controlled chemo/photothermo therapy. Sci China Mater, 2016, 59: 254-264 CrossRef Google Scholar

  • Scheme 1

    Schematic illustration for the fabrication and CT-guided PTT of the Cu1.94S-Bi2S3@PSIOAm multifunctional nanocomposites.

  • Figure 1

    TEM images of Cu1.94S NPs (a), Bi2S3 nanorods (b) as well as Cu1.94S-Bi2S3@PSIOAm NCs (c and d), and DLS size distribution of NCs (e).

  • Figure 2

    (a) XRD pattern of Cu1.94S-Bi2S3@PSIOAm NCs. (b) FTIR spectra of the Cu1.94S NPs, Bi2S3 nanorods, PSIOAm and the NCs. (c) The monitored temperature profiles of the NCs synthesized with various Cu-to-Bi ratios, under the irradiation of 808-nm laser (1.0 W cm−2) for 6 min, followed by cooling naturally with laser light turned off. The dosage of Bi2S3 is fixed at 0.7 mg and the ratio of Cu-to-Bi in NCs was 9.07:1 (S2), 17.2:1 (S3) and 29.0:1 (S4), respectively. The nanocomposite sample prepared with only Bi2S3(0.7 mg) was denoted as S1. The concentration of the NCs was 0.3 mg mL−1.

  • Figure 3

    (a) Photothermal images of Cu1.94S-Bi2S3@PSIOAm NCs colloids under the irradiation of 808-nm light at different power densities and time intervals. (b) The temperature elevation profiles of the NCs colloids under continuous irradiation of 808-nm light at various power densities. The NCs concentration was 0.4 mg mL−1.

  • Figure 4

    Cell viability tests of NCs in the absence (a) and presence (b) of 808-nm light irradiation (1.0 W cm−2, 5 min) after incubation with HeLa cells for 24 h.

  • Figure 5

    In vitro CT images (a) and plot (b) of CT values (HU) versus the concentrations of Cu1.94S-Bi2S3@PSIOAm NCs colloidal solution. The concentration of Bi in each colloidal solution is 0.0, 0.09, 0.18, 0.36, 0.78, and 1.14 mg mL−1.

  • Figure 6

    (a) In vivo CT images of 4T1 tumor-bearing mice before and after intra-tumor injection of NCs nanoprobe solution (100 μL, 24 mg mL−1); In vivo photothermal images of the tumor-bearing mice after intra-tumor injection of NCs under irradiation (808 nm, 1.0 W cm−2) for different time intervals (b), and temperature evolution profile (c) of the tumor under 808-nm laser irradiation (1.0 W cm−2) for 0–10 min.

  • Figure 7

    Evolution plots of the tumor size (a) and the mouse body weight (b) after photothermal treatment under 808-nm laser irradiation with a power density of 1.0 W cm−2 for 10 min. 100 μL, 24 mg mL−1 of the nanoprobe solution was administered by intra-tumor injection; 100 μL of PBS solution (pH 7.4) was injected for the control group.

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