SCIENCE CHINA Materials, Volume 58, Issue 4: 294-301(2015) https://doi.org/10.1007/s40843-015-0044-3

Facile synthesis of liposome/Cu2xS-based nanocomposite for multimodal imaging and photothermal therapy

More info
  • ReceivedMar 5, 2015
  • AcceptedApr 10, 2015
  • PublishedApr 24, 2015


A kind of multifunctional perfluoropentane (PFP) and ultrasmall Cu2−xS nanodots (u-Cu2−xS NDs) co-incorporated liposome (PFP@u-Cu2−xS NDs@liposome) nanocomposite has been facilely and successfully synthesized for enhanced ultrasound/infrared thermal/photoacoustic multimodal imaging and photothermal therapy upon near infrared (NIR) laser irradiation. Such a liposome-based nanocomposite possesses a number of advantages, such as high dispersity and stability, excellent biocompatibility, small particle size (<100 nm), well-defined core/shell structure, strong NIR absorption and photo-triggered vaporization of PFP, etc. The detailed in vitro investigations demonstrate that the as-synthesized PFP@ u-Cu2−xS NDs@liposome nanocomposite is capable of enhancing the contrasts of ultrasound/infrared thermal/photoacoustic multimodal imaging, and substantially improving the photothermal therapeutic efficacy. This novel liposome-based theranostic nanoplatform shows great potentials in the future cancer diagnosis and therapy.


This work was supported by the National Basic Research Program of China (2011CB707905), China National Funds for Distinguished Young Scientists (51225202), and

Interest statement

The authors declare that they have no conflict of interest.

Contributions statement

Shi J and Chen H initiated and guided the work. Mou J designed and conducted the experiments. Chen Y, Ma M, Zhang K gave useful suggestions. Wei C set up the experimental devices.

Author information

Juan Mou received her BSc degree at China University of Geosciences (Wuhan) (2007). She is now a PhD candidate at Shanghai Institute of Ceramics, Chinese Academy of Sciences (SICCAS). Her research interest includes the design, synthesis and biomedical applications of novel photothermal and photodynamic therapy materials.

Hangrong Chen received her PhD degree in SICCAS (2001). She is now a professor of SICCAS. Her research areas include the synthesis of mesoporous materials, multifunctional inorganic biomedical nanomaterials, and novel environmental catalytic materials. She has published more than 150 scientific papers which have been cited more than 4600 times by other scientists with an h-index of 38 (2014).

Jianlin Shi received his PhD degree in SICCAS (1989). He is now a professor of SICCAS. His research areas include the synthesis of mesoporous materials, mesoporous-based nano-composites, and their catalytic, biomedical and optical applications. He has published more than 300 scientific papers which have been cited more than 12,000 times by other scientists with an h-index of 59 (2014).


Supplementary information

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


[1] Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014. CA-Cancer J Clin, 2014, 64: 9–29. Google Scholar

[2] Fass L. Imaging and cancer: a review. Mol Oncol, 2008, 2: 115–152. Google Scholar

[3] Brody H. Medical imaging. Nature, 2013, 502: S81. Google Scholar

[4] Glasspool RM, Evans TRJ. Clinical imaging of cancer metastasis. Eur J Cancer, 2000, 36: 1661–1670. Google Scholar

[5] Manning MR, Cetas TC, Miller RC, et al. Clinical hyperthermia: results of a phase I trial employing hyperthermia alone or in combination with external beam or interstitial radiotherapy. Cancer, 1982, 49: 205–216. Google Scholar

[6] D’Amico AV, Whittington R, Malkowicz S, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA, 1998, 280: 969–974. Google Scholar

[7] Nelson H, Petrelli N, Carlin A, et al. Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst, 2001, 93: 583–596. Google Scholar

[8] Stewart LA. Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet, 2002, 359: 1011–1018. Google Scholar

[9] Dougherty TJ, Gomer CJ, Henderson BW, et al. Photodynamic therapy. J Natl Cancer Inst, 1998, 90: 889–905. Google Scholar

[10] Huang X, El-Sayed IH, Qian W, et al. Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. J Am Chem Soc, 2006, 128: 2115–2120. Google Scholar

[11] Lal S, Clare SE, Halas NJ. Nanoshell-enabled photothermal cancer therapy: impending clinical impact. Acc Chem Res, 2008, 41: 1842–1851. Google Scholar

[12] Gobin AM, Lee MH, Halas NJ, et al. Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy. Nano Lett, 2007, 7: 1929–1934. Google Scholar

[13] Loo C, Lowery A, Halas N, et al. Immunotargeted nanoshells for integrated cancer imaging and therapy. Nano Lett, 2005, 5: 709–711. Google Scholar

[14] Huang Y, He S, Cao W, et al. Biomedical nanomaterials for imaging-guided cancer therapy. Nanoscale, 2012, 4: 6135–6149. Google Scholar

[15] Yang K, Hu L, Ma X, et al. Multimodal imaging guided photothermal therapy using functionalized graphene nanosheets anchored with magnetic nanoparticles. Adv Mater, 2012, 24: 1868–1872. Google Scholar

[16] Zhou M, Zhang R, Huang M, et al. A chelator-free multifunctional [64Cu]CuS nanoparticle platform for simultaneous micro-PET/CT imaging and photothermal ablation therapy. J Am Chem Soc, 2010, 132: 15351–15358. Google Scholar

[17] Jin Y, Li Y, Ma X, et al. Encapsulating tantalum oxide into polypyrrole nanoparticles for X-ray CT/photoacoustic bimodal imaging-guided photothermal ablation of cancer. Biomaterials, 2014, 35: 5795–5804. Google Scholar

[18] Deshpande N, Needles A, Willmann JK. Molecular ultrasound imaging: current status and future directions. Clin Radiol, 2010, 65: 567–581. Google Scholar

[19] Pignoli P, Tremoli E, Poli A, et al. Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation, 1986, 74: 1399–406. Google Scholar

[20] Fenster A, Downey DB. 3-D ultrasound imaging: a review. Eng Med Biol, IEEE, 1996, 15: 41–51. Google Scholar

[21] Herment A, Guglielmi JP, Dumee P, et al. Limitations of ultrasound imaging and image restoration. Ultrasonics, 1987, 25: 267–273. Google Scholar

[22] Sanchis-Sanchez E, Vergara-Hernandez C, Cibrian RM, et al. Infrared thermal imaging in the diagnosis of musculoskeletal injuries: a systematic review and meta-analysis. AJR Am J Roentgenol, 2014, 203: 875–882. Google Scholar

[23] Ring EF, Ammer K. Infrared thermal imaging in medicine. Physiol Meas, 2012, 33: R33–46. Google Scholar

[24] Lahiri BB, Bagavathiappan S, Jayakumar T, et al. Medical applications of infrared thermography: a review. Infrared Phys Technol, 2012, 55: 221–235. Google Scholar

[25] Wang LV, Hu S. Photoacoustic tomography: in vivo imaging from organelles to organs. Science, 2012, 335: 1458–1462. Google Scholar

[26] Wang X, Pang Y, Ku G, et al. Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain. Nat Biotechnol, 2003, 21: 803–806. Google Scholar

[27] Beard P. Biomedical photoacoustic imaging. Interface Focus, 2011, 1: 602–631. Google Scholar

[28] Xu M, Wang LV. Photoacoustic imaging in biomedicine. Rev Sci Instrum, 2006, 77: 041101. Google Scholar

[29] Martina MS, Fortin JP, Ménager C, et al. Generation of superparamagnetic liposomes revealed as highly efficient MRI contrast agents for in vivo imaging. J Am Chem Soc, 2005, 127: 10676–10685. Google Scholar

[30] Marie H, Lemaire L, Franconi F, et al. Superparamagnetic liposomes for MRI monitoring and external magnetic field-induced selective targeting of malignant brain tumors. Adv Funct Mater, 2015, 8: 1258–1269. Google Scholar

[31] Lozano N, Al-Jamal WT, Taruttis A, et al. Liposome-gold nanorod hybrids for high-resolution visualization deep in tissues. J Am Chem Soc, 2012, 134: 13256–13258. Google Scholar

[32] Langereis S, Keupp J, van Velthoven JLJ, et al. A temperature-sensitive liposomal 1H CEST and 19F contrast agent for MR image-guided drug delivery. J Am Chem Soc, 2009, 131: 1380–1381. Google Scholar

[33] Hagisawa K, Nishioka T, Suzuki R, et al. Enhancement of ultrasonic thrombus imaging using novel liposomal bubbles targeting activated platelet glycoprotein IIb/IIIa complex-in vitro and in vivo study. Int J Cardiol, 152: 202–206. Google Scholar

[34] Hagisawa K, Nishioka T, Suzuki R, et al. Thrombus-targeted perfluorocarbon-containing liposomal bubbles for enhancement of ultrasonic thrombolysis: in vitro and in vivo study. J Thromb Haemost JTH, 2013, 11: 1565–1573. Google Scholar

[35] Strohm E, Rui M, Gorelikov I, et al. Vaporization of perfluorocarbon droplets using optical irradiation. Biomed Opt Express, 2011, 2: 1432–1442. Google Scholar

[36] Lindner JR. Microbubbles in medical imaging: current applications and future directions. Nat Rev Drug Discovery, 2004, 3: 527–533. Google Scholar

[37] Wilson K, Homan K, Emelianov S. Biomedical photoacoustics beyond thermal expansion using triggered nanodroplet vaporization for contrast-enhanced imaging. Nat Commun, 2012, 3: 618. Google Scholar

[38] Strohm E, Rui M, Gorelikov I, et al. Vaporization of perfluorocarbon droplets using optical irradiation. Biomed Opts express, 2011, 2: 1432–1442. Google Scholar

[39] Hannah AS, VanderLaan D, Chen YS, et al. Photoacoustic and ultrasound imaging using dual contrast perfluorocarbon nanodroplets triggered by laser pulses at 1064 nm. Biomed Opt Express, 2014, 5: 3042–3052. Google Scholar

[40] Hannah A, Luke G, Wilson K, et al. Indocyanine green-loaded photoacoustic nanodroplets: dual contrast nanoconstructs for enhanced photoacoustic and ultrasound imaging. ACS Nano, 2013, 8: 250–259. Google Scholar

[41] Ma M, Xu H, Chen H, et al. A drug–perfluorocarbon nanoemulsion with an ultrathin silica coating for the synergistic effect of chemotherapy and ablation by high-intensity focused ultrasound. Adv Mater, 2014, 26: 7378–7385. Google Scholar

[42] Zhou Y, Wang Z, Chen Y, et al. Microbubbles from gas-generating perfluorohexane nanoemulsions for targeted temperature-sensitive ultrasonography and synergistic HIFU ablation of tumors. Adv Mater, 2013, 25: 4123–4130. Google Scholar

[43] Sun Y, Wang Y, Niu C, et al. Laser-activatible PLGA microparticles for image-guided cancer therapy in vivo. Adv Funct Mater, 2014, 24: 7674–7680. Google Scholar

[44] Luther JM, Jain PK, Ewers T, et al. Localized surface plasmon resonances arising from free carriers in doped quantum dots. Nat Mater, 2011, 10: 361–366. Google Scholar

[45] Wei T, Liu Y, Dong W, et al. Surface-dependent localized surface plasmon resonances in CuS nanodisks. ACS Appl Mater Interfaces, 2013, 5: 10473–10477. Google Scholar

[46] Liu X, Swihart MT. Heavily-doped colloidal semiconductor and metal oxide nanocrystals: an emerging new class of plasmonic nanomaterials. Chem Soc Rev, 2014, 43: 3908–3920. Google Scholar

[47] Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol, 1965, 13: 238–258. Google Scholar

[48] Mou J, Li P, Liu C, et al. Ultrasmall Cu2−xS nanodots for highly efficient photoacoustic imaging-guided photothermal therapy. Small, doi: 10.1002/smll.201403249. Google Scholar

  • Scheme 1

    Schematic illustration of the as-synthesized PFP@u-Cu2−xS NDs@liposome for enhanced ultrasound/infrared thermal/photoacoustic multimodal imaging and photothermal therapy under NIR laser irradiation.

  • Figure 1

    TEM images of blank liposome (a) and oleylamine-capped u-Cu2−xS NDs (b). STEM (c) and HAADF-STEM image (d) of the PFP@u-Cu2−xS NDs@liposome. (e) UV-Vis absorption spectra of PFP@u-Cu2−xS NDs@liposome dispersions at different Cu2+ concentrations and (f) the corresponding linear fitting plots of absorbance vs. Cu2+ concentration at 1064 nm.

  • Figure 2

    Optical microscopic images of u-Cu2−xS NDs@liposome (a, b) and PFP@u-Cu2−xS NDs@liposome dispersion immersed in hot water (60°C) (c, d), and exposed to NIR laser irradiation (980 nm, 1.41 W cm−2, 5 min) (e, f).

  • Figure 3

    Ultrasound images of PFP@liposome (a, b) and PFP@u-Cu2−xS NDs@liposome dispersion (c, d) before and after NIR laser irradiation for 5 min. Infrared thermal images (e–h) of water droplet and aqueous droplets containing PFP@u-Cu2−xS NDs@liposome (Cu2+ concentration, C1: 12.5 ppm, C2: 50 ppm) under NIR laser irradiation at different time intervals. (i) Linear plot of photoacoustic signal intensity vs. Cu2+ concentration, the inset shows the corresponding photoacoustic images of agar gel cylinders containing PFP@u-Cu2−xS NDs@liposome at varied Cu2+ concentrations. (j) Temperature elevations of the PFP@u-Cu2−xS NDs@liposome dispersion exposed to NIR laser irradiation (980 nm, 1.41 W cm−2) vs. Cu2+ concentration.

  • Figure 4

    Optical microscopic images (a–d) and CLSM images (e–h) of HeLa cells stained with trypan blue, calcein-AM and prodium iodide (PI) after different treatments: (a, e) without treatment as a control; (b, f) treated with PFP@u-Cu2−xS NDs@liposome alone; (c, g) treated with NIR laser irradiation alone; (d, h) treated with the PFP@u-Cu2−xS NDs@liposome and NIR laser irradiation (980 nm, 1.41 W cm−2) together. All the scale bars in (a–h) are 50 μm.

Copyright 2020 Science China Press Co., Ltd. 《中国科学》杂志社有限责任公司 版权所有