Abstract
Purpose
To develop a near-infrared (NIR) light-sensitive liposome, which contains hollow gold nanospheres (HAuNS) and doxorubicin (DOX), and evaluate their potential utility for enhancing antitumor activity and controlling drug release.
Methods
The liposomes (DOX&HAuNS-TSL) were designed based on a thermal sensitive liposome (TSL) formulation, and hydrophobically modified HAuNS were attached onto the membrane of the liposomes. The behavior of DOX release from the liposomes was investigated by the dialysis, diffusion in agarose gel and cellular uptake of the drug. The biodistribution of DOX&HAuNS-TSL was assessed by i.v. injection in tumor-bearing nude mice. Antitumor efficacy was evaluated both histologically using excised tissue and intuitively by measuring the tumor size and weight.
Results
Rapid and repetitive DOX release from the liposomes (DOX&HAuNS-TSL), could be readily achieved upon NIR laser irradiation. The treatment of tumor cells with DOX&HAuNS-TSL followed by NIR laser irradiation showed significantly greater cytotoxicity than the treatment with DOX&HAuNS-TSL alone, DOX-TSL alone (chemotherapy alone) and HAuNS-TSL plus NIR laser irradiation (Photothermal ablation, PTA, alone). In vivo antitumor study indicated that the combination of simultaneous photothermal and chemotherapeutic effect mediated by DOX&HAuNS-TSL plus NIR laser presented a significantly higher antitumor efficacy than the PTA alone mediated by HAuNS-TSL plus NIR laser irradiation.
Conclusions
Our study could be as the valuable reference and direction for the clinical application of PTA in tumor therapy.






Similar content being viewed by others
Explore related subjects
Discover the latest articles and news from researchers in related subjects, suggested using machine learning.References
Loo C, Lowery A, Halas N, West J, Drezek R. Immunotargeted nanoshells for integrated cancer imaging and therapy. Nano Lett. 2005;5:709–11.
Schwartz JA, Shetty AM, Price RE, Stafford RJ, Wang JC, Uthamanthil RK, et al. Feasibility study of particle-assisted laser ablation of brain tumors in orthotopic canine model. Cancer Res. 2009;69:1659–67.
von Maltzahn G, Park J-H, Agrawal A, Bandaru NK, Das SK, Sailor MJ, et al. Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas. Cancer Res. 2009;69:3892–900.
Chen J, Glaus C, Laforest R, Zhang Q, Yang M, Gidding M, et al. Gold nanocages as photothermal transducers for cancer treatment. Small. 2010;6:811–7.
Abdulla-Al-Mamun M, Kusumoto Y, Mihata A, Islam MS, Ahmmad B. Plasmon-induced photothermal cell-killing effect of gold colloidal nanoparticles on epithelial carcinoma cells. Photochem Photobiol Sci. 2009;8:1125–9.
Wong SL, Mangu PB, Choti MA, Crocenzi TS, Dodd 3rd GD, Dorfman GS, et al. American Society of Clinical Oncology 2009 clinical evidence review on radiofrequency ablation of hepatic metastases from colorectal cancer. J Clin Oncol. 2010;28:493–508.
Dooley WC, Vargas HI, Fenn AJ, Tomaselli MB, Harness JK. Focused microwave thermotherapy for preoperative treatment of invasive breast cancer: a review of clinical studies. Ann Surg Oncol. 2010;17:1076–93.
Orsi F, Zhang L, Arnone P, Orgera G, Bonomo G, Vigna PD, et al. High-intensity focused ultrasound ablation: effective and safe therapy for solid tumors in difficult locations. AJR Am J Roentgenol. 2010;195:W245–52.
Kennedy LC, Bickford LR, Lewinski NA, Coughlin AJ, Hu Y, Day ES, et al. A new era for cancer treatment: gold–nanoparticle–mediated thermal therapies. Small. 2011;7:169–83.
Pilot Study of AuroLase Therapy in Refractory and/or Recurrent Tumors of the Head and Neck, http://clinicaltrials.gov/ct2/ show/NCT00848042 2010; (accessed September 2010).
Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2007;2:751–60.
Sengupta S, Eavarone D, Capila I, Zhao G, Watson N, Kiziltepe T, et al. Temporal targeting of tumour cells and neovasculature with a nanoscale delivery system. Nature. 2005;436:568–72.
Abraham SA, Waterhouse DN, Mayer LD, Cullis PR, Madden TD, Bally MB. The liposomal formulation of doxorubicin. Methods Enzymol. 2005;391:71–9.
Obata Y, Tajima S, Takeoka S. Evaluation of pH-responsive liposomes containing amino acid-based zwitterionic lipids for improving intracellular drug delivery in vitro and in vivo. J Control Release. 2010;142:267–76.
Ducat E, Deprez J, Gillet A, Noel A, Evrard B, Peulen O, et al. Nuclear delivery of a therapeutic peptide by long circulating pH-sensitive liposomes: benefits over classical vesicles. Int J Pharm. 2011;420:319–32.
Paasonen L, Laaksonen T, Johans C, Yliperttula M, Kontturi K, Urtti A. Gold nanoparticles enable selective light-induced contents release from liposomes. J Control Release. 2007;122:86–93.
Paasonen L, Sipila T, Subrizi A, Laurinmaki P, Butcher SJ, Rappolt M, et al. Gold-embedded photosensitive liposomes for drug delivery: triggering mechanism and intracellular release. J Control Release. 2010;147:136–43.
Stadler B, Chandrawati R, Price AD, Chong SF, Breheney K, Postma A, et al. A microreactor with thousands of subcompartments: enzyme-loaded liposomes within polymer capsules. Angew Chem Int Ed Engl. 2009;48:4359–62.
Vamvakaki V, Fournier D, Chaniotakis NA. Fluorescence detection of enzymatic activity within a liposome based nano-biosensor. Biosens Bioelectron. 2005;21:384–8.
Dromi S, Frenkel V, Luk A, Traughber B, Angstadt M, Bur M, et al. Pulsed-high intensity focused ultrasound and low temperature-sensitive liposomes for enhanced targeted drug delivery and antitumor effect. Clin Cancer Res. 2007;13:2722–7.
Li L, ten Hagen TL, Schipper D, Wijnberg TM, van Rhoon GC, Eggermont AM, et al. Triggered content release from optimized stealth thermosensitive liposomes using mild hyperthermia. J Control Release. 2010;143:274–9.
Agarwal A, Mackey MA, El-Sayed MA, Bellamkonda RV. Remote triggered release of doxorubicin in tumors by synergistic application of thermosensitive liposomes and gold nanorods. ACS Nano. 2011;5:4919–26.
Park JH, von Maltzahn G, Ong LL, Centrone A, Hatton TA, Ruoslahti E, et al. Cooperative nanoparticles for tumor detection and photothermally triggered drug delivery. Adv Mater. 2010;22:880–5.
Leungand SJ, Romanowski M. NIR-activated content release from plasmon resonant liposomes for probing single-cell responses. ACS Nano. 2012;6:9383–91.
S.J. Leung, M.C. Bobnick, and M. Romanowski. Plasmon resonant gold-coated liposomes for spectrally controlled content release. Proc Soc Photo Opt Instrum Eng. 2010;7577.
Schwartzberg AM, Oshiro TY, Zhang JZ, Huser T, Talley CE. Improving nanoprobes using surface-enhanced Raman scattering from 30-nm hollow gold particles. Anal Chem. 2006;78:4732–6.
Lu W, Huang Q, Ku G, Wen X, Zhou M, Guzatov D, et al. Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres. Biomaterials. 2010;31:2617–26.
Lu W, Xiong C, Zhang G, Huang Q, Zhang R, Zhang JZ, et al. Targeted photothermal ablation of murine melanomas with melanocyte-stimulating hormone analog-conjugated hollow gold nanospheres. Clin Cancer Res. 2009;15:876–86.
You J, Zhang G, Li C. Exceptionally high payload of doxorubicin in hollow gold nanospheres for near-infrared light-triggered drug release. ACS Nano. 2010;4:1033–41.
You J, Shao R, Wei X, Gupta S, Li C. Near-infrared light triggers release of Paclitaxel from biodegradable microspheres: photothermal effect and enhanced antitumor activity. Small. 2010;6:1022–31.
You J, Zhang R, Zhang G, Zhong M, Liu Y, Van Pelt CS, et al. Photothermal-chemotherapy with doxorubicin-loaded hollow gold nanospheres: A platform for near-infrared light-trigged drug release. J Control Release. 2012;158:319–28.
de Smet M, Langereis S. S.v. den Bosch, and H. Grüll. Temperature-sensitive liposomes for doxorubicin delivery under MRI guidance. J Control Release. 2010;143:120–7.
Noble RP, Hatch FT, Mazrimas JA, Lindgren FT, Jensen LC, Adamson GL. Comparison of lipoprotein analysis by agarose gel and paper electrophoresis with analytical ultracentrifugation. Lipids. 1969;4:55–9.
Wu G, Mikhailovsky A, Khant HA, Fu C, Chiu W, Zasadzinski JA. Remotely triggered liposome release by near-infrared light absorption via hollow gold nanoshells. J Am Chem Soc. 2008;130:8175–7.
Hahnand GM, Shiu EC. Effect of pH and elevated temperatures on the cytotoxicity of some chemotherapeutic agents on Chinese hamster cells in vitro. Cancer Res. 1983;43:5789–91.
Yooand J, Lee YJ. Effect of hyperthermia and chemotherapeutic agents on TRAIL-induced cell death in human colon cancer cells. J Cell Biochem. 2008;103:98–109.
Adachi S, Kokura S, Okayama T, Ishikawa T, Takagi T, Handa O, et al. Effect of hyperthermia combined with gemcitabine on apoptotic cell death in cultured human pancreatic cancer cell lines. Int J Hyperth. 2009;25:210–9.
Ko SH, Ueno T, Yoshimoto Y, Yoo JS, Abdel-Wahab OI, Abdel-Wahab Z, et al. Optimizing a novel regional chemotherapeutic agent against melanoma: hyperthermia-induced enhancement of temozolomide cytotoxicity. Clin Cancer Res. 2006;12:289–97.
Acknowledgments and disclosures
This work was supported by the National Nature Science Foundation of China (81001411), Qianjiang Talent Plan Program of Zhejiang Province (2013R10043), the National Basic Research Program of China (973 Program) under Contract 2009CB930300, National Nature Science Foundation of China (81072583), and part by the National Cancer Institute (U54CA151668).
Author information
Authors and Affiliations
Corresponding authors
Electronic supplementary material
Below is the link to the electronic supplementary material.
ESM 1
(DOC 363 kb)
Rights and permissions
About this article
Cite this article
You, J., Zhang, P., Hu, F. et al. Near-Infrared Light-Sensitive Liposomes for the Enhanced Photothermal Tumor Treatment by the Combination with Chemotherapy. Pharm Res 31, 554–565 (2014). https://doi.org/10.1007/s11095-013-1180-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11095-013-1180-7