Skip to main content
SpringerLink
Log in

In situ synthesis of gold nanostars within liposomes for controlled drug release and photoacoustic imaging

脂质体内金纳米星的原位合成以及在药物释放和光声造影上的应用

  • Articles
  • Published:
Science China Materials Aims and scope Submit manuscript

Abstract

This report describes the design and synthesis of gold nanostars (AuNSs) containing liposomes by the in situ reduction of gold precursor, HAuCl4 (pre-encapsulated within the liposomes) through HEPES diffusion and reduction. Compared with the conventional process that encapsulates the pre-synthesized gold nanoparticles into liposomes during the thin-film hydration step, this facile and convenient method allows the formation and simultaneous encapsulation of AuNSs within liposomes. The absorption spectra of AuNSs can be tuned between visible and near infra-red (NIR) regions by controlling the size and morphology of AuNSs through varying the concentrations of HAuCl4 and HEPES. As a proof of concept, we demonstrate the synthesis of AuNSs with a maximum absorbance at 803 nmwithin the temperature-sensitive liposomes. These liposomes can produce stronger photoacoustic signals (1.5 fold) in the NIR region than blood. Furthermore, when there are drugs (i.e., doxorubicin) within these liposomes, the irradiation with the NIR pulse laser will disrupt the liposomes and trigger the 100% release of these pre-encapsulated drugs within 10 seconds. In comparison, there is neglectable contrast enhancement or minor release (10%) of drugs for the pure liposomes under the same conditions. Finally, cell experiment shows the potential therapeutic application of this system.

摘要

本文通过在脂质体内还原金的前体HAuCl4原位合成了金纳米星. 这种设计跟常用的在脂质体内装载金纳米球的方法相比, 优点是方 便快捷的同时实现了金纳米材料的形成和装载. 通过改变实验条件, 合成的金纳米星具有可控的尺寸, 以及在可见区到近红外区之间的可 控吸收光谱. 作为一个例子, 我们在脂质体内合成了最大吸收在803nm的金纳米星. 这种材料具有温度敏感性, 在近红外区可以产生比血液 好1.5倍的光声造影信号. 当我们把抗癌药物阿霉素装载到这种脂质体内时, 近红外区的激光照射可以在10秒内触发药物100%的释放. 相对应的, 不含纳米星的脂质体在同等条件下只能释放10%的药物, 也不具备光声造影的信号增强. 最后, 我们在癌细胞内测试了该脂质体的疗效, 初步验证了该体系的应用前景.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Alvarez-Lorenzo C, Bromberg L, Concheiro A. Light-sensitive intelligent drug delivery systems. Photochem Photobiol, 2009, 85: 848–860

    Article  Google Scholar 

  2. Movahedi F, Hu RG, Becker DL, et al. Stimuli-responsive liposomes for the delivery of nucleic acid therapeutics. Nanomed Nanotechnol Biol Med, 2015, 11: 1575–1584

    Article  Google Scholar 

  3. Leung SJ, Romanowski M. Light-activated content release from liposomes. Theranostics, 2012, 2: 1020–1036

    Article  Google Scholar 

  4. Pashkovskaya A, Kotova E, Zorlu Y, et al. Light-triggered liposomal release: membrane permeabilization by photodynamic action. Langmuir, 2010, 26: 5726–5733

    Article  Google Scholar 

  5. 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

    Article  Google Scholar 

  6. Taruttis A, Lozano N, Nunes A, et al. siRNA liposome-gold nanorod vectors for multispectral optoacoustic tomography theranostics. Nanoscale, 2014, 6: 13451–13456

    Article  Google Scholar 

  7. Mathiyazhakan M, Yang Y, Liu Y, et al. Non-invasive controlled release from gold nanoparticle integrated photo-responsive liposomes through pulse laser induced microbubble cavitation. Colloid Surf B-Biointerfaces, 2015, 126: 569–574

    Article  Google Scholar 

  8. Akbarzadeh A, Rezaei-Sadabady R, Davaran S, et al. Liposome: classification, preparation, and applications. Nanoscale Res Lett, 2013, 8: 102

    Article  Google Scholar 

  9. Xie J, Lee JY, Wang DIC. Seedless, surfactantless, high-yield synthesis of branched gold nanocrystals in HEPES buffer solution. Chem Mater, 2007, 19: 2823–2830

    Article  Google Scholar 

  10. Chen R, Wu J, Li H, et al. Fabrication of gold nanoparticleswith differentmorphologies in HEPES buffer. RareMet, 2010, 29: 180–186

    Google Scholar 

  11. Dua JS, Rana AC, Bhandari AK. Liposome: methods of preparation and applications. Int J Pharm Sci Res, 2012, 3: 14–20

    Google Scholar 

  12. Szoka F, Papahadjopoulos D. Comparative properties andmethods of preparation of lipid vesicles (liposomes). Annu Rev Biophys Bioeng, 1980, 9: 467–508

    Article  Google Scholar 

  13. Missirlis D, Kawamura R, Tirelli N, et al. Doxorubicin encapsulation and diffusional release from stable, polymeric, hydrogel nanoparticles. Eur J Pharm Sci, 2006, 29: 120–129

    Article  Google Scholar 

  14. Genç R, Ortiz M, O’Sullivan CK. Diffusion-controlled synthesis of gold nanoparticles: nano-liposomes as mass transfer barrier. J Nanopart Res, 2014, 16: 2329

    Article  Google Scholar 

  15. Anderson RR, Parrish JA. The optics of human skin. J Investig Dermatol, 1981, 77: 13–19

    Article  Google Scholar 

  16. Tsai CL, Chen JC, Wang WJ. Near-infrared absorption property of biological soft tissue constituents. J Med Biol Eng, 2001, 21: 7–14

    Google Scholar 

  17. Upputuri PK, Pramanik M. Pulsed laser diode based optoacoustic imaging of biological tissues. Biomed Phys Eng Express, 2015, 1: 045010

    Article  Google Scholar 

  18. Huang S, Upputuri PK, Liu H, et al. A dual-functional benzobisthiadiazole derivative as an effective theranostic agent for nearinfrared photoacoustic imaging and photothermal therapy. JMater Chem B, 2016, 4: 1696–1703

    Article  Google Scholar 

  19. Lu W, Huang Q, Ku G, et al. Photoacoustic imaging of livingmouse brain vasculature using hollow gold nanospheres. Biomaterials, 2010, 31: 2617–2626

    Article  Google Scholar 

  20. Xu J, Zhao Q, Jin Y, et al. High loading of hydrophilic/hydrophobic doxorubicin into polyphosphazene polymersome for breast cancer therapy. Nanomed Nanotechnol Biol Med, 2014, 10: 349–358

    Article  Google Scholar 

  21. Maiorano G, Rizzello L, Malvindi MA, et al. Monodispersed and size-controlled multibranched gold nanoparticles with nanoscale tuning of surface morphology. Nanoscale, 2011, 3: 2227–2232

    Article  Google Scholar 

  22. Liu Y, Yuan H, Fales A, et al. Multifunctional gold nanostars for molecular imaging and cancer therapy. Front Chem, 2015, 3: 51

    Article  Google Scholar 

  23. Bao C, Conde J, Pan F, et al. Gold nanoprisms as a hybrid in vivo cancer theranostic platform for in situ photoacoustic imaging, angiography, and localized hyperthermia. Nano Res, 2016, 9: 1043–1056

    Article  Google Scholar 

  24. Jiang Y, Deng Z, Yang D, et al. Gold nanoflowers for 3D volumetric molecular imaging of tumors by photoacoustic tomography. Nano Res, 2015, 8: 2152–2161

    Article  Google Scholar 

  25. Mou J, Chen Y, Ma M, et al. Facile synthesis of liposome/Cu2-xSbased nanocomposite for multimodal imaging and photothermal therapy. Sci China Mater, 2015, 58: 294–301

    Article  Google Scholar 

  26. Rai VN, Srivastava AK, Mukherjee C, et al. Surface enhanced absorption and transmission from dye coated gold nanoparticles in thin films. Appl Opt, 2012, 51: 2606–2615

    Article  Google Scholar 

  27. Ponce AM, Viglianti BL, Yu D, et al. Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects. J Natl Cancer Institute, 2007, 99: 53–63

    Article  Google Scholar 

  28. Kim MS, Lee DW, Park K, et al. Temperature-triggered tumor-specific delivery of anticancer agents by cRGD-conjugated thermosensitive liposomes. Colloid Surf B Biointerfaces, 2014, 116: 17–25

    Article  Google Scholar 

  29. Lapotko DO, Lukianova E, Oraevsky AA. Selective laser nano-thermolysis of human leukemia cells with microbubbles generated around clusters of gold nanoparticles. Lasers Surg Med, 2006, 38: 631–642

    Article  Google Scholar 

  30. Lukianova-Hleb EY, Belyanin A, Kashinath S, et al. Plasmonic nanobubble-enhanced endosomal escape processes for selective and guided intracellular delivery of chemotherapy to drug-resistant cancer cells. Biomaterials, 2012, 33: 1821–1826

    Article  Google Scholar 

  31. Hleb EY, Hafner JH, Myers JN, et al. LANTCET: elimination of solid tumor cells with photothermal bubbles generated around clusters of gold nanoparticles. Nanomedicine, 2008, 3: 647–667

    Article  Google Scholar 

Download references

Acknowledgments

The work was partially supported by NTU-Northwestern Institute for Nanomedicine (To Xu CJ), the Tier-2 Grant funded by theMinistry of Education in Singapore (ARC2/15: M4020238 to M.P.). Dhayani A thanks UGC for junior research fellowship. Vemula PK thanks DBT for Ramalingaswami ReEntry fellowship. We appreciateMr. Stanley Sim Siong Wei to help us draw the illustration.

Author information

Authors and Affiliations

  1. School of Chemical & Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore City, Singapore

    Malathi Mathiyazhakan, Paul Kumar Upputuri, Kathyayini Sivasubramanian, Kanyi Pu  (浦侃裔), Manojit Pramanik & Chenjie Xu  (徐臣杰)

  2. Institute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK-Campus, Bellary Road, Bangalore, India

    Ashish Dhayani & Praveen Kumar Vemula

  3. Ramalingaswami Re-Entry Fellow, Department of Biotechnology, New Delhi, 110003, India

    Praveen Kumar Vemula

  4. Division of Energy & Environment, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, China

    Peichao Zou  (邹培超) & Cheng Yang  (杨诚)

  5. NTU-Northwestern Institute for Nanomedicine, Nanyang Technological University, 50 Nanyang Avenue, Singapore City, Singapore

    Chenjie Xu  (徐臣杰)

Authors
  1. Malathi Mathiyazhakan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul Kumar Upputuri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kathyayini Sivasubramanian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ashish Dhayani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Praveen Kumar Vemula
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peichao Zou  (邹培超)
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kanyi Pu  (浦侃裔)
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Cheng Yang  (杨诚)
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Manojit Pramanik
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Chenjie Xu  (徐臣杰)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chenjie Xu  (徐臣杰).

Additional information

Malathi Mathiyazhakan studied industrial biotechnology at SASTRA University, India. As an undergraduate, she conducted research on host:virus interactions with Chikungunya virus. After receiving her B.Tech. in Industrial Biotechnology in 2011, she joined Nanyang Technological University (Singapore) as a PhD student under the supervision of Prof. Chenjie Xu. Her research interest lies in the area of smart nanomaterials for drug delivery and imaging. Current work focuses on the facile synthesis of gold nanoparticles containing liposomes for drug delivery and photoacoustic imaging.

Chenjie Xu is an assistant professor at Nanyang Technological University. He is interested in the development of patientfriendly and efficacious nanotechnologies for drug delivery. The key in this process is to address the unmet need in the drug administration with innovative strategies that can be quickly translated from bench to bedside. Currently, his laboratory is interested in developing nanotechnologies for the targeted drug delivery in the most common diseases like cancer and scar formation.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mathiyazhakan, M., Upputuri, P.K., Sivasubramanian, K. et al. In situ synthesis of gold nanostars within liposomes for controlled drug release and photoacoustic imaging. Sci. China Mater. 59, 892–900 (2016). https://doi.org/10.1007/s40843-016-5101-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40843-016-5101-3

Keywords

Search

Navigation