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SCIENCE CHINA Materials, Volume 59, Issue 11: 892-900(2016) https://doi.org/10.1007/s40843-016-5101-3

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

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  • ReceivedJul 18, 2016
  • AcceptedAug 29, 2016
  • PublishedOct 8, 2016

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 nm within 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.


Acknowledgment

The work was partially supported by NTU-Northwestern Institute for Nanomedicine (To Xu CJ), the Tier-2 Grant funded by the Ministry 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 appreciate Mr. Stanley Sim Siong Wei to help us draw the illustration.


Interest statement

The authors declare that they have no conflict of interest.


Contributions statement

Mathiyazhakan M and Xu C conceived the project and wrote the manuscript. Mathiyazhakan M and Upputuri PK performed the cell culture, liposome synthesis and experiments. Upputuri PK, Sivasubramanian K, Pu K and Pramanik M assisted and provided constructive input for NIR laser stimulation experiments. Dhayani A, Vemula PK, Zou P and Yang C performed and provided inputs on TEM analysis. The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.


Author 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 patient-friendly 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.


Supplement

Supplementary information

Supplementary data are available in the online version of the paper.


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  • Figure 1

    Characterization of AuNS-liposomes: (a) UV spectrum of plain liposomes (dotted line) and AuNS-liposome complex (solid line). (b) TEM image of AuNS-liposomes. Scale bar: 50 nm; (c) HRTEM image of AuNSs collected from AuNS-liposomes. Scale bar: 50 nm.

  • Scheme 1

    Schematic of the synthesis of AuNS-liposome complex by diffusion controlled method and its use in light-controlled drug release.

  • Figure 2

    AuNS-liposome complex as contrast agents for photoacoustic imaging: (a) photoacoustic spectra of AuNS-liposome complex; (b) photoacoustic signal intensity vs. concentration of AuNS-liposome complex; (c) comparison of photoacoustic signals of 2 mg mL−1 AuNS-liposome complex and fresh mouse blood; (d) comparison of photoacoustic signals of 2 mg mL−1 AuNS-liposome complex and fresh mouse blood under 1-cm deep fresh chicken breast tissue. The excitation laser pulse was at 803 nm in (b–d).

  • Figure 3

    AuNS-liposome complex as the drug carrier for controlled release: (a) UV-vis spectra of Dox-liposomes and Dox-AuNS-liposome complex; (b) release of Dox from the Dox-liposomes and Dox-AuNS-liposome complex under the irradiation of NIR pulse laser. Error bars indicate the standard deviation (SD, N ≥ 3).

  • Figure 4

    Viability of B16-F10 melanoma cells after the treatment with Dox, AuNS-liposomes, Dox-liposomes, and Dox-AuNS-liposomes with or without pulsed laser: (a) Alamar Blue cell viability assay. Error bars indicate the SD (N ≥ 3); (b) live/dead staining assay with calcein acetomethoxy and propidium iodide. Scale bar: 100 µm.

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