Event Abstract

Tailoring the pH-induced aggregation behaviors of mixed-charge gold nanoparticles for photothermal therapy

  • 1 Zhejiang University, Polymer Science and Engineering, China

Introduction: The acidic microenvironment of tumor tissues has proven to be one of the major differences from other normal tissues. The near-infrared (NIR) light irradiation of aggregated gold nanoparticles in a tumor acidic pH-induced manner could then provide an effect approach to treat solid tumors with the advantage of minimizing the undesired damage to normal tissues[1][2]. Although it is well known the aggregation of larger nanoparticles will results in better NIR photothermal effect, the preparation of pH-sensitive gold nanoparticles in large sizes remain big challenging due to their worse colloidal stability. In this paper, we introduce a facile way to endow gold nanoparticles(GNPs) especially those large ones with tunable pH-aggregation behaviors by modifying the nanoparticle surface with mixed-charge self-assembly monolayers(SAMs) compromising positively and negatively charged thiol ligands.

Fig 1. Schematic illustration of MC-GNPs aggregation in a tumor acidic pH-induced manner for photothermal cancer therapy.(Adapted with permission.[3] Copyright 2014, American Chemical Society.) 

Materials and Methods: pH-sensitive mixed-charge gold nanoparticles (MC-GNPs) were prepared by modifying the GNPs’ surface with mixed SAMs of weak electrolytic 11-mercaptoundecanoic acid (MUA) and strong electrolytic (10-mercaptodecyl) trimethyl-ammonium bromide (TMA). The influence of nanoparticle size (four different sizes were chosen, that is 15 nm, 21nm, 33nm, 53 nm) and surface ligand composition on the pH-induced aggregation behaviors of MC-GNPs were systematically studied. Finally, four different size MC-GNPs that all responded to tumor acidic pH were prepared and their photothermal therapy efficacy was carefully examined.

Results and Discussion: Four different size MC-GNPs with the same surface ligand composition were prepared to study the influence of nanoparticle size on pH-sensitive aggregation behaviors of MC-GNPs. The MC-GNPs in different sizes showed diverse pH-induced aggregation behaviours. That is, as the nanoparticle size increases, the MC-GNPs will aggregate at a higher pH, and vice versa. Next, the same size MC-GNPs with different surface ligand composition were prepared to study the influence of surface ligand composition on pH-sensitive aggregation behaviors of MC-GNPs. By increasing the proportion of MUA in the SAMs, MC-GNPs which aggregated at lower pH were attained, and the opposite was also true. With proper surface ligand composition, the MC-GNPs in four different sizes that all exhibited aggregation at tumor acidic pH were obtained. Among them, the biggest MC-GNPs showed the most encouraging aggregation-enhanced photothermal efficacy in vitro when they formed aggregates. The mixed-charge self-assembled monolayers were then proved as a facile method to design pH-induced aggregation of large gold nanoparticles for better NIR photothermal cancer therapy.

Conclusion:In summary, we systematically explored the basic law of the pH-induced aggregation of MC-GNPs influenced by nanoparticle size and surface charge composition. Given this, we can synthesize certain size MC-GNPs with desired pH-induced aggregation behaviours. In this study, we prepared four different size MC-GNPs that all respond to tumor acidic pH. The aggregates from the largest MC-GNPs showed the most encouraging photothermal therapy efficacy, which implies that mixed-charge surface modification is a facile way to endow nanoparticles with desired pH-sensitivity to better their therapeutic efficiency, especially for those large size ones.

Financial support from the National Science Fund for Distinguished Young Scholars (51025312), the National Basic Research Program of China (2011CB606203), NSFC-50830106 and 21174126, Open Project of State Key Laboratory of Supramolecular Structure and Materials (SKLSSM 201204), and Research Fund for the Doctoral Program of Higher Education of China (20110101110037, 20110101120049, and 20120101130013) is gratefully acknowledged.

References:
[1] J. Nam, N. Won, H. Jin, H. Chung, S. Kim, J. Am. Chem. Soc. 2009, 131, 13639.
[2] X. Liu, Y. Chen, H. Li, N. Huang, Q. Jin, K. Ren, J. Ji, ACS Nano 2013, 7: 6244.
[3] H. Li, X. Liu, H. Nan, K. Ren, Q. Jin, J. Ji, ACS Appl. Mater. Interfaces 2014, 6, 18930

Keywords: Surface modification, Smart material, stimuli-response

Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.

Presentation Type: Poster

Topic: Bioconjugates

Citation: Li H, Liu X, Huang N, Ren K, Jin Q and Ji J (2016). Tailoring the pH-induced aggregation behaviors of mixed-charge gold nanoparticles for photothermal therapy. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.01767

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Received: 27 Mar 2016; Published Online: 30 Mar 2016.

* Correspondence:
Dr. Huan Li, Zhejiang University, Polymer Science and Engineering, Hangzhou, China, Email1
Dr. Xiangsheng Liu, Zhejiang University, Polymer Science and Engineering, Hangzhou, China, Email2
Dr. Nan Huang, Zhejiang University, Polymer Science and Engineering, Hangzhou, China, Email3
Dr. Kefeng Ren, Zhejiang University, Polymer Science and Engineering, Hangzhou, China, Email4
Dr. Qiao Jin, Zhejiang University, Polymer Science and Engineering, Hangzhou, China, Email5
Dr. Jian Ji, Zhejiang University, Polymer Science and Engineering, Hangzhou, China, jijian@zju.edu.cn