Theranostics 2019; 9(7):1893-1908. doi:10.7150/thno.30523

Research Paper

Tumor Chemo-Radiotherapy with Rod-Shaped and Spherical Gold Nano Probes: Shape and Active Targeting Both Matter

Lu Zhang1, Huilan Su2, Haolu Wang3, Qian Li1, Xiao Li4, Chuanqing Zhou1, Jia Xu1, Yimin Chai1, Xiaowen Liang3✉, Liqin Xiong1, Chunfu Zhang1,5✉

1. Shanghai Jiao Tong University Affiliated 6th Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
2. State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
3. The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia
4. Department of Nuclear Medicine, Changhai Hospital, The Secondary Military Medical University, Shanghai 200433, China
5. Department of Nuclear Medicine, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China

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Citation:
Zhang L, Su H, Wang H, Li Q, Li X, Zhou C, Xu J, Chai Y, Liang X, Xiong L, Zhang C. Tumor Chemo-Radiotherapy with Rod-Shaped and Spherical Gold Nano Probes: Shape and Active Targeting Both Matter. Theranostics 2019; 9(7):1893-1908. doi:10.7150/thno.30523. Available from https://www.thno.org/v09p1893.htm

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Abstract

The morphologies of gold nanoparticles (NPs) affect their tumor accumulation through enhanced permeability and retention effect. However, detailed information and mechanisms of NPs' characteristics affecting tumor accumulation are limited. The aim of this study is to evaluate the effects of shape and active targeting ligands of theranostic NPs on tumor accumulation and therapeutic efficacy, and to elucidate the underlying mechanism.

Methods: αvβ3 integrin-targeted, cisplatin-loaded and radioisotope iodine-125 labeled spherical and rod-shaped gold nano theranostic probes (RGD-125IPt-AuNPs and RGD-125IPt-AuNRs) with similar sizes were fabricated and characterized. The in vivo distribution and chemo-radio therapeutic efficacy against tumors of these newly developed probes were subsequently evaluated. Moreover, a physiologically based pharmacokinetic (PBPK) model was developed to characterize the in vivo kinetics of these probes at the sub-organ level, and to reveal the mechanism of NPs' shape and active targeting ligands effects on tumor accumulation.

Result: Cisplatin and iodine-125 were loaded sequentially onto the NPs through a thin polydopamine coating layer on the NPs. Both RGD-125IPt-AuNPs and RGD-125IPt-AuNRs exhibited high specificity for αvβ3 in vitro, with the rod-shaped probe being more efficient. The PBPK model revealed that rod-shaped gold NPs diffused more rapidly in tumor interstitial than the spherical ones. Tumor accumulations of non-targeted and rod-shaped RAD-125IPt-AuNRs was higher in short term (1 h post injection), but not pronounced and similar to that of non-targeted spherical RAD-125IPt-AuNPs in 24 h after intravenous injection, revealing that the NPs' shape did not have a significant impact on tumor accumulations through enhanced permeability and retention (EPR) effect in long-term. While for actively targeted NPs, in addition to a higher distribution coefficient, RGD-125IPt-AuNRs also had a much higher tumor maximum uptake rate constant than RGD-125IPt-AuNPs, indicating both the shape and active targeting ligands affected the tumor uptake of rod-shaped NPs. As a result, RGD-125IPt-AuNRs had a more effective inhibition of tumor growth than RGD-125IPt-AuNPs by chemo-radiationtherapy.

Conclusion: Our study suggests that both the shape and active targeting ligands of gold NPs play important roles on tumor accumulation and chemo-radio therapeutic effect.

Keywords: gold nanoparticles, chemoradiotherapy, PBPK, SPECT/CT, angiogenesis targeting