Abstract 4528: Folate receptor targeted iron oxide nanoparticles loaded with cisplatin for imaging and therapy in head and neck squamous cell carcinoma (HNSCC).
Authors: Kang Hyunseok , Huang Jing , Peng Xianghong , Chen Zhuo (Georgia) , Mao Hui , Shin Dong M. 
Published: August 2014

Background

Cisplatin (DDP) is a widely used anticancer drug but its application is limited by side effects. We have previously shown that selective delivery of DDP to tumors using novel nanoparticles could significantly enhance antitumor effects with reduced toxicity. Since our group has shown that 45% of 105 HNSCC primary tumors are positive for folate receptor (FR) in Head Neck 31:475-81, 2009, we further developed DDP-loaded folate-targeted iron oxide nanoparticles (FA-IO-DDP) for HNSCC imaging and therapy.

Methods

HNSCC cell lines were screened for FR expression by Western blot analysis and its surface expression was confirmed by FACS. Intracellular platinum (Pt) and Pt-DNA adducts were quantified by ICP-mass spectrometry. MRI was used to detect T2 signal changes induced by iron oxide. Near infrared dye (Cy-5.5) conjugated nanoparticles were used to assess accumulation of the nanoparticles in the tumor tissues and cells. Efficacy and toxicity were assessed using nude mice bearing FR expressing SQCCY1 xenograft using 1mg/kg of free DDP and IO-DDP and FA-IO-DDP equivalent to 0.3mg/kg of free DDP.

Results

Five HNSCC cell lines expressing surface FR were identified among 16 HNSCC cell lines screened. Intracellular Pt and Pt-DNA adducts were increased in FR-positive PCI15B cells treated with FA-IO-DDP by 1.6-fold and 3.8-fold, respectively, compared to cells treated with non-targeted IO-DDP and free DDP (p&lt;0.05). A similar degree of enhanced uptake was observed in FR-expressing SQCCY1 cells but not in FR-negative Tu212 cells. In a subcutaneous SQCCY1 xenograft model in nude mice, tumor targeted FA-IO-DDP showed significantly enhanced efficacy compared to free DDP (p&lt;0.05). Nanoparticles had better efficacy compared to free drug even at lower concentration. The average tumor volume in the FA-IO-DDP treated group was 243.0±412.4 mm3 compared to 541.4±744.5 mm3 and 3324.6±501.3 mm3 in the IO-DDP and free DDP groups, respectively. A notable change in T2 signal in MRI and infrared signal in optical imaging was detected in nude mice bearing SQCCY1 cells 24 hours after treatment with FA-IO-DDP.

Conclusion

Our study showed that novel FR-IO-DDP nanoparticles remarkably enhanced the antitumor effects of DDP in vivo in nude mice bearing FR-positive HNSCC cells and can accumulate in FR-expressing tumors in vivo as detected by MRI and near infrared imaging. Results from the in vitro studies suggest that the effect is mediated by increased intracellular Pt concentration and Pt-DNA adducts. Further analyses in tissues from xenograft mice are ongoing.

This work was supported by Chester Rochfort Endowment Fund/Winship Cancer Institute of Emory University and NIH U01CA151802-02, 1R01CA154846-01 and 1U01CA151810-02.

Citation Format: Hyunseok Kang, Jing Huang, Xianghong Peng, Zhuo (Georgia) Chen, Hui Mao, Dong M. Shin. Folate receptor targeted iron oxide nanoparticles loaded with cisplatin for imaging and therapy in head and neck squamous cell carcinoma (HNSCC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4528. doi:10.1158/1538-7445.AM2013-4528