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Aptamer-Conjugated Chitosan-Anchored Liposomal Complexes for Targeted Delivery of Erlotinib to EGFR-Mutated Lung Cancer Cells

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Abstract

Lung cancer is the leading cancer and has the highest death rate. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib has had a promising response in lung cancer therapy. Unfortunately, individuals with TKI-resistant EGFR mutations often develop acquired resistance against erlotinib. To overcome this resistance, in the present study, we developed liposomes anchored with anti-EGFR aptamer (Apt)-conjugated chitosan (Apt-Cs) as stable carriers to deliver erlotinib to the target. We loaded erlotinib into Apt-Cs-anchored liposomal complexes (Apt-CL-E) and characterized the physicochemistry of Apt-CL-E. The nanoparticles showed good biostability and a binding specificity for EGFR-mutated cancer cells guided by the Apt. The specific binding facilitated the uptake of Apt-CL-E into EGFR-mutated cancer cells. A cytotoxicity study showed an advantage of Apt-CL-E over their nontargeted liposomal counterparts in delivering erlotinib to EGFR-mutated cancer cells, resulting in cell cycle arrest and apoptosis. These results provide a good platform for future in vivo animal studies with Apt-CL-E.

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Acknowledgments

This work was supported by the Ministry of Science and Technology of China (2015CB931804), the Natural Science Foundation of China (U150520007, 81571802, and 81273548), the Natural Science Foundation of Fujian Province (2016J06020), and the Fujian Development and Reform Commission (2014/168).

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Authors and Affiliations

  1. Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, 2 Xueyuan Road, Yangguang Building, 6FL., Fuzhou, 350002, Fujian, China

    Fengqiao Li, Hao Mei, Xiaodong Xie, Huijuan Zhang, Jian Liu, Tingting Lv, Huifang Nie, Yu Gao & Lee Jia

  2. Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China

    Fengqiao Li, Hao Mei, Xiaodong Xie, Huijuan Zhang, Jian Liu, Tingting Lv, Huifang Nie, Yu Gao & Lee Jia

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  1. Fengqiao Li
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  2. Hao Mei
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  3. Xiaodong Xie
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  4. Huijuan Zhang
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  8. Yu Gao
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Correspondence to Yu Gao or Lee Jia.

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Li, F., Mei, H., Xie, X. et al. Aptamer-Conjugated Chitosan-Anchored Liposomal Complexes for Targeted Delivery of Erlotinib to EGFR-Mutated Lung Cancer Cells. AAPS J 19, 814–826 (2017). https://doi.org/10.1208/s12248-017-0057-9

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