title: Aptamer-Conjugated Chitosan-Anchored Liposomal Complexes for Targeted Delivery of Erlotinib to EGFR-Mutated Lung Cancer Cells.
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.
authors.affiliation: 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.|Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Fengqiao
authors.initials: F
authors.lastname: Li
authors.affiliation: 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.|Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Mei
authors.affiliation: 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.|Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xie
authors.affiliation: 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.|Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 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.|Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: 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.|Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Lv
authors.affiliation: 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.|Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Nie
authors.affiliation: 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. hellogaoyu@126.com.|Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China. hellogaoyu@126.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.affiliation: 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. pharmlink@gmail.com.|Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China. pharmlink@gmail.com.
authors.forename: Lee
authors.initials: L
authors.lastname: Jia
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D052157:Aptamers, Nucleotide / Q000737:chemistry; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage*; D006801:Humans; D008081:Liposomes / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D008081:Liposomes; D048271:Chitosan; D000069347:Erlotinib Hydrochloride
keywords: EGFR-mutated lung cancer; TDDS; aptamer; liposomal complexes; stability