title: ATB0,+transporter-mediated targeting delivery to human lung cancer cells via aspartate-modified docetaxel-loading stealth liposomes.
abstract: Tumor cells have an increased demand for amino acids to support their rapid growth and malignant metastasis. Transfer of amino acids across plasma membranes depends on several amino acid transporters that are highly upregulated in tumor cells and are promising targets for tumor cell-selective therapy. In this study, stealth liposomal systems functionalized with aspartate-polyoxyethylene stearate conjugate (APS) were developed for transporter-mediated targeted delivery to ATB0,+, which is overexpressed human lung cells. The resultant ATB0,+-targeting liposomes (APS-Lips) consisted of a liposome core and the surface coverage of the APS modifier had an optimized density of 10%. APS-Lips had a uniform particle size distribution and high encapsulation efficiency of docetaxel (DTX, >80%). APS modification had a negligible effect on the DTX release from liposomes. Compared with Taxotere and unmodified liposomes, APS-Lips showed increased intracellular delivery and antitumor potency against human lung cells. Furthermore, competitive endocytosis studies showed that the cellular uptake of APS-Lips was notably decreased in the presence of glycine, a typical substrate of ATB0,+, and was increased through adhesion to the cell membrane via transporter-substrate interactions. Finally, in vitro hemolysis and in vivo vascular irritation studies in rabbits confirmed the good blood compatibility and minimal vascular stimulation of the synthetic ATB0,+-targeting material APS. These results demonstrated that the aspartate-modified liposomes could be a promising nanocarrier for ATB0,+transporter-mediated targeted drug delivery to treat lung cancer.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. sunjin66@21cn.com chexin98@aliyun.com and Department of Pharmacy, the First Affiliated Hospital of China Medical University, Shenyang, China and School of Pharmaceutical Science, China Medical University, Shenyang 110122, China.
authors.forename: Qiuhua
authors.initials: Q
authors.lastname: Luo
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. sunjin66@21cn.com chexin98@aliyun.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. sunjin66@21cn.com chexin98@aliyun.com.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Tao
authors.affiliation: College of life science and biological pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. sunjin66@21cn.com chexin98@aliyun.com.
authors.forename: Longfa
authors.initials: L
authors.lastname: Kou
authors.affiliation: Department of Biomedical Engineering, School of Medical Devices, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: He
authors.initials: H
authors.lastname: Lian
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. sunjin66@21cn.com chexin98@aliyun.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Che
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. sunjin66@21cn.com chexin98@aliyun.com.
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. sunjin66@21cn.com chexin98@aliyun.com and Municipal Key Laboratory of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
mesh_terms: D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001224:Aspartic Acid / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018613:Microscopy, Confocal; D015394:Molecular Structure; D043823:Taxoids / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D000970:Antineoplastic Agents; D008081:Liposomes; C503995:SLC6A14 protein, human; D043823:Taxoids; D000077143:Docetaxel; D001224:Aspartic Acid