title: Active targeting docetaxel-PLA nanoparticles eradicate circulating lung cancer stem-like cells and inhibit liver metastasis.
abstract: Lung cancer is the major cause of cancer related lethality worldwide, and metastasis to distant organs is the pivotal cause of death for the vast majority of lung cancer patients. Accumulated evidence indicates that lung cancer stem-like cells (CSLCs) play important roles in metastagenesis, and these circulating CSLCs may be important targets to inhibit the subsequent metastasis. The present study was aimed at establishing CSLC-targeting polylactic acid (PLA) encapsulated docetaxel nanoparticles for antimetastatic therapy. Cyclic binding peptides were screened on CSLCs in vitro and the peptide CVKTPAQSC exhibiting high specific binding ability to pulmonary adenocarcinoma tissue was subsequently conjugated to the nanoparticles loaded with docetaxel (NDTX). Antimetastatic effect of CSLC-targeting nanoparticles loaded with docetaxel (TNDTX) was evaluated in a nude mouse model of liver metastasis. Results showed that, in the absence of targeting peptide, NDTX hardly exhibited any antimetastatic effect. However, TNDTX treatment significantly decreased the metastatic tumor area in the nude mouse liver. Histopathological and serological results also confirmed the antimetastatic efficacy of TNDTX. To our knowledge, this is the first report on establishing a CSLC-based strategy for lung cancer metastatic treatment, and we hope this will offer a potential therapeutic approach for management of metastatic lung cancer.
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College , 100005, Beijing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.forename: Yao
authors.initials: Y
authors.lastname: Jiang
authors.forename: Huifeng
authors.initials: H
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.forename: Chunying
authors.initials: C
authors.lastname: Hou
authors.forename: Ji
authors.initials: J
authors.lastname: Zheng
authors.forename: Yanyong
authors.initials: Y
authors.lastname: Liu
authors.forename: Pingping
authors.initials: P
authors.lastname: Zuo
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001835:Body Weight; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004337:Drug Carriers; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000187:drug effects*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D043823:Taxoids / Q000008:administration & dosage*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; D004337:Drug Carriers; D006023:Glycoproteins; D010455:Peptides; D011091:Polyesters; D011108:Polymers; C000606024:Prom1 protein, mouse; D043823:Taxoids; D000077143:Docetaxel; D019344:Lactic Acid; C033616:poly(lactide)
keywords: CD133; cancer stem-like cells (CSLCs); lung cancer; metastasis; nanoparticles; targeting therapy