title: Human cytotoxic T-lymphocyte membrane-camouflaged nanoparticles combined with low-dose irradiation: a new approach to enhance drug targeting in gastric cancer.
abstract: Cell membrane-derived nanoparticles are becoming more attractive because of their ability to mimic many features of their source cells. This study reports on a biomimetic delivery platform based on human cytotoxic T-lymphocyte membranes. In this system, the surface of poly-lactic-co-glycolic acid nanoparticles was camouflaged using T-lymphocyte membranes, and local low-dose irradiation (LDI) was used as a chemoattractant for nanoparticle targeting. The T-lymphocyte membrane coating was verified using dynamic light scattering, transmission electron microscopy, and confocal laser scanning microscopy. This new platform reduced nanoparticle phagocytosis by macrophages to 23.99% (P=0.002). Systemic administration of paclitaxel-loaded T-lymphocyte membrane-coated nanoparticles inhibited the growth of human gastric cancer by 56.68% in Balb/c nude mice. Application of LDI at the tumor site significantly increased the tumor growth inhibition rate to 88.50%, and two mice achieved complete remission. Furthermore, LDI could upregulate the expression of adhesion molecules in tumor vessels, which is important in the process of leukocyte adhesion and might contribute to the localization of T-lymphocyte membrane-encapsulated nanoparticles in tumors. Therefore, this new drug-delivery platform retained both the long circulation time and tumor site accumulation ability of human cytotoxic T lymphocytes, while local LDI could significantly enhance tumor localization.
authors.affiliation: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Lianru
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Rutian
authors.initials: R
authors.lastname: Li
authors.affiliation: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wei
authors.affiliation: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Hanqing
authors.initials: H
authors.lastname: Qian
authors.affiliation: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Shu
authors.initials: S
authors.lastname: Su
authors.affiliation: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shao
authors.affiliation: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Wang
authors.affiliation: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Qian
authors.affiliation: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Baorui
authors.initials: B
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D016503:Drug Delivery Systems; D006801:Humans; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000737:chemistry; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use; D010587:Phagocytosis / Q000187:drug effects; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000528:radiation effects*
chemical_list: D000970:Antineoplastic Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017239:Paclitaxel
keywords: cell membrane; drug delivery system; gastric cancer; low-dose irradiation; nanoparticles