title: A near-infrared two-photon-sensitive peptide-mediated liposomal delivery system.
abstract: Tumour-oriented nanocarrier drug delivery approaches with photo-sensitivity have been drawing considerable attention over the years. However, due to its low penetrability and ability to induce tissue damage, the use of UV light for triggered nanocarrier release in in vivo applications has been limited. Compared with UV light, near-infrared (NIR) light deeply penetrates tissues and is less damaging to cells. Here, we report on the development of a novel method employing photo-sensitive cell-penetrating peptides (CPPs), which can be used to trigger the transport of liposomes into cells following stimulation, which was irradiation with NIR light in this case. The positive charges of the lysine residues on the CPP were temporarily caged by a NIR two-photon excitation-responsive protective group (PG), thereby forming photo-sensitive peptides (PSPs). The PSP was connected with DSPE via a polyethylene glycol (PEG) spacer to prepare the modified liposomes (PSP-L). Once illuminated by NIR light in tumour tissues, these PGs were cleaved, and the positively charged CPP regained its activity and facilitated rapid intracellular delivery of the liposomes into cancer cells. The PSP-L carrying vinorelbine bitartrate prepared in this work possessed suitable physiochemical properties. In addition, strong cellular uptake and cytotoxic activity of PSP-L in MCF-7 cells were correlated with NIR illumination. Furthermore, triggered NIR activation of PSP-L led to higher antitumour efficacy in the MCF-7 tumour model in nude mice compared with the unmodified liposomes (N-L). In conclusion, the application of PSP modifications to drug-carrying liposomes may provide an approach for the targeted delivery of antitumour agents.
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: YanFang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China; Wuhan General Hospital of Guangzhou Military Command, Wuhan 430070, China.
authors.forename: XiangYang
authors.initials: X
authors.lastname: Xie
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: XingShi
authors.initials: X
authors.lastname: Cai
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: ZhiYuan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China. Electronic address: amms2013@126.com.
authors.forename: XingGuo
authors.initials: X
authors.lastname: Mei
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000494:pharmacology*; D004339:Drug Compounding; D065546:Drug Liberation; D005260:Female; D006801:Humans; D007259:Infrared Rays; D007275:Injections, Intravenous; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry* / Q000648:ultrastructure; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000077235:Vinorelbine; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D057846:Cell-Penetrating Peptides; D008081:Liposomes; D011838:Radiation-Sensitizing Agents; D011092:Polyethylene Glycols; D014747:Vinblastine; D000077235:Vinorelbine
keywords: Cell-penetrating peptides; Drug delivery; Liposomes; Near-infrared (NIR) two-photon photolysis; Photo-sensitive peptides