title: Photolabile-caged peptide-conjugated liposomes for siRNA delivery.
abstract: Light is an ideal general triggered signal, which occurs as a result of its non-invasive nature, desirable controllability and high spatial resolution. However, due to its low penetrability and ability to harm tissues, the use of ultraviolet (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. In this study, we have devised and tested a strategy for site-specific delivery of small interfering RNA (siRNA) into cancer cells by using liposomes bearing a photolabile-caged peptide (PCP). The positive charges of the lysine residues on the cell-penetrating peptide (CPP) were temporarily caged by the NIR two-photon excitation-responsive protective groups (PG), thereby forming a PCP. Once illuminated by NIR light at tumor tissues, these PGs were cleaved; the positively charged CPP regained its activity and facilitated rapid intracellular delivery of the liposomes into cancer cells. The PCP was connected with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine via a polyethylene glycol (PEG) spacer to prepare the modified liposomes (PCP-LP). Subsequent research demonstrated that the application of the PCP modifications may provide an approach for the selectively targeted delivery of siRNA.
authors: a Beijing Institute of Pharmacology and Toxicology , Beijing , China .|b Wuhan General Hospital of Guangzhou Military Command , Wuhan , China , and.
authors: XiangYang
authors: X
authors: Xie
authors: a Beijing Institute of Pharmacology and Toxicology , Beijing , China .|c Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation , Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China.
authors: YanFang
authors: Y
authors: Yang
authors: a Beijing Institute of Pharmacology and Toxicology , Beijing , China .
authors: Yang
authors: Y
authors: Yang
authors: a Beijing Institute of Pharmacology and Toxicology , Beijing , China .
authors: XingGuo
authors: X
authors: Mei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001682:Biological Availability; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000096:biosynthesis; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D007259:Infrared Rays; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry* / Q000528:radiation effects*; D061986:MCF-7 Cells; D008297:Male; D015282:Octreotide / Q000031:analogs & derivatives* / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats
chemical_list: C576034:1,2-distearoylglycero-3-phosphoethanolamine-N-(methoxy(polyethylene glycol)-2000)octreotate; D057846:Cell-Penetrating Peptides; D008081:Liposomes; D010714:Phosphatidylethanolamines; D034741:RNA, Small Interfering; C512478:EGFR protein, human; D066246:ErbB Receptors; D015282:Octreotide
keywords: Cancer; drug delivery; liposomes; near-infrared two-photon photolysis; photolabile-caged peptide; small interfering RNA