title: Photo-responsive and NGR-mediated multifunctional nanostructured lipid carrier for tumor-specific therapy.
abstract: A novel nanostructured lipid carrier (NLC) modified with photon-sensitive cell penetrating peptides (psCPP) and Asn-Gly-Arg (NGR) was designed to enhance paclitaxel (PTX)-targeted delivery and antitumor effect. The NGR moiety selectively binds to CD13-positive tumors. On other hand, the psCPP moiety enhance specific cancer cellular uptake after rapidly cleaving the two-photon excitation-responsive protective group, in this case, illumination in the presence of near-IR (NIR) light at the tumor site. The dual-modified NLC (psCPP/NGR-NLC) were prepared by emulsification method, and the concentrations of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol 2000-psCPP (DSPE-PEG2000 -psCPP) and DSPE-PEG5000 -NGR in the NLC were chosen to be 4% and 1% (molar ratio), respectively. The mean particle size of the psCPP/NGR-NLC was about 100 nm, and the drug entrapment efficiency was more than 90%. Stability study showed that the prepared NLCs were physically and chemically stable at 2°C-8°C up to 1 month. Cellular uptake results demonstrated that the proposed psCPP/NGR-NLC had an enhancement of cancer cell recognition and specific uptake. Pharmacokinetic study showed that the prepared psCPP/NGR-NLC possessed the long-circulation characteristic with the t1/2 of 6.112 ± 0.304 h. Pharmacodynamics results confirmed that, with the aid of NIR illumination and NGR, the tumor inhibition ratio of psCPP/NGR-NLC group was significantly higher than the other PTX groups.
authors: Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China; Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical college, Beijing, 100050, China.
authors: Yanfang
authors: Y
authors: Yang
authors: Xiangyang
authors: X
authors: Xie
authors: Yang
authors: Y
authors: Yang
authors: Hui
authors: H
authors: Zhang
authors: Xingguo
authors: X
authors: Mei
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000528:radiation effects*; D002626:Chemistry, Pharmaceutical; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004355:Drug Stability; D005260:Female; D006207:Half-Life; D006801:Humans; D007259:Infrared Rays; D007275:Injections, Intravenous; D008055:Lipids / Q000737:chemistry*; D061986:MCF-7 Cells; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles; D036103:Nanotechnology; D009842:Oligopeptides / Q000737:chemistry / Q000528:radiation effects*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D010316:Particle Size; D017785:Photons; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D008055:Lipids; C526428:NGR peptide; D009842:Oligopeptides; D017239:Paclitaxel
keywords: NGR-targeted; cancer chemotherapy; light activation; lipids; nanoparticles; peptides; targeted drug delivery