ngr-peptide and Colorectal-Neoplasms

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.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Survival; Cell-Penetrating Peptides; Chemistry, Pharmaceutical; Colorectal Neoplasms; Dose-Response Relationship, Drug; Drug Carriers; Drug Stability; Female; Half-Life; Humans; Infrared Rays; Injections, Intravenous; Lipids; Male; MCF-7 Cells; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Nanotechnology; Oligopeptides; Paclitaxel; Particle Size; Photons; Rats, Sprague-Dawley; Solubility; Technology, Pharmaceutical; Xenograft Model Antitumor Assays

The objective of this study was to develop and apply cyclic Asn-Gly-Arg (cNGR)-labeled paramagnetic quantum dots (cNGR-pQDs) for the noninvasive assessment of tumor angiogenic activity using quantitative in vivo molecular magnetic resonance imaging (MRI). cNGR was previously shown to colocalize with CD13, an aminopeptidase that is highly overexpressed on angiogenic tumor endothelium. Because angiogenesis is important for tumor growth and metastatization, its in vivo detection and quantification may allow objective diagnosis of tumor status and evaluation of treatment response. I.v. injection of cNGR-pQDs in tumor-bearing mice resulted in increased quantitative contrast, comprising increased longitudinal relaxation rate and decreased proton visibility, in the tumor rim but not in tumor core or muscle tissue. This showed that cNGR-pQDs allow in vivo quantification and accurate localization of angiogenic activity. MRI results were validated using ex vivo two-photon laser scanning microscopy (TPLSM), which showed that cNGR-pQDs were primarily located on the surface of tumor endothelial cells and to a lesser extent in the vessel lumen. In contrast, unlabeled pQDs were not or only sparsely detected with both MRI and TPLSM, supporting a high specificity of cNGR-pQDs for angiogenic tumor vasculature.

Topics: Adenocarcinoma; Algorithms; Animals; Binding, Competitive; Colorectal Neoplasms; Contrast Media; Endothelium, Vascular; Humans; Magnetic Resonance Angiography; Male; Mice; Neovascularization, Pathologic; Oligopeptides; Quantum Dots; Tissue Distribution; Transplantation, Heterologous