title: Matrix metalloproteinase triggered size-shrinkable gelatin-gold fabricated nanoparticles for tumor microenvironment sensitive penetration and diagnosis of glioma.
abstract: To improve glioma targeting delivery efficiency and to monitor drug delivery and treatment outcome, a novel tumor microenvironment sensitive size-shrinkable theranostic system was constructed and evaluated. The G-AuNPs-DC-RRGD system was constructed by fabricating small sized gold nanoparticles (AuNPs) onto matrix metalloproteinase-2 (MMP-2) degradable gelatin nanoparticles (GNPs), doxorubicin (DOX) and Cy5.5 were decorated onto AuNPs through a hydrazone bond to enable the system with pH triggered cargoes release, and RRGD, a tandem peptide of RGD and octarginine was surface-modified onto the system to enable it with glioma active targeting ability. In vitro, the size of G-AuNPs-DC-RRGD could effectively shrink from 188.2 nm to 55.9 nm after incubation with MMP-2, while DOX and Cy5.5 were released in a pH dependent manner. Cellular uptake demonstrated that G-AuNPs-DC-RRGD could be effectively taken up by cells with higher intensity than G-AuNPs-DC-PEG. A study of tumor spheroids further demonstrated that the particles with smaller size showed better penetration ability, while RRGD modification could further improve permeability. In vivo, G-AuNPs-DC-RRGD displayed the best glioma targeting and accumulation efficiency, with good colocalization with neovessels. Cy5.5 also was colocalized well with DOX, indicating that Cy5.5 could be used for imaging of DOX delivery.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China. gaohuile@scu.edu.cn.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Ruan
authors.forename: Qin
authors.initials: Q
authors.lastname: He
authors.forename: Huile
authors.initials: H
authors.lastname: Gao
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000473:pathology; D002232:Carbocyanines / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry*; D005910:Glioma / Q000175:diagnosis* / Q000473:pathology; D006046:Gold / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D010316:Particle Size; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D004337:Drug Carriers; D006046:Gold; D004317:Doxorubicin; D005780:Gelatin; D020778:Matrix Metalloproteinase 2