title: iRGD-coupled responsive fluorescent nanogel for targeted drug delivery.
abstract: In this investigation, we have designed and synthesized a multifunctional nanogel for anti-tumor drug delivery. Thermo- and pH-responsive poly (N-isopropyl acrylamide-co-acrylic acid) nanogels (NGs) were synthesized by free radical precipitation polymerization. Positive charged chemotherapeutic drug doxorubicin (DOX) was introduced into the negatively charged swollen NGs by electrostatic adsorption at pH 7.4. Fluorescent bovine serum albumin (BSA) encapsulated gold nanoclusters (AuNCs) were conjugated onto the surface of NGs, followed by functionalization of tumor targeting peptide iRGD onto the BSA for tumor targeting. Interestingly, the DOX-encapsulated iRGD-decorated NGs maintain both thermo- and pH-responsive properties, which are favorable for achieving a controlled drug release in tumor tissues. Stable red fluorescent emission, derived from AuNCs, was used to detect and track the NGs in vitro. As expected, the iRGD motif mediated specific targeting to tumor and endothelial cells and enhanced cellular uptake of the NGs, as demonstrated by flow cytometry and confocal microscopy assays. In vitro cytotoxicity studies proved that the presence of iRGD enhanced the cytotoxic efficiency of DOX to the targeted cells. All together, our current study indicates that the NGs drug-carriers can deliver chemotherapeutic drug specifically to the tumor and endothelial cells with enhanced anti-tumor efficacy and controlled drug release.
authors: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
authors: Shishuai
authors: S
authors: Su
authors: Hai
authors: H
authors: Wang
authors: Xiaoguang
authors: X
authors: Liu
authors: Yan
authors: Y
authors: Wu
authors: Guangjun
authors: G
authors: Nie
mesh_terms: D000818:Animals; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D005453:Fluorescence; D006046:Gold / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D057446:Hydrodynamics; D020128:Inhibitory Concentration 50; D008024:Ligands; D053768:Metal Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D051379:Mice; D000080385:Nanogels; D009842:Oligopeptides / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D012542:Scattering, Radiation; D012710:Serum Albumin, Bovine / Q000378:metabolism; D012996:Solutions; D013057:Spectrum Analysis; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
chemical_list: D008024:Ligands; C569656:N-end cysteine peptide tumor-homing peptide; D000080385:Nanogels; D009842:Oligopeptides; D012996:Solutions; C413692:polyethylene glycol polyethyleneimine nanogel; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D006046:Gold; D004317:Doxorubicin; D011094:Polyethyleneimine