title: Bioimaging of Intravenous Polymeric Micelles Based on Discrimination of Integral Particles Using an Environment-Responsive Probe.
abstract: One of the biggest challenges in bioimaging of nanoparticles is how to identify integral particles from bulk signals of probes. Signals of free probes are always mistakenly counted into total signals of particles. In this study, in vivo fate of intravenous polymeric micelles (PMs, mPEG2.5k-PDLLA2.5k) was explored using a highly sensitive near-infrared environment-responsive fluorescent probe. This probe is able to emit fluorescence when embedded in nanocarriers but quench spontaneously and absolutely upon release into water, based on the aggregation-caused quenching effect, which means that the interference generated by free probes can be completely diminished. Analysis of blood-borne fluorescence reveals rapid clearance of PMs from blood following a tricompartmental pharmacokinetic model. Live imaging shows pervasive distribution of PMs throughout the body, and a tendency of accumulation to extremities with fluorescence density 3-5 times higher than the trunk. Ex vivo examination reveals that most PMs are found in vital organs following an order of lung > liver > spleen > heart > kidney in concentration, but an order of liver > lung > spleen > heart ≈ kidney in total amount. The distribution to other organs and tissues is even lower, and to brain, negligible. It is concluded that the biodistribution of PMs to vital organs and extremities warns of potential toxicity and can be translated to explain the toxicity of its commercial counterpart with similar chain lengths.
authors.affiliation: School of Pharmacy, Fudan University , Key Laboratory of Smart Drug Delivery of MOE and PLA, Shanghai 201203, China.
authors.forename: Haisheng
authors.initials: H
authors.lastname: He
authors.affiliation: School of Pharmacy, Fudan University , Key Laboratory of Smart Drug Delivery of MOE and PLA, Shanghai 201203, China.|Key Laboratory for Special Functional Materials of the Ministry of Education, Henan University , Kaifeng 475001, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Fudan University , Key Laboratory of Smart Drug Delivery of MOE and PLA, Shanghai 201203, China.
authors.forename: Yunchang
authors.initials: Y
authors.lastname: Xie
authors.affiliation: School of Pharmacy, Fudan University , Key Laboratory of Smart Drug Delivery of MOE and PLA, Shanghai 201203, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: School of Pharmacy, Fudan University , Key Laboratory of Smart Drug Delivery of MOE and PLA, Shanghai 201203, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Qi
authors.affiliation: School of Pharmacy, Fudan University , Key Laboratory of Smart Drug Delivery of MOE and PLA, Shanghai 201203, China.
authors.forename: Ejaj
authors.initials: E
authors.lastname: Ahmad
authors.affiliation: School of Pharmacy, Fudan University , Key Laboratory of Smart Drug Delivery of MOE and PLA, Shanghai 201203, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Dong
authors.affiliation: School of Pharmacy, Fudan University , Key Laboratory of Smart Drug Delivery of MOE and PLA, Shanghai 201203, China.|Key Laboratory for Special Functional Materials of the Ministry of Education, Henan University , Kaifeng 475001, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Fudan University , Key Laboratory of Smart Drug Delivery of MOE and PLA, Shanghai 201203, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D003952:Diagnostic Imaging / Q000379:methods*; D004337:Drug Carriers / Q000737:chemistry; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D011092:Polyethylene Glycols; C033616:poly(lactide)
keywords: PEG−PLA; biodistribution; bioimaging; environment-responsive; fluorescent probes; long-circulating; polymeric micelles; stealth