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Light-Triggered Concomitant Enhancement of Magnetic Resonance Imaging Contrast Performance and Drug Release Rate of Functionalized Amphiphilic Diblock Copolymer Micelles.
MedLine Citation:
PMID:  23013152     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Polymeric drug nanocarriers integrated with diagnostic and sensing functions are capable of in situ monitoring the biodistribution of chemotherapeutic drugs and imaging/contrasting agents, which enables the establishment of image-guided personalized cancer therapeutic protocols. Responsive multifunctional theranostic nanocarriers possessing external stimuli-tunable drug release rates and imaging signal intensities represent another promising direction in this field. In this work, we fabricated responsive amphiphilic diblock copolymer micelles exhibiting light-triggered hydrophobic- hydrophilic transition within micellar cores and the concomitant enhancement of magnetic resonance (MR) imaging contrast performance and release rate of physically encapsulated hydrophobic drugs. POEGMA-b-P(NIPAM-co-NBA-co-Gd) diblock copolymer covalently labeled with Gd3+ complex (Gd) in the light-responsive block was synthesized at first, where OEGMA, NIPAM, and NBA are oligo(ethylene glycol) monomethyl ether methacrylate, N-isopropylacrylamide, and o-nitrobenzyl acrylate, respectively. The amphiphilic diblock copolymer spontaneously self-assembles in aqueous solution into micellar nanoparticles possessing hydrophobic P(NIPAM-co-NBA-co-Gd) cores and hydrophilic POEGMA coronas, which can physically encapsulate doxorubicin (Dox) as a model chemotherapeutic drug. Upon UV irradiation, hydrophobic NBA moieties within micellar cores transform into hydrophilic carboxyl derivatives, triggering micelle microstructural changes and core swelling. During this process, the microenvironment surrounding Gd3+ complexes were subjected to a transition from being hydrophobic to hydrophilic, leading to the enhancement of MR imaging contrast performance, i.e., ~1.9-fold increase in longitudinal relaxivity (r1). In addition, the release rate of encapsulated Dox was also enhanced (~65% of Dox release in 12 h upon UV irradiation versus ~47% Dox release in 25 h for the control). The reported strategy of light-triggered co-enhancement of MR imaging contrast performance and drug release profiles represents a general route to the construction of next generation smart polymeric theranostic nanocarriers.
Authors:
Yamin Li; Yinfeng Qian; Tao Liu; Guoying Zhang; Shiyong Liu
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-27
Journal Detail:
Title:  Biomacromolecules     Volume:  -     ISSN:  1526-4602     ISO Abbreviation:  Biomacromolecules     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100892849     Medline TA:  Biomacromolecules     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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