Journal
BIOMACROMOLECULES
Volume 13, Issue 11, Pages 3877-3886Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bm301425j
Keywords
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Funding
- National Natural Scientific Foundation of China (NNSFC) [51033005, 91027026, 21274137]
- Fundamental Research Funds for the Central Universities
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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 hydro, phobic-hydrophilic transition within micellar cores and the concomitant enhancement of magnetic resonance (MR) imaging contrast performance, and release, fate, of physically,. encapsulated hydrophobic drugs. POEGMA-b-P(NIPAM-co-NBA-co-Gd) diblock copolymer covalently labeled with Gd3+ (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 was subjected to a transition from being hydrophobic to hydrophilic, leading to the enhancement of MR imaging contrast performance, that is similar to 1.9-fold increase, in longitudinal relaxivity (r(1)). In addition, the release rate of encapsulated Dox was also enhanced (similar to 65% of Dox release in 12 h upon UV irradiation versus similar to 47% Dox release in 25 h for the control). The reported strategy of light triggered coenhancement of MR imaging contrast performance and drug release profiles represents a general route to the construction of next generation smart polymeric theranostic nanocarriers.
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