Light-Triggered Concomitant Enhancement of Magnetic Resonance Imaging Contrast Performance and Drug Release Rate of Functionalized Amphiphilic Diblock Copolymer Micelles

Abstract

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 Gd(3+) 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 Gd(3+) complexes was subjected to a transition from being hydrophobic to hydrophilic, leading to the enhancement of MR imaging contrast performance, that is, ~1.9-fold increase in longitudinal relaxivity (r(1)). 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 coenhancement of MR imaging contrast performance and drug release profiles represents a general route to the construction of next generation smart polymeric theranostic nanocarriers.