Journal
JOURNAL OF MATERIALS CHEMISTRY B
Volume 3, Issue 14, Pages 2786-2800Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5tb00070j
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Funding
- National Natural Science Foundation of China [21174096, 21274100, 21234005]
- Specialized Research Fund for the Doctoral Program of Higher Education [20123201130001]
- Project of Science and Technology Development Planning of Suzhou [ZXG201413, SYG201430]
- Project of Science and Technology Development Planning of Jiangsu Province [BK20141192]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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Optical imaging of tumors is of great significance to increase the survival rate of cancer patients due to its apparent advantages in terms of the simplicity of implementation, high sensitivity, avoiding the use of radioactive irradiation, low running cost and the ability to allow for real-time monitoring. Compared with the traditional fluorescent sensor detection model, this work developed a novel strategy to fabricate multifunctional nanoparticles (NPs) with pH-activatable near-infrared (NIR) fluorescence and magnetism imaging abilities via activators generated by electron transfer for surface-initiated atom transfer radical polymerization (SI-AGET ATRP) on the surface of silica coated iron oxide (Fe3O4@SiO2) NPs and subsequent surface modification with NIR pH-activatable benzo[a] phenoxazine dyes. Particularly, the pH-activated NIR fluorescent NPs based on benzo[a] phenoxazine (3b) have negligible fluorescence above pH 7.0 but display significant fluorescence enhancement and discernible color change below pH 6.0, with a pK(a) of 5.6. Cellular microscopy studies demonstrated that the attachment of the pH-sensitive dye to silica coated iron oxide NPs facilitated the NIR fluorescence enhancement of the as-prepared MNPs in tumor cells (4T1 and 293T) under acidic conditions. A satisfactory tumor-to-normal tissue signal ratio (T/N ratio) and a prolonged time-window for 4T1 tumor visualization were observed in vivo, where tumors were evident within 3 h post-injection and maintained for at least 24 h. Therefore, this strategy provides a fluorescent/magnetic iron oxide NPs prototype to visualize the solid tumor in vivo by sensing the tumor acidic microenvironment with minimal systemic toxicity.
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