Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 9, Issue 4, Pages 3294-3305Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.6b11438
Keywords
nanohybrids; NIR fluorescence; OFF-ON; tumor imaging; microRNA modulation therapy
Funding
- National Natural Science Foundation [NSFC31440059, NSFC81272453]
- Innovative Teams and Teacher Career Development for Universities and Colleges Under Beijing Municipality [IDHT20140504]
- Beijing Advanced Innovation Center for Structural Biology (ICSB)
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Theranostic nanoparticles with combined imaging and therapy functions show great promise in cancer precision medicine. In this study, we constructed near-infrared (NIR) OFF-ON fluorescent nanohybrids (F-PNDs) for synchronous tumor imaging and microRNA (miRNA) modulation therapy against esophageal cancer. Nanodiamond clusters (NDs) were first functionalized for protamine sulfate immobilization (PNDs) on their surfaces via a noncovalent self-assembling approach and simultaneous encapsulation of NIR emitting fluorescence dye cyanine 5 (Cy-5) (F-PNDs). Tumor suppressor miRNA-203 (miR-203) was then adsorbed onto the surface of F-PNDs to form miR-203/F-PNDs via electrostatic interactions. The size, morphology, photophysical and stability properties of miR-203/F-PNDs were analyzed. We found that the NIR fluorescence of miR-203/F-PNDs could be activated to the ON state in intracellular environment while remaining in the OFF state in extracellular or blood environment. Furthermore, in vivo live imaging experiments showed that miR-203/F-PNDs could be predominantly accumulated in tumor tissues and image the tumor sites 24 h postintravenous injection. In addition, intravenous and intratumoral injection of miR-203/F-PNDs could efficiently inhibit tumor growth through down-regulation of the expressions of oncogenes Ran and Delta p63. Our study indicated that miRNA/F-PNDs could serve as a promising theranostic platform for synchronous tumor imaging and miRNA-based modulation therapy against cancer.
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