Main content area

Redox/ATP switchable theranostic nanoparticles for real-time fluorescence monitoring of doxorubicin delivery

Lin, Yi, Yang, Yidi, Yan, Jianqin, Chen, Jun, Cao, Jun, Pu, Yuji, Li, Li, He, Bin
Journal of materials chemistry 2018 v.6 no.14 pp. 2089-2103
antineoplastic activity, apoptosis, chemical bonding, complementary DNA, cytotoxicity, deoxyribonucleases, doxorubicin, fluorescence, fluorescent dyes, monitoring, nanoparticles, neoplasm cells, neoplasms, oligonucleotides, physiological transport, polyethylene glycol
In this study, redox/ATP switchable theranostic nanoparticles (TNs) with precise specificity and controllable mobility were developed for the real-time monitoring of the release of an anticancer drug. A fluorescent probe (FAM) and a quencher (BHQ-1) were covalently conjugated to one end of an adenosine-5′-triphosphate (ATP) aptamer and its complementary DNA (cDNA), respectively. Then, doxorubicin (DOX) was intercalated within the DNA duplex to form a stable physical conjugate (FBA@DOX). Poly(ethylene glycol)-block-poly (aspartic acid-graft-cystamine) (PAS), a glutathione-sensitive cationic polymer, was synthesized and complexed with the FBA@DOX, endowing it with excellent stability in physiological solutions. Fluorescence recovery/quenching, DNase degradation, in vitro drug release, cellular uptake, and intracellular trafficking results revealed that the TNs remained in the “OFF” state, with a minimal FAM fluorescent signal and negligible DOX premature release, in low-glutathione and/or low-ATP environments. In contrast, the TNs turned “ON” and rapidly released FBA@DOX in glutathione-rich environments after internalization in cancer cells. The intracellular ATP triggered the conformational changes in FBA@DOX, thereby enabling the controlled release of DOX and simultaneous recovery of the fluorescence for monitoring the DOX release. In a cytotoxicity and apoptosis study, the redox/ATP switchable TNs demonstrated strong anticancer effects, attributable to their selective release of the drug. Overall, our findings may offer a promising strategy for developing a new generation of “smart” theranostic platforms.