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

Author:
Lin, Yi, Yang, Yidi, Yan, Jianqin, Chen, Jun, Cao, Jun, Pu, Yuji, Li, Li, He, Bin
Source:
Journal of materials chemistry 2018 v.6 no.14 pp. 2089-2103
ISSN:
2050-7518
Subject:
antineoplastic activity, apoptosis, chemical bonding, complementary DNA, cytotoxicity, deoxyribonucleases, doxorubicin, fluorescence, fluorescent dyes, monitoring, nanoparticles, neoplasm cells, neoplasms, oligonucleotides, physiological transport, polyethylene glycol
Abstract:
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.
Agid:
6185635