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Three-in-One Self-assembled Nanocarrier for Dual-Drug Delivery, Two-Photon Imaging, and Chemo-Photodynamic Synergistic Therapy.

Research paper by Gang-Gang GG Yang, Liang L Hao, Qian Q Cao, Hang H Zhang, Jing J Yang, Liang-Nian LN Ji, Zongwan Z Mao

Indexed on: 01 Aug '18Published on: 01 Aug '18Published in: ACS Applied Materials & Interfaces



Abstract

We herein present a three-in-one nanoplatform (named as Fu/LD@RuCD) for dual-drug delivery, two-photon imaging, and chemo-photodynamic synergistic therapy, enabled by simple self-assembly between adamantine-functionalized ruthenium complexes ([Ru(phen-ad)3](PF6)2, Ru) and natural cyclodextrin (β-CD) monomers. By host-guest chemistry, nanocarrier RuCD 70-90 nm in diameter is fabricated through very simple mixing step in water at room temperature, in which the octahedral configuration of Ru complex provides a rigid skeleton and the hydrogen bonding of secondary hydroxyl groups formed between two adjacent β-CD monomers displays a bridging role allowing for three-dimensional architectures. The dual-drug loaded nanoparticle Fu/LD@RuCD (Fu: 5-fluorouracil; LD: lonidamine) effectively penetrates into cancer cells in 8 h and selectively accumulates in lysosomes, in which dual-drug release is promoted by the mildly acidic environment. Under visible light irradiation, nanocarrier RuCD exhibits excellent PDT capability by producing sufficient ROS and damaging lysosomes, accordingly 5-fluorouracil and lonidamine can escape from lysosomes and reach their sites of action, resulting in mitochondria dysfunction and cancer cell apoptosis. Simultaneously, the excellent photophysical properties of the nanocarrier enables the facile track of drug delivery under one-photon and two-photon excitation. Moreover, in vivo anti-cancer investigations show that Fu/LD@RuCD can effectively inhibit the tumor growth without systemic side effects by chemo-photodynamic synergistic therapy, and the therapeutic effect is better than the free anti-cancer drugs and the sole therapeutic modality.