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Issue 4, 2019
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Ultralong circulating choline phosphate liposomal nanomedicines for cascaded chemo-radiotherapy

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Abstract

Cancer radiation therapy (RT) is limited by endogenous DNA repair of tumor cells and microenvironmental hypoxia in tumor tissues. Herein, we demonstrated an effective cancer chemo-radiotherapy strategy based on choline phosphate liposomal nanomedicines, which inhibit the intrinsic radioresistance of RT and concomitantly harness the RT-induced hypoxia to produce additional toxicity to overcome post-RT radioresistance. To achieve this strategy, a radiotherapy sensitizer, vorinostat, and a hypoxia-activated banoxantrone dihydrochloride (AQ4N) were simultaneously delivered to a tumor using liposomes composed of an inverted polarity lipid 2-((2,3-bis(oleoyloxy)propyl)dimethylammonio)ethyl ethyl phosphate (DOCPe). The DOCPe liposomes exhibited a longer blood circulation time and enhanced tumor accumulation, compared to their zwitterionic phosphocholine counterpart. The RT was sensitized by vorinostat to kill non-tolerant normoxic tumor cells efficiently. The irradiation aggravated hypoxia-activated AQ4N to further potentiate RT treatment. This chemo-radiotherapy combination showed excellent tumor treatment efficacy and is promising for future clinical translation.

Graphical abstract: Ultralong circulating choline phosphate liposomal nanomedicines for cascaded chemo-radiotherapy

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Publication details

The article was received on 10 Jan 2019, accepted on 13 Feb 2019 and first published on 14 Feb 2019


Article type: Paper
DOI: 10.1039/C9BM00051H
Biomater. Sci., 2019,7, 1335-1344

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    Ultralong circulating choline phosphate liposomal nanomedicines for cascaded chemo-radiotherapy

    X. Li, Y. Zhao, W. Jiang, S. Li, M. Zhan, H. Liu, C. Zhang, H. Liang, H. Liu, L. Lu and Y. Wang, Biomater. Sci., 2019, 7, 1335
    DOI: 10.1039/C9BM00051H

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