Macrophage-mediated delivery of light activated nitric oxide prodrugs with spatial, temporal and concentration control

Chemical Science
Michael A EvansSamir Mitragotri

Abstract

Nitric oxide (NO) holds great promise as a treatment for cancer hypoxia, if its concentration and localization can be precisely controlled. Here, we report a "Trojan Horse" strategy to provide the necessary spatial, temporal, and dosage control of such drug-delivery therapies at targeted tissues. Described is a unique package consisting of (1) a manganese-nitrosyl complex, which is a photoactivated NO-releasing moiety (photoNORM), plus Nd3+-doped upconverting nanoparticles (Nd-UCNPs) incorporated into (2) biodegradable polymer microparticles that are taken up by (3) bone-marrow derived murine macrophages. Both the photoNORM [Mn(NO)dpaqNO2 ]BPh4(dpaqNO2 = 2-[N,N-bis(pyridin-2-yl-methyl)]-amino-N'-5-nitro-quinolin-8-yl-acetamido) and the Nd-UCNPs are activated by tissue-penetrating near-infrared (NIR) light at ∼800 nm. Thus, simultaneous therapeutic NO delivery and photoluminescence (PL) imaging can be achieved with a NIR diode laser source. The loaded microparticles are non-toxic to their macrophage hosts in the absence of light. The microparticle-carrying macrophages deeply penetrate into NIH-3T3/4T1 tumor spheroid models, and when the infiltrated spheroids are irradiated with NIR light, NO is released in quantifiable amounts w...Continue Reading

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Citations

Jul 13, 2019·Nanomedicine·Feby Wijaya PratiwiPeilin Chen
Mar 21, 2020·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Nahal HabibiJoerg Lahann
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Feb 11, 2021·Advanced Materials·Jinhua LiZhen Gu
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Apr 7, 2020·The Journal of Physical Chemistry Letters·Hojeong YoonManho Lim
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Oct 30, 2021·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Yun SunHong Yang

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Methods Mentioned

BETA
transmission electron microcopy
protein assay
dynamic light scattering
confocal microscopy
flow cytometry
irradiate
light scattering
PCR
atomic emission spectroscopy

Software Mentioned

ImageJ

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