Light-Switchable
Yolk–Mesoporous Shell UCNPs@MgSiO3 for Nitric Oxide-Evoked
Multidrug Resistance Reversal in
Cancer Therapy
Posted on 2020-06-28 - 18:13
Gas therapy has emerged as a forceful
strategy for augmenting the
effects of chemotherapeutic drugs against cancer cells. However, it
remains extremely challenging to effectively deliver gas into tissues
of interest and unravel its underlying mechanisms. Herein, we designed
a near-infrared (NIR) light-switchable nitric oxide (NO) delivery
nanosystem for high-efficacy multidrug resistance (MDR) reversal in
cancer therapy based on a yolk–shell upconverting nanoparticles@magnesium
silica (UCNP@MgSiO3). The internal hollow cavity and flower-like
mesoporous shell of UCNPs@MgSiO3 not only enabled a significantly
high encapsulation capacity for the NO precursor (BNN6) and doxorubicin
(DOX) but also allowed the enhanced cellular uptake, resulting in
NIR-triggered NO generation and low pH-triggered DOX release in cancer
cells. Mechanistically, intracellular NO can downregulate the drug
efflux-related P-glycoprotein and adenosine 5′-triphosphate-binding
cassette transporters, thereby increasing the DOX accumulation in
the cell nuclei. Such combination therapy of NO and DOX induced the
apoptosis of MDR cells and completely inhibited in vivo MDR tumor
growth. We further elucidated the therapy mechanism via proteomic
profiling, showcasing the downregulation of the ubiquitin–proteasome
pathway and nuclear factor kappa-B signaling pathway in the NO-treated
MDR cells. Therefore, our findings develop a promising nanoscale gas/drug
delivery paradigm for fighting MDR tumors and providing molecular
insights into cancer therapy.
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Li, Shihua; Song, Xiaorong; Zhu, Wei; Chen, Yongling; Zhu, Rong; Wang, Liping; et al. (2020). Light-Switchable
Yolk–Mesoporous Shell UCNPs@MgSiO3 for Nitric Oxide-Evoked
Multidrug Resistance Reversal in
Cancer Therapy. ACS Publications. Collection. https://doi.org/10.1021/acsami.0c06102