Journal
ACS NANO
Volume 12, Issue 4, Pages 3780-3795Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b00999
Keywords
sonodynamic therapy; protoporphyrin; nanoenzyme; tumor microenvironment; nanomedicine
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Funding
- National Key RAMP
- D Program of China [2016YFA0203700]
- National Nature Science Foundation of China [51722211, 51672303]
- Natural Science Foundation of Shanghai [13ZR1463500]
- Young Elite Scientist Sponsorship Program by CAST [2015QNRC001]
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Ultrasound (US)-triggered sonodynamic therapy (SDT) can solve the critical issue of low tissue penetrating depth of traditional phototriggered therapies, but the SDT efficacy is still not satisfactorily high in combating cancer at the current stage. Here we report on augmenting the SDT efficacy based on catalytic nano medicine, which takes the efficient catalytic features of nanoenzymes to modulate the tumor microenvironment (TME). The multifunctional nanosonosensitizers have been successfully constructed by the integration of a MnO component with biocompatible/biodegradable hollow mesoporous organosilica nanoparticles, followed by conjugation with protoporphyrin (as the sonosensitizer) and cyclic arginine-glycine-aspartic pentapeptide (as the targeting peptide). The MnO component in the composite nanosonosensitizer acts as an inorganic nanoenzyme for converting the tumor-overexpressed hydrogen peroxide (H2O2) molecules into oxygen and enhancing the tumor oxygen level subsequently, which has been demonstrated to facilitate SDT-induced reactive oxygen species production and enhance SDT efficacy subsequently. The targeted accumulation of these composite nanosonosensitizers efficiently suppressed the growth of U87 tumor xenograft on nude mice after US-triggered SDT treatment. The high in vivo biocompatibility and easy excretion of these multifunctional nanosonosensitizers from the body have also been evaluated and demonstrated to guarantee their future clinical translation, and their TME-responsive T-1-weighted magnetic resonance imaging capability provides the potential for therapeutic guidance and monitoring during SDT.
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