Journal
RSC ADVANCES
Volume 9, Issue 68, Pages 39924-39931Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c9ra08142a
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Funding
- Natural Science Foundation of China [61775037, 61805041]
- Bethune Aishikun Surgical Excellence Fund
- Joint Funds for the Innovation of Science and Technology, Fujian province [2018Y9119]
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Designing tumor microenvironment (TME)-specific active nanoparticles with minimum side effects for synergistic cancer therapy has become a hot topic in the recent decades. Aiming at further enhancing the therapeutic efficacy, an in situ-induced mitochondrial dysfunction is a very promising strategy. To achieve these goals, a nano-sono-chemodynamic agent denoted as TPP-Cu@HMS, which integrated hematoporphyrin monomethyl ether (HMME), mPEG-NHS, triphenylphosphonium (TPP)-decorated mesoporous silica (MS) and coordinatively bound Cu2+ ions for mitochondria-specific sonodynamic-chemodynamic therapy (SDT-CDT) of cancer, was designed. Upon the ultrasound (US) treatment, TPP-Cu@HMS can specifically target mitochondria and in situ generate O-1(2) against cancer cells. Specifically, to overcome the short lifespan of O-1(2), the released Cu2+ ions from TPP-Cu@HMS could act as a Fenton-like agent to convert endogenous H2O2 to center dot OH in the acidic environment of cancer cells, disrupt the mitochondrial membrane potential and lead to mitochondrial disintegration, which could systematically enhance the therapeutic efficiency of SDT. Therefore, we highlight the current strategy as a promising prospect for cancer therapy.
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