Mei Zhou,Boying Li,Ning Li,Mengying Li,Chengfen Xing
Ca2+ overload is caused by the abnormal accumulation of Ca2+, which is a potential therapeutic strategy for inhibiting tumor growth. However, due to the limited intracellular Ca2+ concentration, its anticancer effect is non-significant. Herein, near-infrared (NIR)-responsive nanoparticles NPs-PCa (DPPC-DSPE-PEG2000-NH2@PDPP@CaO2@DOX) were designed and prepared to achieve photothermal trigger of Ca2+ release, thereby increasing intracellular Ca2+ content. Furthermore, the nanoparticles convert light to heat to activate the transient receptor potential cation channel subfamily V member 1 (TRPV1) ion channels, allowing external Ca2+ to flow into the cells, further increasing the Ca2+ concentration. NPs-PCa nanoparticles overcome the limitation of insufficient concentration by increasing Ca2+ in both internal and external approaches. Meanwhile, an imbalance of intracellular Ca2+ induces mitochondrial dysfunction and ultimately results in cancer cell death. This study provides an effective strategy for inhibiting breast cancer tumor growth by regulating Ca2+ concentration.
Jie Shen,Huizhu Yu,Yimeng Shu,Ming Ma,Hangrong Chen
The efficacy of cancer therapy with reactive oxygen species (ROS) as the main therapeutic medium suffers from a deficiency of oxy-substrates, for example, insufficient endogenous hydrogen peroxide (H 2 O 2 ) in chemodynamic therapy (CDT) and inherent hypoxia in photodynamic therapy (PDT). Herein, a smart polyethylene glycol (PEG)-ylated nanosystem CaO 2 @ZIF-Fe/Ce6@PEG (abbreviation as CaZFCP) is constructed to achieve H 2 O 2 /O 2 self-supply and Ca 2+ overloading in tumor cells simultaneously for enhanced CDT/PDT. Under the weakly acidic tumor microenvironment, the activity components inside CaZFCP, that is, CaO 2 nanoparticles, Fe 2+ , and photosensitizer Chlorin e6 (Ce6) are released by the degradation of zeolitic imidazole framework-90 (ZIF-90). Thereinto, CaO 2 nanoparticles are further decomposed to generate H 2 O 2 and O 2 , which alleviates both the insufficient endogenous H 2 O 2 and hypoxia in tumor area, thus enhancing the efficiency of CDT and PDT by producing more hydroxyl radicals and singlet oxygen. Furthermore, Ca 2+ overloading induced by the decomposition of CaO 2 is available for amplifying intracellular oxidative stress, resulting in mitochondrial dysfunction, which further improves the efficacy of combined CDT/PDT. In vitro and in vivo experimental results confirm excellent tumor inhibition effect, which also provides a facile paradigm in ROS-involved cancer therapies.
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