Abstract
The therapeutic effect of reactive oxygen species (ROS)-involved cancer therapies is significantly limited by shortage of oxy-substrates, such as hypoxia in photodynamic therapy (PDT) and insufficient hydrogen peroxide (H2O2) in chemodynamic therapy (CDT). Here, we report a H2O2/O2 self-supplying nanoagent, (MSNs@CaO2-ICG)@LA, which consists of manganese silicate (MSN)-supported calcium peroxide (CaO2) and indocyanine green (ICG) with further surface modification of phase-change material lauric acid (LA). Under laser irradiation, ICG simultaneously generates singlet oxygen and emits heat to melt the LA. The exposed CaO2 reacts with water to produce O2 and H2O2 for hypoxia-relieved ICG-mediated PDT and H2O2-supplying MSN-based CDT, acting as an open source strategy for ROS production. Additionally, the MSNs-induced glutathione depletion protects ROS from scavenging, termed reduce expenditure. This open source and reduce expenditure strategy is effective in inhibiting tumor growth both in vitro and in vivo, and significantly improves ROS generation efficiency from multi-level for ROS-involved cancer therapies.
Highlights
The therapeutic effect of reactive oxygen species (ROS)-involved cancer therapies is significantly limited by shortage of oxy-substrates, such as hypoxia in photodynamic therapy (PDT) and insufficient hydrogen peroxide (H2O2) in chemodynamic therapy (CDT)
The CaO2 NPs were assembled onto the surface of manganese silicate nanoparticles (MSNs) to form MSNs@CaO2 NPs in methanol through electrostatic adsorption, confirmed by the transmission electron microscope (TEM) images (Fig. 2a) and X-ray diffraction (XRD) pattern with the characteristic peaks belong to MSNs and CaO2, respectively (Fig. 2b)
The successful assembly of MSNs@CaO2 was validated by the X-ray photo-electron spectroscopy (XPS) analysis (Supplementary Figure 2a), and the high resolution XPS revealed that the O 2 s existed primarily in the form of silicate and peroxo groups (Supplementary Figure 2b), and the Mn 2p3/2 mainly consisted of 34.65% Mn2+ (641 eV), 55.74% Mn3+ (642 eV), and 9.61% Mn4+ (644 eV) (Fig. 2c)[11,16]
Summary
The therapeutic effect of reactive oxygen species (ROS)-involved cancer therapies is significantly limited by shortage of oxy-substrates, such as hypoxia in photodynamic therapy (PDT) and insufficient hydrogen peroxide (H2O2) in chemodynamic therapy (CDT). The MSNs-induced glutathione depletion protects ROS from scavenging, termed reduce expenditure This open source and reduce expenditure strategy is effective in inhibiting tumor growth both in vitro and in vivo, and significantly improves ROS generation efficiency from multi-level for ROS-involved cancer therapies. Cancer cells are more sensitive to further enhanced oxidative stress beyond the cellular tolerability threshold[2] On this basis, ROS-mediated therapies, such as photodynamic therapy (PDT)[3,4,5,6] and chemodynamic therapy (CDT)[7,8,9,10,11], are developed to disrupt the cellular self-adaptation mechanisms and induce cell death based on ROS-generating agents[12].
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