Photodynamic therapy (
PDT) is an
oxygen-dependent light-triggered noninvasive therapeutic method showing many promising aspects in
cancer treatment. For effective
PDT, nanoscale carriers are often needed to realize
tumor-targeted delivery of
photosensitizers, which ideally should further target specific cell organelles that are most vulnerable to
reactive oxygen species (ROS). Second, as
oxygen is critical for
PDT-induced
cancer destruction, overcoming
hypoxia existing in the majority of solid
tumors is important for optimizing
PDT efficacy. Furthermore, as
PDT is a localized treatment method, achieving systemic antitumor therapeutic outcomes with
PDT would have tremendous clinical values. Aiming at addressing the above challenges, we design a unique type of
enzyme-encapsulated,
photosensitizer-loaded hollow
silica nanoparticles with rationally designed surface engineering as smart nanoreactors. Such nanoparticles with pH responsive surface coating show enhanced retention responding to the acidic tumor microenvironment and are able to further target mitochondria, the cellular organelle most sensitive to ROS. Meanwhile, decomposition of
tumor endogenous H2O2 triggered by those nanoreactors would lead to greatly relieved tumor hypoxia, further favoring in vivo
PDT. Moreover, by combining our nanoparticle-based
PDT with check-point-blockade
therapy, systemic antitumor immune responses could be achieved to kill nonirradiated
tumors 1-2 cm away, promising for
metastasis inhibition.