Smart Nano-Reactors for pH-Responsive Tumor Homing, Mitochondria-Targeting, and Enhanced Photodynamic- Immunotherapy of Cancer
Guangbao Yang1, Ligeng Xu1, Jun Xu1, Rui Zhang1, Guosheng Song1, Yu Chao1, Liangzhu Feng1, Fengxuan Han2, Ziliang Dong1, Bin Li2*, Zhuang Liu1*
1Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren’ai Road, Suzhou, 215123, Jiangsu, China.
2Orthopaedic Institute, Medical College, Soochow University, Suzhou, Jiangsu, China.
Photodynamic therapy (PDT) is an oxygen-dependent light-triggered non-invasive 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). Secondly, as oxygen is critical for PDT-induced cancer destruction, overcoming hypoxia existing in 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 nano-reactors. Such nanoparticles with pH responsive surface coating show enhanced retention responding 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 nano-reactors 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 non-irradiated tumors 1-2 cm away, promising for metastasis inhibition.