Journal
SMALL
Volume 15, Issue 5, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.201804028
Keywords
deep tissue penetration; imaging-guided theranostics; metalloporphyrin complexes; nanosonosensitizers; noninvasive sonodynamic therapy
Categories
Funding
- Key International S&T Cooperation Project [2015DFH50230]
- National Natural Science Foundation of China [21701033, 81701816, 81501591, 81671758, 31571013, 51502333, 81501580]
- Guangdong Natural Science Foundation of Research Team [2016A030312006]
- Natural Science Foundation of Guangdong Province [2017A030313079, 2017A030313726]
- Dongguan Project on Social Science and Technology Development [2015108101019]
- Shenzhen Science and Technology Program [JSGG20160331185422390, JCYJ20160429191503002]
- Ph.D. Foundation of Guangdong Medical University [B2017016]
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Metal complexes are widely used as anticancer drugs, while the severe side effects of traditional chemotherapy require new therapeutic modalities. Sonodynamic therapy (SDT) provides a significantly noninvasive ultrasound (US) treatment approach by activating sonosensitizers and initiating reactive oxygen species (ROS) to damage malignant tissues. In this work, three metal 4-methylphenylporphyrin (TTP) complexes (MnTTP, ZnTTP, and TiOTTP) are synthesized and encapsulated with human serum albumin (HSA) to form novel nanosonosensitizers. These nanosonosensitizers generate abundant singlet oxygen (O-1(2)) under US irradiation, and importantly show excellent US-activatable abilities with deep-tissue depths up to 11 cm. Compared to ZnTTP-HSA and TiOTTP-HSA, MnTTP-HSA exhibits the strongest ROS-activatable behavior due to the lowest highest occupied molecular orbital-lowest unoccupied molecular orbital gap energy by density functional theory. It is also effective for deep-tissue photoacoustic/magnetic resonance dual-modal imaging to trace the accumulation of nanoparticles in tumors. Moreover, MnTTP-HSA intriguingly achieves high SDT efficiency for simultaneously suppressing the growth of bilateral tumors away from ultrasound source in mice. This work develops a deep-tissue imaging-guided SDT strategy through well-defined metalloporphyrin nanocomplexes and paves a new way for highly efficient noninvasive SDT treatments of malignant tumors.
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