Journal
ACS NANO
Volume 15, Issue 12, Pages 19793-19805Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.1c07241
Keywords
photosensitizer; nanoscale framework; phototoxicity inhibition; therapeutical activation; cancer therapy
Categories
Funding
- National Natural Science Foundation of China [51972056, 51773036, 52002061]
- Shanghai Shuguang Program [18SG29]
- Program of Shanghai Academic/Technology Research Leader [20XD1420200]
- Major Science and Technology Innovation Project of Shandong Province [2019JZZY011108]
- China Postdocoral Science Foundation [2020M670945]
- Innovation Program of Shanghai Municipal Education Commission [2017-01-07-00-03-E00055]
- Fundamental Research Funds for the Central Universities
- DHU Distinguished Young Professor Program
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The study introduces a strategy to convert double-edged sword PSs into single-edged knife ones, achieving efficient inhibition of tumors, as well as persistent and high phototoxicity inhibition.
The phototoxicity of photosensitizers (PSs) is a double-edged sword with one edge beneficial for destroying tumors while the other is detrimental to normal tissues, and the conventional OFF-ON strategy provides temporary inhibition so that phototoxicity would come sooner or later due to the inevitable retention and transformation of PSs in vivo. We herein put forward a strategy to convert double-edged sword PSs into single-edged knife ones with simultaneously persistent phototoxicity inhibition and alternative multiple therapeutical activation. The Chlorin e6 (Ce6) as the PS model directly assembles with Cu2+ ions into nanoscale frameworks (nFs) whose Cu2+-coordination includes both carboxyl groups and a porphyrin ring of Ce6 instead of Fe3+/Mn2+-coordination with only carboxyl groups. Compared to the high phototoxicity of Ce6, the nFs exhibit efficient energy transfer due to the dual-coordination of paramagnetic Cu2+ ions and the aggregation, achieving the persistent and high phototoxicity inhibition rate of >92%. Alternatively, the nFs not only activate a high photoacoustic contrast and near-infrared (NIR)-driven photothermal efficacy (3.5-fold that of free Ce6) due to the aggregation-enhanced nonradiative transition but also initiate tumor microenvironment modulation, structure disassembly, and chemodynamic effect by Cu2+ ions. Given these merits, the nFs achieve long-term biosecurity, no retina injury under sunlight, and a higher therapeutical output than the photodynamic effect of Ce6. This work presents a possibility of converting numerous highly phototoxic porphyrins into safe and efficient ones.
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