Journal
ADVANCED MATERIALS
Volume 29, Issue 43, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.201704196
Keywords
cancer theranostics; heptamethine cyanine dyes; mitochondria-targeting agents; near-infrared imaging; phototherapy
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Funding
- National Natural Science Foundation of China [81130026, 81402784]
- State Key Basic Research Development Program [2012CB518103]
- University Innovation Team Building Program of Chongqing [CXTDG201602020]
- Intramural research project [BWS13C016, AWS14007-01, AWS13J002]
- Southwestern Hospital [SWH2016LHJC-06]
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An urgent challenge for imaging-guided disease-targeted multimodal therapy is to develop the appropriate multifunctional agents to meet the requirements for potential applications. Here, a rigid cyclohexenyl substitution in the middle of a polymethine linker and two asymmetrical amphipathic N-alkyl side chains to indocyanine green (ICG) (the only FDA-approved NIR contrast agent) are introduced, and a new analog, IR-DBI, is developed with simultaneous cancer-cell mitochondrial targeting, NIR imaging, and chemo-/PDT/PTT/multimodal therapeutic activities. The asymmetrical and amphipathic structural modification renders IR-DBI a close binding to albumin protein site II to form a drug-protein complex and primarily facilitates its preferential accumulation at tumor sites via the enhanced permeability and retention (EPR) effect. The released IR-DBI dye is further actively taken up by cancer cells through organic-anion-transporting polypeptide transporters, and the lipophilic cationic property leads to its selective accumulation in the mitochondria of cancer cells. Finally, based on the high albumin-binding affinity, IR-DBI is modified into human serum albumin (HSA) via self-assembly to produce a nanosized complex, which exhibits significant improvement in the cancer targeting and multimodal cancer treatment with better biocompatibility. This finding may present a practicable strategy to develop small-molecule-based cancer theranostic agents for simultaneous cancer diagnostics and therapeutics.
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