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Self-Assembly Mitochondria-Targeting Donor-Acceptor Type Theranostic Nanosphere Activates ROS Storm for Multimodal

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Researchers developed novel theranostic agents, TPA-N-, that target mitochondria and induce cancer cell death without external light activation. These agents show superior anticancer performance through multimodal synergistic therapy, highlighting a promising mitochondria-targeting strategy.

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aggregation-induced emissiondonor−acceptor structuremitochondria-targetingmultimodal cancer therapyself-assembly theranostic nanosphere

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Area of Science:

  • Biomedical Engineering
  • Materials Science
  • Oncology

Background:

  • Designing effective cancer theranostics is challenging, especially those combining diagnostic and therapeutic functions without external stimuli.
  • Current theranostics often rely on external triggers like photoirradiation, limiting their clinical applicability.

Purpose of the Study:

  • To design and synthesize novel theranostic agents (TPA-N-) capable of autonomous activation and enhanced anticancer efficacy.
  • To investigate the mechanism of action, focusing on mitochondrial targeting and multimodal synergistic therapy.

Main Methods:

  • Synthesis and characterization of a series of TPA-N- theranostic agents.
  • Evaluation of cytotoxicity, cellular uptake, and reactive oxygen species (ROS) generation in HeLa cancer cells.
  • Assessment of in vivo antiproliferative performance and mechanism of action, including mitophagy and DNA damage response.

Main Results:

  • TPA-N- agents accumulated at tumor sites over 48 hours, demonstrating significant in vivo antiproliferative effects.
  • TPA-N-8 exhibited potent cytotoxicity against HeLa cells (IC50 = 4.3 μM) and self-assembled into nanospheres.
  • TPA-N-8 generated ROS in mitochondria without photoirradiation, triggering PINK1-mediated mitophagy and DNA damage-induced necroptosis and autophagy.

Conclusions:

  • The developed TPA-N- agents represent a successful D-A type theranostic platform for cancer treatment.
  • Mitochondrial targeting and intrinsic ROS generation are effective strategies for achieving multimodal synergistic therapy and superior anticancer outcomes.