Heavy Atom Integration in 2-Hydroxymethylquinoline: A Rational Strategy for Enhanced Two-Photon Absorption-Mediated...

Area of Science:

• Materials Science
• Biomedical Engineering
• Organic Chemistry

Background:

• Two-photon absorption (TPA) offers precise drug delivery with deep tissue penetration and high spatial selectivity.
• Hydroxymethylquinoline (HMQ) derivatives are explored for TPA-based applications.
• Triple-negative breast cancer (TNBC) presents significant therapeutic challenges.

Purpose of the Study:

• To rationally design and synthesize novel HMQ derivatives with enhanced TPA properties.
• To investigate the impact of heavy bromine atom incorporation on TPA efficiency and photostability.
• To evaluate the efficacy of these TPA agents for targeted drug delivery in TNBC models.

Main Methods:

• Rational molecular design and synthesis of bromine-containing HMQ compounds.
• Characterization of TPA properties, including TPA cross-section and photostability.
• In vitro and in vivo evaluation of cellular uptake, nuclear localization, and therapeutic efficacy in TNBC models.

Main Results:

• Synthesized HMQ derivatives with significantly enhanced TPA cross-sections (up to 130 GM) due to bromine incorporation.
• Demonstrated efficient tumor and nuclear targeting in TNBC models.
• Achieved substantial therapeutic efficacy (∼75% cell killing) with minimal off-target effects and improved photostability.

Conclusions:

• Incorporating heavy bromine atoms into the HMQ framework is an effective strategy to enhance TPA properties for drug delivery.
• The developed TPA agents show promise for precise theranostic applications in TNBC.
• This approach provides a blueprint for designing advanced TPA-based drug delivery systems for aggressive cancers.