Molecular Motion in Aggregates: Manipulating TICT for Boosting Photothermal Theranostics

Area of Science:

• Materials Science
• Nanotechnology
• Biomedical Engineering

Background:

• Planar donor-acceptor (D-A) structures are standard for photothermal theranostic agents, aiming to restrict intramolecular motion.
• Existing D-A structures may face limitations in non-radiative decay pathways.
• The development of advanced theranostic agents requires overcoming these limitations.

Purpose of the Study:

• To propose an alternative strategy for enhancing photothermal properties by utilizing molecular motion in aggregates.
• To design and synthesize novel small molecules with grafted molecular rotors and bulky alkyl chains.
• To evaluate the efficacy of these new agents for photoacoustic imaging and photothermal therapy.

Main Methods:

• Grafting molecular rotors and bulky alkyl chains onto a central D-A core to reduce intermolecular interactions.
• Synthesizing small molecules (NIRb14, NIRb6, NIR6) with varying alkyl chain structures.
• Utilizing nanoparticles for enhanced photothermal properties and targeted delivery.
• Conducting in vitro and in vivo experiments for efficacy assessment.
• Employing charge-reversal poly(β-amino ester) for specific tumor accumulation.

Main Results:

• Small-molecule NIRb14 with long, branched alkyl chains showed significantly enhanced photothermal properties compared to NIRb6, NIR6, and gold nanorods.
• Enhanced molecular motion favored the formation of a dark twisted intramolecular charge transfer state, boosting non-radiative decay.
• NIRb14 nanoparticles proved effective as nanoagents for photoacoustic imaging-guided photothermal therapy.
• Charge-reversal poly(β-amino ester) facilitated specific accumulation of NIRb14 at tumor sites.

Conclusions:

• An "abnormal" strategy leveraging molecular motion in aggregates can lead to efficient photothermal theranostic agents.
• NIRb14 represents a promising candidate for advanced photoacoustic imaging and photothermal therapy applications.
• This research opens new avenues for designing next-generation theranostic agents through controlled molecular dynamics.