Molecular Motion in Aggregates: Manipulating TICT for Boosting Photothermal Theranostics

Abstract

Planar donor and acceptor (D–A) conjugated structures are generally believed to be the standard for architecting highly efficient photothermal theranostic agents, in order to restrict intramolecular motions in aggregates (nanoparticles). However, other channels of extra nonradiative decay may be blocked. Now this challenge is addressed by proposing an “abnormal” strategy based on molecular motion in aggregates. Molecular rotors and bulky alkyl chains are grafted to the central D–A core to lower intermolecular interaction. The enhanced molecular motion favors the formation of a dark twisted intramolecular charge transfer state, whose nonradiative decay enhances the photothermal properties. Result shows that small-molecule NIRb14 with long alkyl chains branched at the second carbon exhibits enhanced photothermal properties compared with NIRb6, with short branched chains, and much higher than NIR6, with short linear chains, and the commercial gold nanorods. Both in vitro and in vivo experiments demonstrate that NIRb14 nanoparticles can be used as nanoagents for photoacoustic imaging-guided photothermal therapy. Moreover, charge reversal poly­(β-amino ester) makes NIRb14 specifically accumulate at tumor sites. This study thus provides an excited molecular motion approach toward efficient phototheranostic agents.

Constitutional Isomerization Enables Bright NIR‐II AIEgen for Brain‐Inflammation Imaging

“…The fluorophore with an ortho ‐positioned hexyl unit is denoted as 2TT‐ o C6B, while the hexyl unit located at meta ‐position stands for 2TT‐ m C6B. As reported previously, 2TT‐ m C6B is a good photothermal contrast agent. However, it experiences a severe ACQ problem, suggesting that only twisted TPA rotor is not sufficient to achieve highly emissive fluorophores.…”

“…These strategies open up new avenues for developing a series of high bright NIR‐II fluorophores, of which the optimized one displays fluorescence emission peaked at 1048 nm with a QY of 5.3% in water . Despite long side chains being capable of reducing intermolecular interactions, they are found to also trigger molecular motions in aggregates, whose nonradiative decay spoils fluorescence QY . Therefore, how to efficiently increase the radiative decay presents a significant bottleneck for high bright NIR‐II fluorophores.…”

“…Recently, a photothermal contrast agent, 2TT‐ m C6B ( Figure a) with NIR‐I absorption (≈808 nm) and NIR‐II emission (1064 nm) has received our attention . This molecule is fluorescent in solution but is almost nonemissive in aggregates (dominated nonradiative decay), displaying typical ACQ effect.…”

Regioisomeric BODIPY Benzodithiophene Dyads and Triads with Tunable Red Emission as Ratiometric Temperature and Viscosity Sensors

“…Challenges in the development of ratiometric temperature/viscosity molecular probes for sensing and especially for bioimaging applications include the development of photostable rotors with red emission for deeper tissue penetration and large Stokes shift for minimal autofluorescence . Significant efforts have been ongoing in the development of TICT with large Stokes shift, red emission and that possess ratiometric temperature/viscosity sensing capabilities . Kuimova et al.…”

Advanced Nanotechnology Leading the Way to Multimodal Imaging‐Guided Precision Surgical Therapy

“…Traditional LN mapping techniques in clinical applications include radionuclide, blue dyes, and fluorescence imaging. 2019, 31,1904329 Passive targeting via EPR effect -PDFT1032 LN mapping and biopsy, osteosarcoma imaging and IGS [31] -SNPs LN mapping [32] -PDI NPs LN mapping and biopsy, glioblastoma imaging and PTT guidance [33] -AGL AIE dots Peritoneal carcinomatosis imaging and IGS [34] -HLZ-BTED dots Breast tumor imaging and visualizing tumor feeding blood vessels [35] -L897 NPs LN and glioblastoma imaging [36] -BPN-BBTD NPs Bladder tumor imaging and PTT guidance [37] Active targeting via ligands Peptide FSH β receptor DCNP-L 1 -FSH β Ovarian cancer imaging and IGS [38] Integrin α v β 3 IR-BEMC6P@RGD Gastroenteropancreatic neuroendocrine tumor imaging and IGS [39] T-TTD dots a) Cholangiocarcinoma imaging and PDT guidance [40] T-TPETS nanodots b) Hepatocellular carcinoma, imaging and PDT guidance [41] 68 Indocyanine green (ICG) is the only near-infrared fluorescence (NIRF) agent approved for clinical application by the Food and Drug Administration (FDA); it is widely used in ophthalmic angiography, the measurement of circulatory system and liver functions, and studies on intraoperative tumor imaging and LN mapping for various cancers, such as head and neck, [59] breast, [60] lung, gastrointestinal, [61] and urologic cancer. [55,56] The combination of two methods with a radionuclide and a dye has been the gold standard for SLN detection.…”