Multifunctional Platinum(IV) and Cyanine Dye-based Polyprodrug for Trimodal Imaging-Guided Chemo-Phototherapy

Imaging-guided chemo-phototherapy based on a single nanoplatform has a great significance to improve the efficiency of cancer therapy and diagnosis. However, high drugs content, no burst release and real-time tracking...

Tubular J-aggregates of cyanine dyes in the near-infrared

Developing improved organic infrared emitters has wide-ranging applicability in fields such as bioimaging or energy harvesting. We synthesize redshifted analogues of C8S3, a well-known cyanine dye that self assembles into tubular aggregates which have attracted widespread attention as artificial photosynthetic complexes. Despite the elongated dye structure, the new pentamethine dyes retain their tubular self-assembly and emit at near-infrared wavelengths. Cryo-electron microscopy and detailed photophysical characterization of the new aggregates reveal similar absorption lineshapes with ~100 nm of redshift, as well as supramolecular morphologies that resemble their trimethine counterparts; the pentamethine aggregates generally show more disorder and decreased superradiance, suggesting that more ordered structures yield more robust photophysical properties. These results provide design principles of superradiant organic emitters, expand the chemical space of near-infrared aggregates, and introduce two additional wavelength-specific antennae as model systems for study.

Dye-loaded mesoporous polydopamine nanoparticles for multimodal tumor theranostics with enhanced immunogenic cell death

Background Tumor phototherapy especially photodynamic therapy (PDT) or photothermal therapy (PTT), has been considered as an attractive strategy to elicit significant immunogenic cell death (ICD) at an optimal tumor retention of PDT/PTT agents. Heptamethine cyanine dye (IR-780), a promising PDT/PTT agent, which can be used for near-infrared (NIR) fluorescence/photoacoustic (PA) imaging guided tumor phototherapy, however, the strong hydrophobicity, short circulation time, and potential toxicity in vivo hinder its biomedical applications. To address this challenge, we developed mesoporous polydopamine nanoparticles (MPDA) with excellent biocompatibility, PTT efficacy, and PA imaging ability, facilitating an efficient loading and protection of hydrophobic IR-780. Results The IR-780 loaded MPDA (IR-780@MPDA) exhibited high loading capacity of IR-780 (49.7 wt%), good physiological solubility and stability, and reduced toxicity. In vivo NIR fluorescence and PA imaging revealed high tumor accumulation of IR-780@MPDA. Furthermore, the combined PDT/PTT of IR-780@MPDA could induce ICD, triggered immunotherapeutic response to breast tumor by the activation of cytotoxic T cells, resulting in significant suppression of tumor growth in vivo. Conclusion This study demonstrated that the as-developed compact and biocompatible platform could induce combined PDT/PTT and accelerate immune activation via excellent tumor accumulation ability, offering multimodal tumor theranostics with negligible systemic toxicity. Graphical Abstract

Unsymmetrical cyanine dye via in vivo hitchhiking endogenous albumin affords high-performance NIR-II/photoacoustic imaging and photothermal therapy

Herein, an unprecedented synergistic strategy for the development of high-performance NIR-II fluorophore is proposed and validated. Based on an unsymmetrical cyanine dye design strategy, the NIR-II emissive dye NIC was successfully developed by replacing only one of the indoline donors of symmetrical cyanine dye ICG with a fully conjugated benz[c,d]indole donor. This minor structural change maximally maintains the high extinction coefficient advantage of cyanine dyes. NIC-ER with endogenous albumin-hitchhiking capability was constructed to further enhance its in vivo fluorescence brightness. In the presence of HSA (Human serum albumin), NIC-ER spontaneously resides in the albumin pocket, and a brilliant ~89-fold increase in fluorescence was observed. Due to its high molar absorptivity and moderate quantum yield, NIC-ER in HSA exhibits bright NIR-II emission with high photostability and significant Stokes shift (>110 nm). Moreover, NIC-ER was successfully employed for tumor-targeted NIR-II/PA imaging and efficient photothermal tumor elimination. Overall, our strategy may open up a new avenue for designing and constructing high-performance NIR-II fluorophores.

Designing Highly Luminescent Molecular Aggregates via Bottom-Up Nanoscale Engineering

Coupling of excitations between organic fluorophores in J-aggregates leads to coherent delocalization of excitons across multiple molecules, resulting in materials with high extinction coefficients, long-range exciton transport, and, in particular, short radiative lifetimes. Despite these favorable optical properties, uses of J-aggregates as high-speed light sources have been hindered by their low photoluminescence quantum yields. Here, we take a bottom-up approach to design a novel J-aggregate system with a large extinction coefficient, a high quantum yield and a short lifetime. To achieve this goal, we first select a J-aggregating cyanine chromophore and reduce its nonradiative pathways by rigidifying the backbone of the cyanine dye. The resulting conformationally-restrained cyanine dye exhibits strong absorbance at 530 nm and fluorescence at 550 nm with 90% quantum yield and 2.3 ns lifetime. We develop optimal conditions for the self-assembly of highly emissive J-aggregates. Cryogenic transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS) reveal micron-scale extended structures with 2D sheet-like morphology, indicating long-range structural order. These novel J-aggregates have a strong red-shifted absorption at 600 nm, resonant fluorescence with no Stokes shift, 50% quantum yield, and 220 ps lifetime at room temperature. We further stabilize these aggregates in a glassy sugar matrix and study their excitonic behavior using temperature-dependent absorption and fluorescence spectroscopy. These temperature- dependent studies confirm J-type excitonic coupling and superradiance. Our results have implications for the development of a new generation of organic fluorophores that combine high speed, high quantum yield and solution processing.