NIR-II fluorophores (1000-1700 nm) are pivotal for biomedical imaging, offering deep-tissue penetration and high signal-to-noise ratios but suffer from low quantum yields (QY < 0.01%) beyond 1200 nm. To date, most reported NIR-II small-molecule dyes are derived from polymethine and xanthene frameworks. However, achieving NIR-II chromophores with sufficient QYs remains challenging, as the energy gap law dictates that internal conversion-governed by the emission energy gap and reorganization energy-dominates nonradiative decay. To address this, we designed a novel pseudo-2D molecular framework: 34 π-electron annulated porphyrinoids (Scheme 1), engineered to minimize reorganization energy. These structures achieve emission wavelengths up to 1290 nm with QYs of 1.10-6.14%. Density functional theory (DFT) calculations were performed to unravel the photophysical mechanisms underlying these behaviors, showing that the reorganization energy is as small as 10.5 meV for these dyes, which validates our design. The optimized molecular structures and the stacking geometry of these porphyrinoids in the nanoparticle form were also elaborated by DFT. The intense NIR-II fluorescence (>1200 nm) enables high-resolution in vivo vascular imaging, further enhanced by AI-driven imaging algorithms to significantly improve image quality.

Peer reviewed article authored by (Steponkiene S, Kavaliauskiene S, Purviniene R, Rotomskis R, Juzenas P). Read article or submit your manuscript for publishing.

Nanoparticles engineered to combat cancer and other life-threatening diseases may significantly improve patient outcomes. However, inefficient nanoparticle delivery to tumors limits their use and necessitates the development of complex delivery approaches. Here, we examine this issue by harnessing the tumor-homing abilities of human mesenchymal stem cells (MSCs) to deliver a decoupled theranostic complex of rare earth-doped nanoparticles (dNPs) and photosensitizer chlorin e6 (Ce6) to tumors. We show that both bone-marrow- and skin-derived MSCs can transport the dNP-Ce6 complex inside tumor spheroids, which is challenging to accomplish by passive delivery alone. MSCs deliver the dNP-Ce6 complex across the tumor spheroid, facilitating more effective photodynamic damage and tumor destruction than passively accumulated dNP-Ce6. The dNP-Ce6 complex also provides the built-in ability to monitor the MSC migration without causing undesired phototoxicity, which is essential for maximal and side-effect-free delivery of nanoparticles. Our results demonstrate how MSCs can be used as delivery vehicles for the transportation of the dNP-Ce6 complex, addressing the limitations of passive nanoparticle delivery and providing light-based theranostics.

Background/Objectives: Meibomian gland dysfunction (MGD) and dry eye syndrome (DES) are common eye diseases characterized by altered tear film stability and inflammation of the ocular surface, causing significant discomfort and possible visual impairment. This study aimed to investigate the efficacy of curcumin-loaded liposomes (Lipo@Cur) compared to cyclosporine A-loaded liposomes (Lipo@CycA) in experimental rabbit models of MGD and DES, with a focus on their ability to improve tear film stability and reduce ocular surface inflammation. Methods: MGD and DES were induced using complete Freund’s adjuvant (CFA) and treated to evaluate the effect of liposomal formulations on tear break-up time (TBUT), clinical signs of inflammation (telangiectasia, conjunctival hyperemia, meibomian foramen occlusion), and corneal as well as conjunctival histological cells. Results: Lipo@Cur increased TBUT and reduced the signs of ocular surface inflammation, potentially approaching the effectiveness of clinically approved cyclosporine A encapsulated in liposomes (Lipo@CycA). Histological analysis suggested improvements in corneal epithelial thickness and goblet cell density in the treated groups, which may indicate a reversal of DES-induced damage to the ocular surface. Conclusions: Plant-originated curcumin encapsulated in liposomes offers a promising therapeutic strategy for the management of MGD and DES that may improve patient outcomes by addressing the underlying inflammatory mechanisms of these conditions.

Fluorescence imaging in the NIR-IIb window (1500–1700 nm) enables unparalleled tissue penetration and contrast, yet efficient organic fluorophores >1500 nm remain extremely scarce due to intrinsic trade-offs between emission wavelength and brightness in symmetric molecular designs. To date, molecular scaffolds predominantly adopt either symmetric planar or twisted frameworks, which can individually optimize the long emission wavelength (λ_em) or high quantum yield (ϕ) but fail to overcome this fundamental optical trade-off simultaneously. In this study, we propose a rational asymmetric design that integrates planar ACQ units with twisted AIE rotors within a single molecular scaffold, uniting the complementary advantages of long λ_em, a high molar extinction coefficient (ε), and elevated ϕ. We further introduce the concept of intermolecular noncovalent conformational locks (NoCLs) that can precisely tune the photophysical properties within nanoparticles. To validate this concept, we design and synthesize a systematic library of asymmetric dyes (T-X-J, T-X-BJ, J-X-BJ, and T-Si-BJ) by combining heteroatom-substituted xanthene cores (O, Si) with structurally diverse electron-donating groups (T, J, BJ), alongside symmetric analogues (T-X-T, J-X-J, BJ-X-BJ, T-Si-T, and BJ-Si-BJ) as controls. Embedding these dyes into a heteroatom-rich polymer matrix (Pttc-TTQ) establishes intermolecular noncovalent conformational locks (C–H···π and C–H···O) for enabling precise regulation of dihedral angles and significantly enhancing ϕ in nanoparticles. Notably, T-Si-BJ exhibits emission >1500 nm in CH₂Cl₂, representing the first asymmetric organic dye with emission maxima in the NIR-IIb window, and demonstrates the brightest (14.1 M^–1 cm^–1) nanoparticles with emission maxima at 1320 nm and tail signal extending into the NIR-IIb region among the reported optical trade-off fluorophores in H₂O (Scheme 1). T-Si-BJ was further prepared as polymer dots (Pdots) for high-contrast, deep-tissue vascular imaging and AI-assisted resolution of hindlimb vasculature. This study provides a synthetically versatile and structurally diverse platform for NIR-IIb fluorophores, demonstrating that asymmetric donor–acceptor–donor scaffolds coupled with polymer-mediated geometry control can simultaneously optimize the emission wavelength and brightness.