Yu Cai

Acute kidney injury (AKI) is a clinical syndrome primarily attributed to mitochondrial dysfunction, characterized by disrupted mitochondrial balance. Impaired biogenesis leads to insufficient energy supply, while defective autophagy results in the accumulation of damaged mitochondria‐both of which exacerbate injury to renal tubular epithelial cells. In this study, we developed melatonin/pioglitazone liposomes (MP@Lip) for AKI therapy via restoration of mitochondrial dynamic balance. When melatonin and pioglitazone was jointly delivered to damaged renal tubules, they activated mitochondrial autophagy and biogenesis, thereby bidirectionally restoring mitochondrial network homeostasis. Mechanistically, AMPK/SIRT3/PGC‐1α‐related signaling may be involved in the mitochondrial protection of MP@Lip. Upon AMPK phosphorylation, SIRT1/SIRT3 deacetylase activity is upregulated, the ratio of LC3B‐II/LC3B‐I increases, p62/SQSTM1 decreases, and autophagy is enhanced. PGC‐1α enhances transcriptional activity and promotes the expression of mitochondrial biogenic markers (TOM20). This complementary degradation‐synthesis loop gradually restores mitochondrial dynamic balance. In vitro experiments confirmed that MP@Lip reduces ROS production and apoptosis while restoring mitochondrial membrane potential. In vivo studies demonstrated improvement in renal function indicators, alleviation of inflammatory responses and histopathological damage, and no systemic toxicity. This strategy shifts AKI treatment from symptomatic support to ameliorating mitochondrial dysfunction, providing a targeted, complementary and relatively safe approach that may be applicable to other mitochondrial functional‐related diseases.

Photoacoustic imaging (PAI) as an innovative biomedical imaging modality shows high contrast and superior spatial resolution, yet remains limited by underdeveloped second near-infrared (NIR-II, 1000-1700 nm) contrast agents, particularly neglecting the NIR-IIb (1500-1700 nm) window. In this work, we designed a new class of diimmonium (DB)-based dicationic nano-agents (DB·2X, X = TFSI ^- , B(C ₂ O ₄ ) ₂ ^- , or BF ₄ ^- ) for 1700 nm excitation PAI. Density functional theory (DFT) calculations reveal that dicationic DB ²⁺ exhibits a dramatically reduced excitation energy (1.24 eV) and enhanced oscillator strength (f = 1.11) by molecular engineering, attributed to a symmetry-allowed local excitation mechanism for electronic restructuring. Single-crystal X-ray diffraction further demonstrates the intermolecular spacings >5.0 Å in DB·2X aggregates, facilitating optimized non-radiative transitions for amplified PAI signals. In vivo study using different disease models shows that DB·2TFSI nano-agents under 1700 nm excitation can achieve higher signal-to-background ratio and minimized interference from endogenous chromophores compared to conventional 1064 nm excitation. Biocompatibility assessments confirm low cytotoxicity, underscoring potential for further development of DB·2TFSI nano-agents. This work delivers a robust molecular design paradigm for non-radiative decay optimization, and for the first time establishes 1700 nm-excitable PAI nano-agents, paving the way for tissue high-quality biomedical imaging.

Sepsis-associated acute kidney injury (SA-AKI) is a critical complication in intensive care units (ICUs) with a high mortality rate, and current treatments

The development of high-performance organic photothermal conversion agents (PTCAs) with strong near-infrared (NIR) absorption, high photothermal conversion efficiency (PCE), and excellent biocompatibility remains a critical challenge in photothermal therapy (PTT). In this study, we designed and synthesized a series of novel donor-acceptor-donor (D-A-D) small molecules based on a benzo[1,2-b:4,3-b']dithiophene-4,5-dione (BDTD-4,5-dione) core as a strong electron-accepting unit, symmetrically functionalized with triphenylamine (TPA) derivatives as tunable electron donors. By focusing on the strong electron-donating N,N-dimethylaniline (NPA) unit-contrasted with a methoxy-substituted analog-we achieved effective modulation of the HOMO energy, bandgap, and supramolecular aggregation, underscoring the advantage of enhanced donor strength for photothermal applications. Spectroscopic and electrochemical analyses revealed that electron-rich substituents significantly redshifted the intramolecular charge transfer (ICT) absorption into the NIR region (650-900 nm) and enhanced molar extinction coefficients. Among the derivatives, the dimethylamino-functionalized compound (BDQ-NPA) exhibited the most redshifted absorption, a narrow bandgap (2.0 eV), and an outstanding PCE of 35.05% under 808 nm laser irradiation. Theoretical calculations confirmed strong D-A interactions and efficient charge separation in the excited state. BDQ-NPA self-assembled into stable nanoparticles with excellent photostability and biocompatibility, facilitating efficient cellular uptake and NIR-triggered photothermal ablation of cancer cells in vitro. In vivo studies demonstrated significant tumor growth inhibition in a murine model following a single dose of BDQ-NPA and 808 nm irradiation, with no observable systemic toxicity. This work establishes BDTD-4,5-dione as a promising acceptor core for NIR-absorbing organic PTCAs and highlights the efficacy of substituent engineering in optimizing photothermal performance for cancer theranostics.