Multimodal phototherapy agents target lipid droplets for near-infrared imaging-guided type I photodynamic/photothermal therapy.

The construction and optimization of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy (PDT), and photothermal therapy (PTT) functions remain challenging. In this study, we aimed to design and synthesize four donor-acceptor (D-A) type aggregation-induced emission molecules: PSI, TPSI, PSSI, and TPSSI. We employed phenothiazine as an electron donor and 1,3-bis(dicyanomethylidene)indan as a strong electron acceptor in the synthesis process. Among them, TPSSI exhibited efficient type I reactive oxygen species generation, high photothermal conversion efficiency (45.44 %), and near-infrared emission. These observations can be attributed to the introduction of a triphenylamine electron donor group and a thiophene unit, which resulted in increased D-A strengths, a reduced singlet-triplet energy gap, and increased free intramolecular motion. TPSSI was loaded into bovine serum albumin to prepare biocompatible TPSSI nanoparticles (NPs). Our results have indicated that TPSSI NPs can target lipid droplets with negligible dark toxicity and can efficiently generate O2•- in hypoxic tumor environments. Moreover, TPSSI NPs selectively targeted 4T1 tumor tissues and exhibited a good PDT-PTT synergistic effect in vitro and in vivo. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technologies. STATEMENT OF SIGNIFICANCE: The construction of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy, and photothermal therapy functions, and its optimization remain challenging. In this study, we construct four donor-acceptor aggregation-induced emission molecules using phenothiazine as an electron donor and 1,3-Bis(dicyanomethylidene)indan as a strong electron acceptor. By optimizing the molecular structure, an integrated phototherapy agent with fluorescence imaging ability and high photodynamic / photothermal therapy performance was prepared. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technology.

pH and GSH dual-responsive drug-controlled nanomicelles for breast cancer treatment.

We developed a pH/glutathione (GSH) dual-responsive smart nano-drug delivery system to achieve targeted release of a chemotherapeutic drug at breast tumor site. Doxorubicin (DOX) was linked to polyethylene glycol (PEG) through cis-aconitic anhydride (CA) and disulfide bonds (SS) to obtain the PEG-SS-CA-DOX prodrug, which spontaneously assembled into nanomicelles with a particle size of 48 ± 0.45 nm. PEG-SS-CA-DOX micelles achieved an efficient and rapid release of DOX under dual stimulation by weak acidic pH and high GSH content of tumors, with the release amount reaching 88.0% within 48 h. Cellular uptake experiments demonstrated that PEG-SS-CA-DOX micelles could efficiently transport DOX into cells and rapidly release it in the tumor microenvironment. In addition,in vivoantitumor experiments showed that PEG-SS-CA-DOX had a high inhibition rate of 70% against 4T1 breast cancer cells along with good biosafety. In conclusion, dual-responsive smart nanomicelles can achieve tumor-targeted drug delivery and specific drug release, thus improving therapeutic efficacy of drugs.