Complexes formed by combining pentacyclic triterpenes (PTs) with Aggregation-Induced Emission luminogens (AIEgens), termed pentacyclic triterpene-aggregation induced emission (PT-AIEgen) complexes, merge the chemotherapeutic properties of PTs with the photocytotoxicity of AIEgens. In this study, we synthesized derivatives by connecting three types of triphenylamine (TPA) pyridinium derivatives with three common pentacyclic triterpenes. Altering the connecting group between the electron donor TPA and the electron acceptor pyridinium resulted in increased production of reactive oxygen species (ROS) by PT-AIEgens and a red-shift in their fluorescence emission spectra. Importantly, the fluorescence emission spectra of BA-3, OA-3, and UA-3 extended into the near-infrared (NIR) range, enabling NIR-AIE imaging of the sites where the derivatives aggregated. The incorporation of the pyridinium structure improved the mitochondrial targeting of PT-AIEgens, enhancing mitochondrial pathway-mediated cell apoptosis and improving the efficiency of chemotherapy (CT) and chemo-photodynamic combined therapy (CPCT) both in vivo and in vitro. Cellular fluorescence imaging demonstrated rapid cellular uptake and mitochondrial accumulation of BA-1 (-2, -3). Cell viability experiments revealed that BA-1 (-2), OA-1 (-2), and UA-1 (-2) exhibited superior CT cytotoxicity compared to their parent drugs, with BA-1 showing the most potent inhibitory effect on HeLa cells (IC = 1.19 μM). Furthermore, HeLa cells treated with BA-1 (1 μM), BA-2 (1.25 μM), and BA-3 (1 μM) exhibited survival rates of 2.99 % ± 0.05 % μM, 5.92 % ± 2.04 % μM, and 2.53 % ± 0.73 % μM, respectively, under white light irradiation. Mechanistic experiments revealed that derivatives induced cell apoptosis via the mitochondrial apoptosis pathway during both CT and CPCT. Remarkably, BA-1 and BA-3 in CPCT inhibited cancer cell proliferation in an in vivo melanoma mouse xenograft model. These results collectively encourage further research of PT-AIEgens as potential anticancer agents.
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http://dx.doi.org/10.1016/j.ejmech.2023.115975 | DOI Listing |
Biomaterials
December 2024
Department of Cardiology, Tianjin Chest Hospital, Tianjin, 300222, China.
In spite of the hypoxia tumor microenvironment, an efficacious treatment with minimal invasiveness is highly desirable. Among common cellular organelles, mitochondria is a common target for inductive cellular apoptosis and tumor proliferation inhibition. Nevertheless, tumor hypoxic circumstances always give rise to poor therapeutic efficiency and instead lead to lesion recurrence and unsatisfactory prognosis.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
College of Basic Medical Sciences, Shanxi Medical University, Taiyuan 030001, PR China; Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, PR China. Electronic address:
Traditional tumor treatment faces great challenge owning to inherent drawbacks. Activatable prodrugs with multi-modality therapeutic capacity are highly desired. In this consideration, a responsiveness-released multi-in-one nanoplatform, PLGA-PEG@HC, toward cervical cancer therapy was innovatively developed.
View Article and Find Full Text PDFInt J Pharm
January 2025
Department of Radiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Integration of different therapeutic performances into one platform is an innovative development for using multiple applications in real-time. In this paper, for the first time we exploited the concurrent capacity of radio and photosensitizing in a theranostic nanoMOFs based on bismuth, zirconium, and porphyrin. The porosity of nanoMOFs provided the capability of doxorubicin loading and chemotherapy besides enhanced photodynamic and radiation therapy (PDT & RT).
View Article and Find Full Text PDFSmall
November 2024
Department of Radiology, The Second Hospital of Jilin University, Changchun, 130041, China.
Combining chemo/photodynamic therapy (CDT/PDT) to generate highly harmful reactive oxygen species and cause mitochondria dysfunction is considered a potential strategy to improve the efficiency of anticancer treatment. However, within tumor, the relatively deficient concentration of HO, hypoxic microenvironment, and overexpressed reduced glutathione (GSH) seriously suppress the efficacy of dynamic therapy. Herein, a multi-functional cascade nanoreactor, bovine serum albumin modified ZnO@CeO-ICG, is reported for remodeling tumor microenvironment (TME) to boost dynamic therapy and realize mitochondria dysfunction via reactive oxygen species (ROS) storm/Zn ions overload.
View Article and Find Full Text PDFNanoscale
November 2024
Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, 411105, PR China.
The combination of chemotherapy and photodynamic therapy holds immense potential for achieving synergistic anti-tumor efficacy. However, challenges such as poor stability and premature drug release prior to reaching tumor sites impede the widespread application of this synergistic therapeutic approach. In this study, a novel ATP-responsive NIR fluorescence nanosystem (CDZ) for imaging-guided chemotherapy and PDT has been developed.
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