In a multi-bubble system, the bubble behavior is modulated by the primary acoustic field and the secondary acoustic field. To explore the translational motion of bubbles in cavitation liquids containing high-concentra...In a multi-bubble system, the bubble behavior is modulated by the primary acoustic field and the secondary acoustic field. To explore the translational motion of bubbles in cavitation liquids containing high-concentration cavitation nuclei,evolutions of bubbles are recorded by a high-speed camera, and translational trajectories of several representative bubbles are traced. It is found that translational motion of bubbles is always accompanied by the fragmentation and coalescence of bubbles, and for bubbles smaller than 10 μm, the possibility of bubble coalescence is enhanced when the spacing of bubbles is less than 30 μm. The measured signals and their spectra show the presence of strong negative pressure, broadband noise,and various harmonics, which implies that multiple interactions of bubbles appear in the region of high-intensity cavitation.Due to the strong coupling effect, the interaction between bubbles is random. A simplified triple-bubble model is developed to explore the interaction patterns of bubbles affected by the surrounding bubbles. Patterns of bubble interaction, such as attraction, repulsion, stable spacing, and rebound of bubbles, can be predicted by the theoretical analysis, and the obtained results are in good agreement with experimental observations. Mass exchange between the liquid and bubbles as well as absorption in the cavitation nuclei also plays an important role in multi-bubble cavitation, which may account for the weakening of the radial oscillations of bubbles.展开更多
The combination of endocrine therapy and chemotherapy is an attractive approach for treating breast cancers. Aromatase inhibitors (AIs) are the first-line drugs for postmenopausal ER-positive breast cancer and adjuvan...The combination of endocrine therapy and chemotherapy is an attractive approach for treating breast cancers. Aromatase inhibitors (AIs) are the first-line drugs for postmenopausal ER-positive breast cancer and adjuvant therapy drugs for early stages of breast cancer. In this paper,we employed the FDA-approved aromatase inhibitor aminoglutethimide (AG) to design and prepare a new class of multi-targeting Pt(IV) prodrugs (aminoplatins 1–3) by utilizing the targeting,estrogen-manipulating,and chemo-sensitizing effects of the aromatase inhibitor. Aminoplatin 3,as a representative,exhibited an enhanced anticancer activity up to 190-fold greater than the parent Pt(Ⅱ) drug cisplatin,and 3 had less toxicity to normal cells,displaying higher anticancer efficacy and a superior therapeutic index compared to those of cisplatin. Moreover,aminoplatin 3 could enhance intracellular accumulation,induce remarkable DNA damage,inhibit migration and metastasis,and result in S phase cell cycle arrest and apoptosis in ER-positive MCF-7 cells. Besides,molecular docking results showed that 3 simultaneously occupies the heme iron-binding domain and the ASD-binding site of aromatase by a highly efficient dual-binding pattern to aromatase,which further displayed a striking anti-estrogenic effect by significant downregulation of CPY19A1 and ERα in ER-positive MCF-7 cells. Most strikingly,our in vivo anticancer evaluation data also provided evidence that 3 effectively inhibited tumor growth and attenuated kidney toxicity compared to cisplatin in MCF-7 xenografted BALB/c nude mice. Our results suggest that the anticancer activity of aminoplatins is mechanistically distinct from that of the conventional platinum drugs,and modifying platinum drugs with aromatase inhibitors may represent an improved modality for the treatment of advanced postmenopausal breast cancer.展开更多
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11974232 and 12374441)the Fund from the Yulin Science and Technology Bureau,China(Grant No.CXY-2022-178).
文摘In a multi-bubble system, the bubble behavior is modulated by the primary acoustic field and the secondary acoustic field. To explore the translational motion of bubbles in cavitation liquids containing high-concentration cavitation nuclei,evolutions of bubbles are recorded by a high-speed camera, and translational trajectories of several representative bubbles are traced. It is found that translational motion of bubbles is always accompanied by the fragmentation and coalescence of bubbles, and for bubbles smaller than 10 μm, the possibility of bubble coalescence is enhanced when the spacing of bubbles is less than 30 μm. The measured signals and their spectra show the presence of strong negative pressure, broadband noise,and various harmonics, which implies that multiple interactions of bubbles appear in the region of high-intensity cavitation.Due to the strong coupling effect, the interaction between bubbles is random. A simplified triple-bubble model is developed to explore the interaction patterns of bubbles affected by the surrounding bubbles. Patterns of bubble interaction, such as attraction, repulsion, stable spacing, and rebound of bubbles, can be predicted by the theoretical analysis, and the obtained results are in good agreement with experimental observations. Mass exchange between the liquid and bubbles as well as absorption in the cavitation nuclei also plays an important role in multi-bubble cavitation, which may account for the weakening of the radial oscillations of bubbles.
基金supported by the National Natural Science Foundation of China(21977080,21371135,and 21772146)Tianjin Municipal Natural Science Foundation(17JCZDJC33100).
文摘The combination of endocrine therapy and chemotherapy is an attractive approach for treating breast cancers. Aromatase inhibitors (AIs) are the first-line drugs for postmenopausal ER-positive breast cancer and adjuvant therapy drugs for early stages of breast cancer. In this paper,we employed the FDA-approved aromatase inhibitor aminoglutethimide (AG) to design and prepare a new class of multi-targeting Pt(IV) prodrugs (aminoplatins 1–3) by utilizing the targeting,estrogen-manipulating,and chemo-sensitizing effects of the aromatase inhibitor. Aminoplatin 3,as a representative,exhibited an enhanced anticancer activity up to 190-fold greater than the parent Pt(Ⅱ) drug cisplatin,and 3 had less toxicity to normal cells,displaying higher anticancer efficacy and a superior therapeutic index compared to those of cisplatin. Moreover,aminoplatin 3 could enhance intracellular accumulation,induce remarkable DNA damage,inhibit migration and metastasis,and result in S phase cell cycle arrest and apoptosis in ER-positive MCF-7 cells. Besides,molecular docking results showed that 3 simultaneously occupies the heme iron-binding domain and the ASD-binding site of aromatase by a highly efficient dual-binding pattern to aromatase,which further displayed a striking anti-estrogenic effect by significant downregulation of CPY19A1 and ERα in ER-positive MCF-7 cells. Most strikingly,our in vivo anticancer evaluation data also provided evidence that 3 effectively inhibited tumor growth and attenuated kidney toxicity compared to cisplatin in MCF-7 xenografted BALB/c nude mice. Our results suggest that the anticancer activity of aminoplatins is mechanistically distinct from that of the conventional platinum drugs,and modifying platinum drugs with aromatase inhibitors may represent an improved modality for the treatment of advanced postmenopausal breast cancer.
