Author: Garai, Ildikó ; Szoboszlai, Zoltán ; Csikos, Csaba ; Toàn, Ngô Minh ; Vágner, Adrienn ; Nagy, Gábor ; Tircsó, Gyula ; Kapus, István ; Trencsényi, György ; Váradi, Balázs ; Nagy, Tamás ; Sajtos, Gergő Zoltán ; Szikra, Dezső ; Ország, Gábor

This study aimed to develop a novel radiotracer using trastuzumab and the long-lived [⁵²Mn]Mn isotope for HER2-targeted therapy selection and monitoring. A new Mn(II) chelator, BPPA, synthesized from a rigid bispyclen platform possessing a picolinate pendant arm, formed a stable and inert Mn(II) complex with favorable relaxation properties. BPPA was converted into a bifunctional chelator (BFC), conjugated to trastuzumab, and labeled with [⁵²Mn]Mn isotope. In comparison to DOTA-GA-trastuzumab, the BPPA-trastuzumab conjugate exhibits a labeling efficiency with [⁵²Mn]Mn approximately 2 orders of magnitude higher. In female CB17 SCID mice bearing 4T1 (HER2-) and MDA-MB-HER2+ (HER2+) xenografts, [⁵²Mn]Mn-BPPA-trastuzumab demonstrated superior uptake in HER2+ cells on day 3, with a 3-4 fold difference observed on day 7. Overall, the hexadentate BPPA chelator proves to be exceptional in binding Mn(II). Upon coupling with trastuzumab as a BFC ligand, it becomes an excellent imaging probe for HER2-positive tumors. [⁵²Mn]Mn-BPPA-trastuzumab enables an extended imaging time window and earlier detection of HER2-positive tumors with superior tumor-to-background contrast.

05 Aug 2020·Crystal Growth & Design

Insight from Molecular Packing: Charge Transfer and Emission Modulation through Cocrystal Strategies

Author: Zhang, Shitong ; Jiang, Shimei ; Ding, Zeyang ; Li, Bao ; Han, Wenkun ; Shang, Hongxing

Charge transfer (CT), occurring from donor to acceptor involving π electrons, plays a significant role in regulating the emission of materials.Especially, in multicomponent systems, the CT degree depends on not only the electron rich-deficient abilities of components but also the mol. packing.Herein, three novel cocrystals (BPPa-2I, BPPa-3I, and BPPa-TCNB) based on BPPa, 2I (diiodo-tetrafluorobenzene), 3I (triiodo-trifluorobenzene), and TCNB (1,2,4,5-tetracyanobenzene) are fabricated through halogen bonding (XB) and CT interactions.The three cocrystals exhibit red-shifted emissions from 470 to 505 nm to 530 nm, covering blue via green to yellow, which are attributed to the enhanced CT degrees.On the basis of crystal structural anal., the effective distance between two components in mol. packing is responsible for the different CT degrees; i.e., a fully face-to-face stacking between donor and acceptor can improve the CT degree more effectively.The present study paves an easy way to construct a "packing-CT degree-emission" relationship.Three cocrystals consisting of the same donor (BPPa, cyanostilbene derivative) and three different acceptors (2I (diiodo-tetrafluorobenzene), 3I (triiodo-trifluorobenzene), and TCNB (1,2,4,5-tetracyanobenzene)) were preparedThrough regulating the mol. packing, the cocrystals exhibit enhanced charge transfer degrees and multicolor tunable emissions.

01 Aug 2017·Biomedicine & PharmacotherapyQ2 · MEDICINE

Preparation of a chlorophyll derivative and investigation of its photodynamic activities against cholangiocarcinoma

Q2 · MEDICINE

Article

Author: Wu, Zhong-Ming ; Zhu, Wei ; Wang, Li ; Hu, Tai-Shan ; Wang, Mi ; Yan, Yi-Jia ; Gao, Ying-Hua ; Wu, Hai-Ming ; Chen, Zhi-Long

Photodynamic therapy (PDT) is emerging as a promising method for the treatment of various cancer diseases. However, the clinical application of PDT is limited due to the lack of effective photosensitizers. In this study, a novel chlorophyll derivative, N,N-bis(2-carboxyethyl)pyropheophorbide a (BPPA), had been synthesized and characterized. BPPA had a characteristic long wavelength absorption peak at 669nm and a singlet oxygen quantum yield of 0.54. To investigate the photodynamic ability of BPPA against cholangiocarcinoma (CCA), cellular uptake, subcellular location and bio-distribution, in vitro and in vivo PDT efficacy of BPPA were studied. The results showed that BPPA could rapidly accumulate in QBC-939 cells and localize in the cytoplasm. BPPA- PDT was effective in reducing the cell viability in a drug dose- and light dose-dependent manner in vitro. In CCA xenograft nude mouse model, the concentration of BPPA in the plasma lowered rapidly, and the fluorescence signal peaked at 0.5h and 2h after injection in the skin and tumor, respectively. Significant quantities could be observed in the tumor. BPPA followed by irradiation could significantly inhibit growth of tumors, and histological examination revealed necrotic damage in PDT-treated tumors. These results suggested that BPPA could be a promising drug candidate for photodynamic therapy in cholangiocarcinoma.

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Indication	Highest Phase	Country/Location	Organization	Date
Glaucoma	Phase 2	United States	Merck GmbH	-
Glaucoma	Phase 2	-	Merck Sharp & Dohme Corp.	-

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