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International Journal of Peptide Research and Therapeutics · 2020 ·Vol. 26 ·期 4 ·2285-2296 · IF 1.5

Anticancer Activity and Mechanism of Action of kla-TAT Peptide

Chen Xiaolong,Hu Cuihua,Zhang Yanan,Hao Wenjing,He Xu,Li Qing,Huang Yuxi,Huang Yibing,Chen Yuxin

Conjugation of cell-penetrating peptides to anticancer peptides is an effective strategy to enhance tumor treatment. The hybrid peptide, kla-TAT, by attaching the TAT peptide to the C-terminus of the pro-apoptotic peptide kla exhibited strong anticancer activity when co-administration with other peptide, but the systematic mechanism was not clear. In this study, the mechanisms of action of kla-TAT including the uptake pathway, distribution in cytoplasm, apoptosis-inducing ability and micro-morphology were investigated. The results indicated that the hybrid peptide internalized into A549 cells through two transmembrane mechanisms: endocytosis mediated by the clathrin-mediated endocytosis route and the rapid membrane disruption mechanism. Peptides that were endocytosed could interact with the mitochondrial membrane, while peptides internalized by disrupting the cell membrane caused disruption of the mitochondrial membrane. Thus, the hybrid kla-TAT peptide transfers through the cell membrane, inducing apoptosis by destroying the mitochondrial membrane and causethe expression of cyclin-D1 down-regulation. Meanwhile, the changes of the micro-morphology of the cancer cells was detected using atomic force microscope (AFM) and scanning electron microscope (SEM), which provided the visualized evidence for the mechanism of the peptides.

研究领域: 癌症生物学 · 药学 · 细胞生物学 · 分子生物学
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JOURNAL OF SOLID STATE CHEMISTRY · 2025 · IF 3.5

Sm3+ -activated KLa(WO4)2 phosphors with Gd3+ Co-doping: Orange-Red emission and thermal stability toward potential plant lighting applications

Lanwei Qiu,Haochang Ye,Guangting Xiong,Wei Zhang,Yirong Huang,Qiuzhi Liang,Canhui Pan,Jinquan Chen,Zuyong Feng

Orange-red KLa(WO 4 ) 2 phosphors co-doped with Sm 3+ -Gd 3+ were synthesized via high-temperature solid-state reaction. Phase purity and crystal structure were confirmed by XRD, while SEM revealed non-uniform particle distribution. XPS verified elemental composition and suggested the chemical states of dopants. Under 403 nm excitation, KLa(WO 4 ) 2 : Sm 3+ exhibited intense orange–red emissions, dominated by the 4 G 5/2 - 6 Hᵢ (i = 5/2, 7/2, 9/2, 11/2) transition from 500 to 750 nm. Substitution by Gd 3+ lowers the local symmetry, as evidenced by the increased asymmetry ratio, resulting in a 1.88-fold increase in emission intensity. Notably, the optimized phosphor, KLa 0.8 Gd 0.15 (WO 4 ) 2 :0.05Sm 3+ , exhibits a high color purity (CP) of 99 % and excellent thermal stability retaining 85 % of its room-temperature emission intensity at 423K. When combined with a 405 nm InGaN chip, the fabricated LED displayed strong spectral overlap with chlorophyll and phytochrome absorption peaks, confirming its potential for plant-growth illumination.

CAS / MDL: 12060-58-1 1312-81-8
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APOPTOSIS · 2018 ·Vol. 23 ·期 2 ·132-142 · IF 3.967

Synergistic effect of the pro-apoptosis peptide kla-TAT and the cationic anticancer peptide HPRP-A1

Hu Cuihua,Chen Xiaolong,Huang Yibing,Chen Yuxin

In this study, a peptide–peptide co-administration therapy between hybrid peptide kla-TAT and cationic anticancer peptide HPRP-A1 was designed to increase the anticancer activity of the combination peptides through synergistic effect. kla is a pro-apoptotic peptide which could induce rapid cancer cell apoptosis by disruption the mitochondrial membrane when internalized the cells. To enhance more kla peptides pass through cell membrane, a double improvement strategy was designed by chemically conjugation with cell penetration peptide TAT as well as co-administration with cationic membrane active peptide HPRP-A1, and the double anticancer mechanism of the kla-TAT peptide and HPRP-A1 including membrane disruption and apoptosis induction was verified through in vitro experiments. The CompuSyn synergism/antagonism analysis showed that kla-TAT acted synergistically with HPRP-A1 against a non-small cell lung cancer (NSCLC) A549 cell line. The anticancer activities of the two peptides were dramatically increased by co-administration, under the mechanism of cell membrane disruption, caspase-dependent apoptosis induction, as well as cyclin-D1 down-regulation based G1 phase arrest. We believe that the synergic therapeutic strategy would be a meaningful method for the anticancer peptides used in cancer treatment.

CAS / MDL: 62669-70-9
研究领域: 肿瘤学 · 药学 · 细胞生物学
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JOURNAL OF ALLOYS AND COMPOUNDS · 2021 · IF 5.316

Tunable KLa(MoO4)2:Eu3+@CDs composite materials for white LED and multi-mode information encryption technology

Ziqian Lv,Hanyu Xu,Zhiying Wang,Mochen Jia,Yanling Wei,Zuoling Fu

The composite of biocompatible carbon dots (CDs) and lanthanide-based luminescent materials have high research value as a promising multifunctional material, which are ideally suited to information encryption and white LED. However, the aggregation-induced quenching of CDs in the solid state still troubles the synthesis of CDs with other solid luminescent materials. Herein, a facile strategy to fabricate polychromatic nanoplatform KLa(MoO 4 ) 2 : Eu 3+ @CDs by encapsulating CDs on the surface of KLM: Eu 3+ with silicon shell is reported, in which the aggregation-induced quenching of CDs is avoided. Due to the overlapping of Eu-O charge transfer band with CDs excitation band, the red luminescence of Eu 3+ ions and the blue fluorescence of can be emitted simultaneously under 395 nm excitation. By changing the proportion of KLa(MoO 4 ) 2 : Eu 3+ in KLa(MoO 4 ) 2 : Eu 3+ @CDs, the mixture can emit "warm", "neutral", and "cold" white light, which can realize people's demand for indoor lighting requirements. Furthermore, a multi-mode information encryption by selectively triggering the luminescence of CDs or Eu 3+ ions is also designed. All the results suggest that KLa(MoO 4 ) 2 : Eu 3+ @CDs have excellent luminescence properties that can be further investigated and applied in the field of white LEDs and information encryption.

研究领域: 材料科学 · 光学 · 信息加密技术
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Pharmaceuticals · 2022 ·Vol. 15 ·期 7 ·881 · IF 5.215

Co-Delivery of 5-Fluorouracil and Paclitaxel in Mitochondria-Targeted KLA-Modified Liposomes to Improve Triple-Negative Breast Cancer Treatment

Tianyu Chen,Hui Chen,Yichun Jiang,Qi Yan,Shuling Zheng,Min Wu

In this research, KLA-modified liposomes co-loaded with 5-fluorouracil and paclitaxel (KLA-5-FU/PTX Lps) were developed, and their antitumor activity against triple-negative breast cancer (TNBC) was evaluated. KLA-5-FU/PTX Lps were prepared using the thin-film dispersion method, and their in vitro anticancer efficacy was assessed in human breast cancer cells (MDA-MB-231). An MDA-MB-231 tumor-bearing mouse model was also established to evaluate their antitumor efficacy in vivo. KLA-5-FU/PTX Lps showed enhanced cytotoxicity against MDA-MB-231 cells, improved drug delivery to mitochondria, and induced mitochondria-mediated apoptosis. The modified liposomes also showed favorable antitumor activity in vivo due to their strong ability to target tumors and mitochondria. The liposomes showed no obvious systemic toxicity. Our results suggest that KLA-5-FU/PTX Lps are a promising system with which to target the delivery of antitumor drugs to mitochondria as a treatment for TNBC.Keywords:5-fluorouracil;paclitaxel;liposomes;mitochondrial targeting;TNBC

CAS / MDL: 51-21-8 33069-62-4
研究领域: 药理学 · 肿瘤学 · 纳米技术
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BIOMEDICAL CHROMATOGRAPHY · 2017 ·Vol. 32 ·期 2 ·e4094 · IF 1.613

Anti-inflammatory activities and glycerophospholipids metabolism in KLA-stimulated RAW 264.7 macrophage cells by diarylheptanoids from the rhizomes of Alpinia officinarum

Guogai Zhang,Lifang Zhao,Jiancheng Zhu,Yifan Feng,Xia Wu

Alpinia officinarum is used for its anti-inflammatory activity historically in China. Diarylheptanoids isolated from A. officinarum play important biological roles in the prevention and treatment of inflammatory disorders. Seven diarylheptanoids (1–7) were isolated from A. officinarum . The cell viabilities and anti-inflammatory activities of diarylheptanoids were evaluated by MTT assay and tumor necrosis factor- α production in Kdo2-lipid A-stimulated RAW 264.7 cells in vitro . The relationships between their anti-inflammatories and structure-activities are discussed. The results indicated that compounds 1 and 3–7 had significant anti-inflammatory activities. The relationships between inflammation and phospholipids metabolism were elucidated by multivariate data analysis. Twenty-two potential biomarkers were identified in inflammatory group vs. blank group, and 11 potential biomarkers were identified for inflammatory group vs. drug-treatment groups. Ten common phospholipids were characterized. On the basis of a previous study in our laboratory, we found that phosphatidylethanolamine (18:0/18:1) might be the important glycerophospholipid biomarker in inflammation. In this study, we firstly combined anti-inflammatory activities and glycerophospholipids changes of traditional Chinese medicine. This work suggests that the anti-inflammatory activities of diarylheptanoids might be significantly related to glycerophospholipids and could provide a useful database for investigating the anti-inflammatory effects of traditional Chinese medicine.

CAS / MDL: 64-19-7
研究领域: 药理学 · 生物化学 · 中药学 · 细胞生物学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2016 · IF 3.902

Nanosystem composed with MSNs, gadolinium, liposome and cytotoxic peptides for tumor theranostics

Yaqing Jin,Nengpan Zhang,Chunlin Li,Kefeng Pu,Chen Ding,Yimin Zhu

A dual-functional delivery system, based on mesoporous silica nanoparticles (MSNs) with the integration of Magnetic Resonance (MR) imaging and therapeutic peptide delivery, is reported in this paper. A lipid bilayer is attached onto the surface of the nanoparticles, following the doping of Gadolinium (Gd), a paramagnetic lanthanide ion. The liposome-coated GdMSNs exhibit improved colloidal stability, better biocompatibility and more efficient cellular uptake. The Gd renders the nano carrier a potential T1 contrast agent, confirmed by the MR imaging. A pro-apoptotic peptide, KLA (HGGKLAKLAKKLAKLAK), is encapsulated into the GdMSNs-LP and enters into the cells successfully to induce mitochondrial swelling and apoptosis, while it is nontoxic outside the cells. The synthesis procedure is convenient and free of toxic organic reagents. The nanosystem we construct may contribute to a promising theranostic platform for therapeutic peptide delivery in cancer treatment.

研究领域: 纳米技术 · 生物医学工程 · 癌症研究 · 材料科学 · 药学
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