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5. Fructose and biotin co-modified liposomes for dual-targeting breast cancer.

Author

Li, Ru, Peng, Yao, Pu, Yanchi, Zhao, Yi, Nie, Ruifang, Guo, Li, and Wu, Yong

Subjects
LIPOSOMES, BREAST cancer, FRUCTOSE, BIOTIN, DRUG delivery systems, ENDOCYTOSIS
Abstract

Chemotherapy, as the main treatment for breast cancer, inevitably damages normal tissues due to the lack of targeting. Various nano targeting drug delivery systems (TDDS) have the potential to be developed as anticancer therapeutics. Although mono-ligand-directed liposomes have been used with some success, dual-ligand-directed liposomes exhibit promising advantages. In current work, we synthesized a Y-shaped ligand covalently linking fructose and biotin (Fru-Bio-Chol) to prepare a dual-targeting liposome Fru-Bio-Lip for breast cancer. The targeting ability was evaluated by comparing the Fru-Bio-Lip with the non-modified liposome (Lip), fructose or biotin mono modified liposomes (Fru-Lip and Bio-Lip), and another dual-targeting liposome (Fru + Bio-Lip) physically mixing fructose and biotin mono modified ligands (Fru-Chol and Bio-Chol). The cellular uptake of Fru-Bio-Lip is 3.27-, 1.81-, 2.19-, 1.15-times that of Lip, Fru-Lip, Bio-Lip and Fru + Bio-Lip on 4T1 cells, and 3.11-, 1.80-, 1.89-, 1.15-times on MCF-7 cells. Additionally, the uptake mechanism indicates the uptake of Fru-Bio-Lip is energy-dependently achieved through multiple endocytosis pathway with a dual recognition of fructose and biotin by GLUT5 and SMVT. The cytotoxicity and apoptosis assay show PTX-Fru-Bio-Lip among liposomes have the strongest proliferation inhibitory effect on breast cancer cells, and the apoptosis rate is 1.7-times that of PTX-Lip. In vivo images indicate Fru-Bio-Lip have the strongest tumour enrichment ability, which is 2.76-, 1.60-, 1.96-, 1.40-times that of Lip, Fru-Lip, Bio-Lip and Fru + Bio-Lip, respectively. Overall, the fructose and biotin covalently modified liposomes improved breast cancer targeting ability, demonstrating great potential as a drug delivery system for breast cancer. [ABSTRACT FROM AUTHOR]

Published
2022
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6. Design, preparation and evaluation of different branched biotin modified liposomes for targeting breast cancer

Author

Li Hai, Li Guo, Yong Wu, Qiming Yue, Pu Yanchi, Ru Li, Baolan Tang, Yi Zhao, and Yao Peng

Subjects
media_common.quotation_subject, Biotin, Antineoplastic Agents, Apoptosis, Breast Neoplasms, Ligands, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Mice, Structure-Activity Relationship, Breast cancer, stomatognathic system, Cell Line, Tumor, Drug Discovery, medicine, Animals, Humans, Cytotoxicity, Receptor, Internalization, 030304 developmental biology, media_common, Cell Proliferation, Pharmacology, 0303 health sciences, Liposome, Dose-Response Relationship, Drug, Molecular Structure, 010405 organic chemistry, Organic Chemistry, General Medicine, medicine.disease, 0104 chemical sciences, Molecular Docking Simulation, stomatognathic diseases, Cholesterol, chemistry, Drug Design, Drug delivery, Cancer cell, Liposomes, Cancer research, MCF-7 Cells, Female, Drug Screening Assays, Antitumor
Abstract

A series of liposome ligands (Bio-Chol, Bio-Bio-Chol, tri-Bio-Chol and tetra-Bio-Chol) modified by different branched biotins that can recognize the SMVT receptors over-expressed in breast cancer cells were synthesized. And four liposomes (Bio-Lip, Bio-Bio-Lip, tri-Bio-Lip and tetra-Bio-Lip) modified by above mentioned ligands as well as the unmodified liposome (Lip) were prepared to study the targeting ability for breast cancer. The cytotoxicity study and apoptosis assay of paclitaxel-loaded liposomes showed that tri-Bio-Lip had the strongest anti-proliferative effect on breast cancer cells. The cellular uptake studies on mice breast cancer cells (4T1) and human breast cancer cells (MCF-7) indicated tri-Bio-Lip possessed the strongest internalization ability, which was 5.21 times of Lip, 2.60 times of Bio-Lip, 1.67 times of Bio-Bio-Lip and 1.17 times of tetra-Bio-Lip, respectively. Moreover, the 4T1 tumor-bearing BALB/c mice were used to evaluate the in vivo targeting ability. The data showed the enrichment of liposomes at tumor sites were tri-Bio-Lip > tetra-Bio-Lip > Bio-Bio-Lip > Bio-Lip > Lip, which were consistent with the results of in vitro targeting studies. In conclusion, increasing the density of targeting molecules on the surface of liposomes can effectively enhance the breast cancer targeting ability, and the branching structure and spatial distance of biotin residues may also have an important influence on the affinity to SMVT receptors. Therefore, tri-Bio-Lip could be a promising drug delivery system for targeting breast cancer.

Published
2019

7. Biotin and glucose dual-targeting, ligand-modified liposomes promote breast tumor-specific drug delivery

Author

Li Guo, Yong Wu, Yao Peng, Qiuyi Fu, Mengyi Huang, Yongxiang Zheng, and Pu Yanchi

Subjects
Paclitaxel, medicine.medical_treatment, Clinical Biochemistry, Pharmaceutical Science, Biotin, Breast Neoplasms, Ligands, 01 natural sciences, Biochemistry, Mice, Structure-Activity Relationship, Breast cancer, Therapeutic index, Drug Delivery Systems, In vivo, Cell Line, Tumor, Drug Discovery, medicine, Animals, Humans, Cytotoxicity, Molecular Biology, Liposome, Chemotherapy, Drug Carriers, Dose-Response Relationship, Drug, Molecular Structure, 010405 organic chemistry, Chemistry, Organic Chemistry, Mammary Neoplasms, Experimental, medicine.disease, Antineoplastic Agents, Phytogenic, In vitro, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Glucose, Drug delivery, Liposomes, Cancer research, Molecular Medicine, Female
Abstract

Breast cancer is the second leading cause of cancer-related deaths in women. Ligand-modified liposomes are used for breast tumor-specific drug delivery to improve the efficacy and reduce the side effects of chemotherapy; however, only a few liposomes with high targeting efficiency have been developed because the mono-targeting, ligand-modified liposomes are generally unable to deliver an adequate therapeutic dose. In this study, we designed biotin-glucose branched ligand-modified, dual-targeting liposomes (Bio-Glu-Lip) and evaluated their potential as a targeted chemotherapy delivery system in vitro and in vivo. When compared with the non-targeting liposome (Lip), Bio-Lip, and Glu-Lip, Bio-Glu-Lip had the highest cell uptake in 4T1 cells (3.00-fold, 1.60-fold, and 1.95-fold higher, respectively) and in MCF-7 cells (2.63-fold, 1.63-fold, and 1.85-fold higher, respectively). The subsequent cytotoxicity and in vivo assays further supported the dual-targeting liposome is a promising drug delivery carrier for the treatment of breast cancer.

Published
2019

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