Fabrication and evaluation of a γ-PGA-based self-assembly transferrin receptor-targeting anticancer drug carrier
Autor: | Xiaoyu Zhu, Li Zhang, Yingjie Liu, Jing Huang, Wenzheng Jiang, Shiming Tan, Shijia Wu, Yazhou Chen |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
targeted drug delivery system Biophysics cisplatin Mice Nude Pharmaceutical Science Antineoplastic Agents Apoptosis Bioengineering Transferrin receptor Pharmacology Fluorescence Flow cytometry Maleimides Biomaterials HeLa Inhibitory Concentration 50 03 medical and health sciences International Journal of Nanomedicine In vivo Receptors Transferrin Drug Discovery Human Umbilical Vein Endothelial Cells medicine Animals Humans Tissue Distribution MTT assay Original Research Cisplatin Drug Carriers biology medicine.diagnostic_test Chemistry Body Weight Organic Chemistry General Medicine biology.organism_classification Acute toxicity side effects 030104 developmental biology Polyglutamic Acid Organ Specificity Toxicity Female tumor suppression Peptides HeLa Cells medicine.drug |
Zdroj: | International Journal of Nanomedicine |
ISSN: | 1178-2013 |
Popis: | Li Zhang, Xiaoyu Zhu, Shijia Wu, Yazhou Chen, Shiming Tan, Yingjie Liu, Wenzheng Jiang, Jing Huang School of Life Sciences, East China Normal University, Shanghai 200241, China Background: cis-Dichlorodiamineplatinum (CDDP) was one of the most common used drugs in clinic for cancer treatment. However, CDDP caused a variety of side effects. The abundant carboxyl groups on the surface of poly glutamic acid (PGA) could be modified with various kinds of targeted ligands. PGA delivery system loaded CDDP for cancer therapies possesses potential to overcome the side effects.Materials and methods: In this study, we constructed a safe and efficient anticancer drug delivery system PGA–Asp–maleimide–cisplatin–peptide complex (PAMCP), which was loaded with CDDP and conjugated with the transferrin receptor (TFR)-targeting peptide through a maleimide functional linker. The size of PAMCP was identified by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Fluorescence microscopy and flow cytometry methods were used to detect the cell targeting ability in vitro. The MTT assay was used to detect targeted toxicity in vitro. The in vivo acute toxicity was tested in Kun Ming (KM) mice. The tumor suppression activity and drug distribution was analyzed in nude mice bearing with HeLa tumor cells.Results: The nano-size was 110±28 nm detected with TEM and 89±18 nm detected with DLS, respectively. Fluorescence microscopy and flow cytometry methods indicated that PAMCP possessed excellent cell targeting ability in vitro. The MTT assay suggested that PAMCP was excellent for targeted toxicity. The acute in vivo toxicity study revealed that the body mass index and serum index in the PAMCP-treated group were superior to those in the CDDP-treated group (P |
Databáze: | OpenAIRE |
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