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
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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