1. Construction of redox-responsive tumor targeted cisplatin nano-delivery system for effective cancer chemotherapy.
- Author
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Jia YY, Zhang JJ, Zhang YX, Wang W, Li C, Zhou SY, and Zhang BL
- Subjects
- A549 Cells, Animals, Antineoplastic Agents chemistry, Antineoplastic Agents metabolism, Cell Survival drug effects, Cell Survival physiology, Cisplatin chemistry, Cisplatin metabolism, Dose-Response Relationship, Drug, Humans, Mice, Mice, Inbred BALB C, Mice, Nude, Nanoparticles chemistry, Nanoparticles metabolism, Neoplasms metabolism, Neoplasms pathology, Oxidation-Reduction drug effects, Treatment Outcome, Xenograft Model Antitumor Assays methods, Antineoplastic Agents administration & dosage, Cisplatin administration & dosage, Drug Delivery Systems methods, Nanoparticles administration & dosage, Neoplasms drug therapy
- Abstract
Cisplatin is one of the most widely used platinum-based anticancer chemotherapeutic drugs. However, its low solubility, serious side effects and the development of cisplatin resistance limit its further use in the clinic. Controlling the delivery and release of cisplatin at the targeted site efficiently is a meaningful way to overcome these undesirable side effects of cisplatin. Herein, a tumor targeted and stimuli responsive nano-delivery system for cisplatin was constructed using branched polyethyleneimine (BPEI) as the backbone, disulfide bond as the redox-responsive covalent linker and hyaluronic acid (HA) as targeting recognition unit which can bind selectively to the receptor of CD44, which is highly expressed on the A549 tumor cells. The cisplatin-polyethyleneimine conjugate BPEI-SS-Pt was prepared and the drug loading of cisplatin was up to 32.66 ± 0.06%. After optimized the coating weight ratio of HA and BPEI-SS-Pt, the nanoparticle delivery system HA-(BPEI-SS-Pt)-1/4 outperformed with smaller particle size of 159.0 ± 21.0 nm, narrow polydispersity index (PDI) of 0.069 ± 0.022 and higher cisplatin loading of 29.23 ± 0.18%, showing specific tumor-targeting ability and redox-responsive drug release manner. Moreover, for the treatment of cancer in vivo, it achieved more effective antitumor performance along with minor side effects and systemic toxicity compared with cisplatin which is of great significance for the chemotherapeutic drug in the clinic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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