Redox- and pH-Responsive Nanoparticles Release Piperlongumine in a Stimuli-Sensitive Manner to Inhibit Pulmonary Metastasis of Colorectal Carcinoma Cells
| Autor: | Jung-Soo Kim, Hye Lim Lee, Young-Il Jeong, Jae Woon Nah, Sung Chul Hwang, Byungyoul Cha, Dae Hwan Kang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Lung Neoplasms Pharmaceutical Science Nanoparticle Antineoplastic Agents Polyethylene Glycols Chitosan Diselenide 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems Cell Line Tumor Humans Histidine Piperlongumine chemistry.chemical_classification Drug Carriers Reactive oxygen species Dioxolanes Hydrogen-Ion Concentration 030104 developmental biology chemistry A549 Cells Cancer cell Biophysics Nanoparticles Colorectal Neoplasms Oxidation-Reduction Ethylene glycol |
| Zdroj: | Journal of Pharmaceutical Sciences. 107:2702-2712 |
| ISSN: | 0022-3549 |
| DOI: | 10.1016/j.xphs.2018.06.011 |
| Popis: | Redox-responsive nanoparticles having a diselenide linkage were synthesized to target pulmonary metastasis of cancer cells. Methoxy poly(ethylene glycol)-grafted chitosan (ChitoPEG) was crosslinked using selenocystine-acetyl histidine (Ac-histidine) conjugates (ChitoPEGse) for stimuli-responsive delivery of piperlongumine (PL). ChitoPEGse nanoparticles swelled in an acidic environment and became partially disintegrated in the presence of H2O2, resulting in an increase of particle size and in a size distribution having multimodal pattern. PL release increased under acidic conditions and in the presence of H2O2. Uptake of ChitoPEGse nanoparticles by CT26 cells significantly increased in acidic and redox state. PL-incorporated ChitoPEGse nanoparticles (PL NPs) showed similar anticancer activity in vitro against A549 and CT26 cells compared to PL itself. PL NP showed superior anticancer and antimetastatic activity in an in vivo CT26 cell pulmonary metastasis mouse model. Furthermore, an immunofluorescence imaging study demonstrated that PL NP conjugates were specifically delivered to the tumor mass in the lung. Conclusively, ChitoPEGse nanoparticles were able to be delivered to cancer cells with an acidic- or redox state-sensitive manner and then efficiently targeted pulmonary metastasis of cancer cells since ChitoPEGse nanoparticles have dual pH- and redox-responsiveness. |
| Databáze: | OpenAIRE |
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