Redox- and pH-Responsive Nanoparticles Release Piperlongumine in a Stimuli-Sensitive Manner to Inhibit Pulmonary Metastasis of Colorectal Carcinoma Cells |
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Authors: | Hye Lim Lee Sung Chul Hwang Jae Woon Nah Jungsoo Kim Byungyoul Cha Dae Hwan Kang Young-IL Jeong |
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Affiliation: | 1. Ajou University, School of Medicine, Suwon 61005, Republic of Korea;2. Research Institute of Convergence of Biomedical Sciences, Pusan National University Yangsan Hospital, Gyeongnam 50612, Korea;3. Department of Polymer Science and Engineering, Sunchon National University, Jeonnam 57922, Republic of Korea;4. Gimhae Biomedical Center, Gyeongnam 621-842, Korea;5. Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 49241, Republic of Korea |
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Abstract: | 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. |
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Keywords: | pH responsive redox responsive core cross-linked nanoparticle diselenium reactive oxygen species |
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