Dual pH- and GSH-Responsive Degradable PEGylated Graphene Quantum Dot-Based Nanoparticles for Enhanced HER2-Positive Breast Cancer Therapy
Na Re Ko,
Se Young Van,
Sung Hwa Hong,
Seog-Young Kim,
Miran Kim,
Jae Seo Lee,
Sang Ju Lee,
Yong-kyu Lee,
Il Keun Kwon,
Seung Jun Oh
Affiliations
Na Re Ko
Biomedical Research Center, Asan Institute for Life Sciences, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
Se Young Van
Biomedical Research Center, Asan Institute for Life Sciences, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
Sung Hwa Hong
Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada
Seog-Young Kim
Department of Convergence Medicine, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
Miran Kim
Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
Jae Seo Lee
Department of Dental Materials, School of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
Sang Ju Lee
Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
Yong-kyu Lee
Department of Chemical & Biological Engineering, Korea National University of Transportation, 50 Daehak-ro, Chungcheongbuk-do, Cheongju 27469, Korea
Il Keun Kwon
Department of Dental Materials, School of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
Seung Jun Oh
Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
Dual stimuli-responsive degradable carbon-based nanoparticles (DS-CNPs) conjugated with Herceptin (HER) and polyethylene glycol (PEG) have been designed for the treatment of HER2-positive breast cancer. Each component has been linked through disulfide linkages that are sensitive to glutathione in a cancer microenvironment. β-cyclodextrin (β-CD) on the surface of DS-CNPs formed an inclusion complex (DL-CNPs) with doxorubicin (DOX) at a high loading capacity of 5.3 ± 0.4%. In response to a high level of glutathione (GSH) and low pH in a tumor environment, DL-CNPs were rapidly degraded and released DOX in a controlled manner via disruption of host−guest inclusion. These novel DL-CNPs exhibited high cellular uptake with low toxicity, which induced the efficient inhibition of antitumor activity both in vitro and in vivo. Cell viability, confocal laser scanning microscopy, and animal studies indicate that DL-CNPs are a great platform with a synergistically enhanced antitumor effect from the dual delivery of HER and DOX in DL-CNPs.
