한빛사 논문
충남대학교
Saji Uthamana, Shameer Pillarisettib, Ansuja Pulickal Mathewb, Yugyeong Kima, Woo Kyun Baec, Kang Moo Huha,*, In-Kyu Parkb,*
a Department of Polymer Science and Engineering, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea
b Department of Biomedical Sciences, Chonnam National University Medical School, 160 Baekseo-ro, Gwangju, 58128, Republic of Korea
c Department of Hematology-Oncology, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Republic of Korea
*Corresponding author : Kang Moo Huh, In-Kyu Park
Abstract
Although chemo-photodynamic therapy demonstrates promising synergetic therapeutic effect in malignant cancers, the currently available nanocarriers offer the limited capabilities for selective toxicity, drug release and tumor penetration. Herein, we developed photoactivatable nanomicelles, which are constructed by self-assembling of poly (ethylene glycol) (PEG)-stearamine (C18) conjugate (PTS) with a ROS-sensitive thioketal linker (TL) and co-loaded with doxorubicin (DOX) and photosensitizer pheophorbide A (PhA), for enhanced locoregional chemo-photodynamic therapy. Upon accumulation in tumor region, the resulting PTS nanomicelles loaded with Dox and PhA (PTS-DP) demonstrated reactive oxygen species (ROS) cascade responsive release of the DOX and PhA loaded inside. Initial intracellular release of DOX and PhA from the PTS-DP was triggered by the intrinsic presence of endogenous ROS within cancer cells. Furthermore, upon laser irradiation on the tumor region, enhanced singlet oxygen (1O2) was generated by PhA released initially in cancer cells, which in turns accelerated the cytoplasmic release of DOX through rapid dissociation of nanomicelles. The gradual elevation of local ROS level generated by light-activated PhA subsequent ROS-triggered release of DOX synergistically inhibited tumor growth and enhances the anti-tumor immunity. Findings of our study suggested that ROS-sensitive PTS nanomicelles could be a promising and innovative nanocarrier for locoregional chemo-photodynamic therapy.
Keywords
Photoactivable; ROS sensitive linker; Nanomicelles; Locoregional chemo-photodynamic therapy; Antitumor immunity
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