Intracellular delivery and activation of the genetically encoded photosensitizer Killer Red by quantum dots encapsulated in polymeric micelles.
We have prepared polymeric micelle-encapsulating quantum dots (QDots) for delivering the optically activatable protein Killer Red (KR) as a plasmid to cancer cells. QDots absorb light at a lower wavelength and emit light at a higher wavelength in the cell cytoplasm, activating the expressed KR. Once activated, KR triggers the generation of reactive oxygen species (ROS). We prepared cadmium selenide (CdSe)/zinc sulphide (ZnS) QDots and evaluated their optical properties. Subsequently, we performed morphology studies, elemental analysis, thermogravimetric analysis (TGA), and measurements of particle size and surface charge of prepared QDots encapsulated in PHEA-g-PEG-bPEI (PPP-QDot). Cellular uptake of PPP-QDot and PPP-QDot/KR nanoparticles was confirmed using confocal microscopy, and the cellular toxicity and transfection efficiency associated with uptake of PPP-QDot/KR nanoparticles were analyzed. KR expression in normal cells and cancer cells was confirmed using confocal microscopy and Western blotting. Cellular morphologies before and after intracellular activation of KR were observed using phase contrast, fluorescence, and confocal microscopy. Cell fate after exposure to blue light-emitting diode lighting was determined using apoptosis staining and a cell proliferation assay, confirming a suppression in proliferation and a reduction in metabolic activity. We determined that ROS generation contributed to cellular damage after treatment with PPP-QDot/KR nanoparticles and blue light exposure.
Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju 501-746, South Korea.
Muthunarayanan
M
Muthiah
Department of Nuclear medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
Seung-Hwan
SH
Park
Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungbuk 380-702, South Korea.
Md
M
Nurunnabi
Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungbuk 380-702, South Korea.
Jooyoung
J
Lee
Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungbuk 380-702, South Korea.
Yong-Kyu
YK
Lee
School of Integrative Engineering, Chung-Ang University, Dongjak-gu, Seoul 156-756, South Korea.
Hansoo
H
Park
Medical Photonics Research Center, Korea Photonics Research Center, Buk-go, Gwangju 507-779, South Korea.
Byeong-Il
BI
Lee
Department of Nuclear medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
Jung-Joon
JJ
Min
Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju 501-746, South Korea. Electronic address: pik96@chonnam.ac.kr.
In-Kyu
IK
Park
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019187:Cadmium Compounds / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D008164:Luminescent Proteins / Q000737:chemistry* / Q000235:genetics; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045663:Quantum Dots; D017382:Reactive Oxygen Species / Q000378:metabolism; D018036:Selenium Compounds / Q000737:chemistry; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000737:chemistry; D013499:Surface Properties; D017967:Zinc Compounds / Q000737:chemistry; D000097573:Red Fluorescent Protein
D019187:Cadmium Compounds; D008164:Luminescent Proteins; D008823:Micelles; D017319:Photosensitizing Agents; D011108:Polymers; D017382:Reactive Oxygen Species; D018036:Selenium Compounds; D013440:Sulfides; D017967:Zinc Compounds; D000097573:Red Fluorescent Protein; C058667:cadmium selenide; C031238:zinc sulfide
Breast cancer; Intracellular activation; Killer Red; Polymeric micelles; Quantum dot