Photosensitizer-mediated mitochondria-targeting nanosized drug carriers: Subcellular targeting, therapeutic, and imaging potentials.
Mitochondria-targeting drug carriers have considerable potential because of the presence of many molecular drug targets in the mitochondria and their pivotal roles in cellular viability, metabolism, maintenance, and death. To compare the mitochondria-targeting abilities of triphenylphosphonium (TPP) and pheophorbide a (PhA) in nanoparticles (NPs), this study prepared mitochondria-targeting NPs using mixtures of methoxy poly(ethylene glycol)-(SS-PhA)2[mPEG-(SS-PhA)2or PPA] and TPP-b-poly(ε-caprolactone)-b-TPP [TPP-b-PCL-b-TPP or TPCL], which were designated PPAn-TPCL4-n(0≤n≤4) NPs. With increasing TPCL content, the formed PPAn-TPCL4-nNPs decreased in size from 33nm to 18nm and increased in terms of positive zeta-potentials from -12mV to 33mV. Although the increased TPCL content caused some dark toxicity of the PPAn-TPCL4-nNPs due to the intrinsic positive character of TPCL, the NPs showed strong light-induced killing effects in tumor cells. In addition, the mitochondrial distribution of the PPAn-TPCL4-nNPs was analyzed and imaged by flow cytometry and confocal microscopy, respectively. Thus, the PhA-containing NPs specifically targeted the mitochondria, and light stimulation caused PhA-mediated therapeutic effects and imaging functions. Expanding the capabilities of these nanocarriers by incorporating other drugs should enable multiple potential applications (e.g., targeting, therapy, and imaging) for combination and synergistic treatments.
Department of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 14662, Republic of Korea.
Yeon Su
YS
Choi
Department of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 14662, Republic of Korea.
Kiyoon
K
Kwon
Department of Polymer Science and Engineering, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Republic of Korea.
Kwonhyeok
K
Yoon
Department of Polymer Science and Engineering, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Republic of Korea. Electronic address: khuh@cnu.ac.kr.
Kang Moo
KM
Huh
Department of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 14662, Republic of Korea. Electronic address: hckang@catholic.ac.kr.
Han Chang
HC
Kang
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002734:Chlorophyll / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003952:Diagnostic Imaging / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000032:analysis / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
D004337:Drug Carriers; D009943:Organophosphorus Compounds; D017319:Photosensitizing Agents; D011091:Polyesters; C521096:triphenylphosphonium methylide; D002734:Chlorophyll; C016240:polycaprolactone; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; C032623:pheophorbide a
Drug delivery; Mitochondrial targeting; Pheophorbide a; Photosensitizer; Triphenylphosphonium