Small molecule PZL318: forming fluorescent nanoparticles capable of tracing their interactions with cancer cells and activated platelets, slowing tumor growth and inhibiting thrombosis.
Low selectivity of chemotherapy correlates with poor outcomes of cancer patients. To improve this issue, a novel agent, N-(1-[3-methoxycarbonyl-4-hydroxyphenyl]-β-carboline-3-carbonyl)-Trp-Lys-OBzl (PZL318), was reported here. The transmission electron microscopy, scanning electron microscopy, and atomic force microscopy images demonstrated that PZL318 can form nanoparticles. Fluorescent and confocal images visualized that PZL318 formed fluorescent nanoparticles capable of targeting cancer cells and tracing their interactions with cancer cells. In vitro, 40 μM of PZL318 inhibited the proliferation of tumorigenic cells, but not nontumorigenic cells. In vivo, 10 nmol/kg of PZL318 slowed the tumor growth of S180 mice and alleviated the thrombosis of ferric chloride-treated ICR mice, while 100 μmol/kg of PZL318 did not injure healthy mice and they exhibited no liver toxicity. By analyzing Fourier transform-mass spectrometry and rotating-frame Overhauser spectroscopy (ROESY) two-dimensional nuclear magnetic resonance spectra, the chemical mechanism of PZL318-forming trimers and nanoparticles was explored. By using mesoscale simulation, a nanoparticle of 3.01 nm in diameter was predicted containing 13 trimers. Scavenging free radicals, downregulating sP-selectin expression and intercalating toward DNA were correlated with the antitumor mechanism of PZL318.
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing Laboratory of Biomedical Materials, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People's Republic of China.
Shan
S
Li
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing Laboratory of Biomedical Materials, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People's Republic of China.
Yuji
Y
Wang
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing Laboratory of Biomedical Materials, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People's Republic of China.
Feng
F
Wang
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing Laboratory of Biomedical Materials, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People's Republic of China.
Yaonan
Y
Wang
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing Laboratory of Biomedical Materials, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People's Republic of China.
Xiaoyi
X
Zhang
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing Laboratory of Biomedical Materials, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People's Republic of China ; Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ming
M
Zhao
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing Laboratory of Biomedical Materials, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People's Republic of China.
Qiqi
Q
Feng
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing Laboratory of Biomedical Materials, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People's Republic of China.
Jianhui
J
Wu
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing Laboratory of Biomedical Materials, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People's Republic of China.
Shurui
S
Zhao
College of Basic Medicine of Capital Medical University, Beijing, People's Republic of China.
Wei
W
Wu
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing Laboratory of Biomedical Materials, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People's Republic of China.
Shiqi
S
Peng
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D002243:Carbolines / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002712:Chlorides / Q000737:chemistry; D002942:Circular Dichroism; D004151:Dipeptides / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017550:Spectroscopy, Fourier Transform Infrared; D013927:Thrombosis; D014783:Viscosity
D002243:Carbolines; D002712:Chlorides; D004151:Dipeptides; D005290:Ferric Compounds; D005456:Fluorescent Dyes; C000610285:PZL318; C024555:ferric chloride
action mechanism; cancer target; fluorescent tracer; nanomechanism; nanoparticles; sP-selectin