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已发表论文
小分子 PZL318：形成荧光纳米粒子，能够跟踪其与癌细胞和活化血小板之间的相互作用，减缓肿瘤生长，并抑制血栓形成
Authors Li S, Wang Y, Wang F, Wang Y, Zhang X, Zhao M, Feng Q, Wu J, Zhao S, Wu W, Peng S
Received 6 May 2015
Accepted for publication 13 June 2015
Published 24 August 2015 Volume 2015:10 Pages 5273—5292
DOI http://dx.doi.org/10.2147/IJN.S88052
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Chang Liu
Peer reviewer comments 3
Editor who approved publication: Professor Thomas J Webster
Abstract: 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.
Keywords: nanoparticles, cancer target, sP-selectin, nanomechanism, action mechanism, fluorescent tracer
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.
Keywords: nanoparticles, cancer target, sP-selectin, nanomechanism, action mechanism, fluorescent tracer
