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Small molecule PZL318: forming fluorescent nanoparticles capable of tracing their interactions with cancer cells and activated platelets, slowing tumor growth and inhibiting thrombosis.

Li S, Wang Y, Wang F, Wang Y, Zhang X, Zhao M, Feng Q, Wu J, Zhao S, Wu W, Peng S - Int J Nanomedicine (2015)

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus

Confocal image of PZL318 at 4°C.Abbreviation: min, minutes.
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f8-ijn-10-5273: Confocal image of PZL318 at 4°C.Abbreviation: min, minutes.

Mentions: To know whether the endocytosis leads to PZL318 nanoparticles entering into cancer cells, HeLa cells were cultured with 40 μM of PZL318 at 4°C for 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 360 minutes. In contrast to the confocal images of HeLa cells cultured with 40 μM of PZL318 at 37°C (Figure 7), the confocal images of HeLa cells cultured with 40 μM of PZL318 at 4°C show no blue fluorescence (Figure 8), suggesting that the endocytosis is the mechanism underlying the PZL318 nanoparticles entering the cancer cells.


Small molecule PZL318: forming fluorescent nanoparticles capable of tracing their interactions with cancer cells and activated platelets, slowing tumor growth and inhibiting thrombosis.

Li S, Wang Y, Wang F, Wang Y, Zhang X, Zhao M, Feng Q, Wu J, Zhao S, Wu W, Peng S - Int J Nanomedicine (2015)

Confocal image of PZL318 at 4°C.Abbreviation: min, minutes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554418&req=5

f8-ijn-10-5273: Confocal image of PZL318 at 4°C.Abbreviation: min, minutes.
Mentions: To know whether the endocytosis leads to PZL318 nanoparticles entering into cancer cells, HeLa cells were cultured with 40 μM of PZL318 at 4°C for 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 360 minutes. In contrast to the confocal images of HeLa cells cultured with 40 μM of PZL318 at 37°C (Figure 7), the confocal images of HeLa cells cultured with 40 μM of PZL318 at 4°C show no blue fluorescence (Figure 8), suggesting that the endocytosis is the mechanism underlying the PZL318 nanoparticles entering the cancer cells.

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus