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Characterization of 9-nitrocamptothecin liposomes: anticancer properties and mechanisms on hepatocellular carcinoma in vitro and in vivo.

Zheng S, Chang S, Lu J, Chen Z, Xie L, Nie Y, He B, Zou S, Gu Z - PLoS ONE (2011)

Bottom Line: Then we compared the effects of 9NC and 9NC-LP on the proliferation and apoptosis of HepG2, Bel-7402, Hep3B and L02 cells in vitro.Exposure to 9NC-LP led to increased expression of p53, p21, p27, Bax, caspase-3, caspase-8, caspase-9 and apoptosis-inducing factor, mitochondrion-associated 1 and decreased expression of Bcl-2, cyclin E, cyclin A, Cdk2 and cyclin D1.In conclusion, 9NC and 9NC-LP can inhibit HCC growth via cell cycle arrest and induction of apoptosis. 9NC-LP has a more potent anti-tumor effect and fewer side effects in vivo, which means it is a promising reagent for cancer therapy via intravenous administration.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, People's Republic of China.

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is the third most common cause of cancer related mortality worldwide. 9-Nitrocamptothecin (9NC) is a potent topoisomerase-I inhibitor with strong anticancer effect. To increase the solubility and stability, we synthesized a novel 9NC loaded liposomes (9NC-LP) via incorporating 9NC into liposomes. In the present study, we determined the effects of 9NC and 9NC-LP on in vitro and in vivo, and the underlying mechanisms.

Methodology/principal findings: We first analyzed the characteristics of 9NC-LP. Then we compared the effects of 9NC and 9NC-LP on the proliferation and apoptosis of HepG2, Bel-7402, Hep3B and L02 cells in vitro. We also investigated their anticancer properties in nude mice bearing HCC xenograft in vivo. 9NC-LP has a uniform size (around 190 nm) and zeta potential (∼-11 mV), and exhibited a steady sustained-release pattern profile in vitro. Both 9NC and 9NC-LP could cause cell cycle arrest and apoptosis in a dose-dependent and p53-dependent manner. However, this effect was not ubiquitous in all cell lines. Exposure to 9NC-LP led to increased expression of p53, p21, p27, Bax, caspase-3, caspase-8, caspase-9 and apoptosis-inducing factor, mitochondrion-associated 1 and decreased expression of Bcl-2, cyclin E, cyclin A, Cdk2 and cyclin D1. Furthermore, 9NC-LP exhibited a more potent antiproliferative effect and less side effects in vivo. Western blot analysis of the xenograft tumors in nude mice showed similar changes in protein expression in vivo.

Conclusions/significance: In conclusion, 9NC and 9NC-LP can inhibit HCC growth via cell cycle arrest and induction of apoptosis. 9NC-LP has a more potent anti-tumor effect and fewer side effects in vivo, which means it is a promising reagent for cancer therapy via intravenous administration.

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Related in: MedlinePlus

SEM image and in vitro release profile of 9NC loaded liposomes.(A) SEM image of 9NC loaded liposomes. (B) In vitro release profile of 9NC from liposomes in pH 7.4-PBS at 37±1°C by the dialysis method. The results are expressed as mean±SD (n = 3).
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pone-0021064-g001: SEM image and in vitro release profile of 9NC loaded liposomes.(A) SEM image of 9NC loaded liposomes. (B) In vitro release profile of 9NC from liposomes in pH 7.4-PBS at 37±1°C by the dialysis method. The results are expressed as mean±SD (n = 3).

Mentions: The average size of 9NC loaded liposomes before and after lyophilization was 160∼200 nm, with a very narrow size distribution (Table 1). Encapsulation of 9NC slightly increased the size of particles from 160 nm to 190 nm. There was no detectable difference of the zeta potential (∼−11 mV) and encapsulation efficiency (4.5%) of liposomes after lyophilization, which confirmed no degradation or aggregation occurred during the lyophilization and storage. As showed in SEM (Fig. 1A), 9NC encapsulated liposomes was of regular spherical shape, while with smaller size (∼50 nm) than that detected by photon correlation spectroscopy. It should be noted that the difference in the detected sizes is due to the fact that photon correlation spectroscopy gives the hydrodynamic diameter, while SEM shows the shape of dried particles. The in vitro release of the 9NC loaded liposomes was presented in Fig. 1B. The release time of the liposomes could last for 600 minutes and the burst release is not obvious, which implied that the hydrophobic 9NC was successfully encapsulated in the liposomes.


Characterization of 9-nitrocamptothecin liposomes: anticancer properties and mechanisms on hepatocellular carcinoma in vitro and in vivo.

Zheng S, Chang S, Lu J, Chen Z, Xie L, Nie Y, He B, Zou S, Gu Z - PLoS ONE (2011)

SEM image and in vitro release profile of 9NC loaded liposomes.(A) SEM image of 9NC loaded liposomes. (B) In vitro release profile of 9NC from liposomes in pH 7.4-PBS at 37±1°C by the dialysis method. The results are expressed as mean±SD (n = 3).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3111480&req=5

pone-0021064-g001: SEM image and in vitro release profile of 9NC loaded liposomes.(A) SEM image of 9NC loaded liposomes. (B) In vitro release profile of 9NC from liposomes in pH 7.4-PBS at 37±1°C by the dialysis method. The results are expressed as mean±SD (n = 3).
Mentions: The average size of 9NC loaded liposomes before and after lyophilization was 160∼200 nm, with a very narrow size distribution (Table 1). Encapsulation of 9NC slightly increased the size of particles from 160 nm to 190 nm. There was no detectable difference of the zeta potential (∼−11 mV) and encapsulation efficiency (4.5%) of liposomes after lyophilization, which confirmed no degradation or aggregation occurred during the lyophilization and storage. As showed in SEM (Fig. 1A), 9NC encapsulated liposomes was of regular spherical shape, while with smaller size (∼50 nm) than that detected by photon correlation spectroscopy. It should be noted that the difference in the detected sizes is due to the fact that photon correlation spectroscopy gives the hydrodynamic diameter, while SEM shows the shape of dried particles. The in vitro release of the 9NC loaded liposomes was presented in Fig. 1B. The release time of the liposomes could last for 600 minutes and the burst release is not obvious, which implied that the hydrophobic 9NC was successfully encapsulated in the liposomes.

Bottom Line: Then we compared the effects of 9NC and 9NC-LP on the proliferation and apoptosis of HepG2, Bel-7402, Hep3B and L02 cells in vitro.Exposure to 9NC-LP led to increased expression of p53, p21, p27, Bax, caspase-3, caspase-8, caspase-9 and apoptosis-inducing factor, mitochondrion-associated 1 and decreased expression of Bcl-2, cyclin E, cyclin A, Cdk2 and cyclin D1.In conclusion, 9NC and 9NC-LP can inhibit HCC growth via cell cycle arrest and induction of apoptosis. 9NC-LP has a more potent anti-tumor effect and fewer side effects in vivo, which means it is a promising reagent for cancer therapy via intravenous administration.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, People's Republic of China.

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is the third most common cause of cancer related mortality worldwide. 9-Nitrocamptothecin (9NC) is a potent topoisomerase-I inhibitor with strong anticancer effect. To increase the solubility and stability, we synthesized a novel 9NC loaded liposomes (9NC-LP) via incorporating 9NC into liposomes. In the present study, we determined the effects of 9NC and 9NC-LP on in vitro and in vivo, and the underlying mechanisms.

Methodology/principal findings: We first analyzed the characteristics of 9NC-LP. Then we compared the effects of 9NC and 9NC-LP on the proliferation and apoptosis of HepG2, Bel-7402, Hep3B and L02 cells in vitro. We also investigated their anticancer properties in nude mice bearing HCC xenograft in vivo. 9NC-LP has a uniform size (around 190 nm) and zeta potential (∼-11 mV), and exhibited a steady sustained-release pattern profile in vitro. Both 9NC and 9NC-LP could cause cell cycle arrest and apoptosis in a dose-dependent and p53-dependent manner. However, this effect was not ubiquitous in all cell lines. Exposure to 9NC-LP led to increased expression of p53, p21, p27, Bax, caspase-3, caspase-8, caspase-9 and apoptosis-inducing factor, mitochondrion-associated 1 and decreased expression of Bcl-2, cyclin E, cyclin A, Cdk2 and cyclin D1. Furthermore, 9NC-LP exhibited a more potent antiproliferative effect and less side effects in vivo. Western blot analysis of the xenograft tumors in nude mice showed similar changes in protein expression in vivo.

Conclusions/significance: In conclusion, 9NC and 9NC-LP can inhibit HCC growth via cell cycle arrest and induction of apoptosis. 9NC-LP has a more potent anti-tumor effect and fewer side effects in vivo, which means it is a promising reagent for cancer therapy via intravenous administration.

Show MeSH
Related in: MedlinePlus