Limits...
Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells.

Tran TH, Ramasamy T, Choi JY, Nguyen HT, Pham TT, Jeong JH, Ku SK, Choi HG, Yong CS, Kim JO - Int J Nanomedicine (2015)

Bottom Line: The negative surface charge and PEG shell of vehicle remarkably enhanced the blood circulation and physiological activity of DTX-LPH nanoparticles compared with that of free DTX.The nanoparticles were also found to reduce the size of tumors in tumor-bearing xenograft mice.The in vivo anticancer effect of DTX-LPH nanoparticles was further confirmed by the elevated levels of caspase-3 and poly ADP ribose polymerase found in the tumors after treatment.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Yeungnam University, Dae-Dong, South Korea.

ABSTRACT
The attachment of polyethylene glycol (PEG) increases the circulation time of drug-containing nanoparticles; however, this also negatively affects cellular uptake. To overcome this problem, unique lipid polymer hybrid (LPH) nanoparticles were developed with a pH-responsive PEG layer that detached prior to cell uptake. Docetaxel (DTX) was incorporated into the lipid core of the nanoparticles, which was then shielded with the pH-responsive block co-polymer polyethylene glycol-b-polyaspartic acid (PEG-b-PAsp) using a modified emulsion method. The optimized LPH nanoparticles were ~200 nm and had a narrow size distribution. Drug release from DTX-loaded LPH (DTX-LPH) nanoparticles was pH-sensitive, which is beneficial for tumor targeting. More importantly, DTX-LPH nanoparticles were able to effectively induce apoptosis in cancer cells. The negative surface charge and PEG shell of vehicle remarkably enhanced the blood circulation and physiological activity of DTX-LPH nanoparticles compared with that of free DTX. The nanoparticles were also found to reduce the size of tumors in tumor-bearing xenograft mice. The in vivo anticancer effect of DTX-LPH nanoparticles was further confirmed by the elevated levels of caspase-3 and poly ADP ribose polymerase found in the tumors after treatment. Thus, the results suggest that this novel LPH system could be an effective new treatment for cancer.

No MeSH data available.


Related in: MedlinePlus

Protein quantification of p21, p27, and p53 expression in MDA-MB-231 cells by Western blotting after 24 hours incubation of free DTX or DTX-LPH nanoparticles at DTX concentrations of 10 μg/mL.Abbreviations: DTX, docetaxel; DTX-LPH, docetaxel-loaded lipid polymer hybrid.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4552257&req=5

f6-ijn-10-5249: Protein quantification of p21, p27, and p53 expression in MDA-MB-231 cells by Western blotting after 24 hours incubation of free DTX or DTX-LPH nanoparticles at DTX concentrations of 10 μg/mL.Abbreviations: DTX, docetaxel; DTX-LPH, docetaxel-loaded lipid polymer hybrid.

Mentions: Next, we explored the effects of free DTX and DTX-LPH on downstream apoptosis-related protein signaling pathways such as p53, p27, and p21 in MDA-MB-231 cancer cells. The results showed that both DTX and DTX-LPH increased the expression of p53, p27, and p21 (Figure 6). The activation of p53-mediated promotion of apoptosis in tumor cells is an important mechanism of antitumor drugs. We saw that DTX-induced p53 protein expression and DTX-LPH had the strongest effect. The free drug and DTX-LPH also affected induction of the cyclin-dependent kinase inhibitors p21 and p27, which are well known to regulate cell cycle progression during the G1 and S phases.31,32 Enhancements of p53, p27, and p21 expressions suggest that the drug inhibits cancer propagation and induces cell cycle arrest because of its ability to regulate cell apoptosis and cell cycle-related genes.33,34


Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells.

Tran TH, Ramasamy T, Choi JY, Nguyen HT, Pham TT, Jeong JH, Ku SK, Choi HG, Yong CS, Kim JO - Int J Nanomedicine (2015)

Protein quantification of p21, p27, and p53 expression in MDA-MB-231 cells by Western blotting after 24 hours incubation of free DTX or DTX-LPH nanoparticles at DTX concentrations of 10 μg/mL.Abbreviations: DTX, docetaxel; DTX-LPH, docetaxel-loaded lipid polymer hybrid.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4552257&req=5

f6-ijn-10-5249: Protein quantification of p21, p27, and p53 expression in MDA-MB-231 cells by Western blotting after 24 hours incubation of free DTX or DTX-LPH nanoparticles at DTX concentrations of 10 μg/mL.Abbreviations: DTX, docetaxel; DTX-LPH, docetaxel-loaded lipid polymer hybrid.
Mentions: Next, we explored the effects of free DTX and DTX-LPH on downstream apoptosis-related protein signaling pathways such as p53, p27, and p21 in MDA-MB-231 cancer cells. The results showed that both DTX and DTX-LPH increased the expression of p53, p27, and p21 (Figure 6). The activation of p53-mediated promotion of apoptosis in tumor cells is an important mechanism of antitumor drugs. We saw that DTX-induced p53 protein expression and DTX-LPH had the strongest effect. The free drug and DTX-LPH also affected induction of the cyclin-dependent kinase inhibitors p21 and p27, which are well known to regulate cell cycle progression during the G1 and S phases.31,32 Enhancements of p53, p27, and p21 expressions suggest that the drug inhibits cancer propagation and induces cell cycle arrest because of its ability to regulate cell apoptosis and cell cycle-related genes.33,34

Bottom Line: The negative surface charge and PEG shell of vehicle remarkably enhanced the blood circulation and physiological activity of DTX-LPH nanoparticles compared with that of free DTX.The nanoparticles were also found to reduce the size of tumors in tumor-bearing xenograft mice.The in vivo anticancer effect of DTX-LPH nanoparticles was further confirmed by the elevated levels of caspase-3 and poly ADP ribose polymerase found in the tumors after treatment.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Yeungnam University, Dae-Dong, South Korea.

ABSTRACT
The attachment of polyethylene glycol (PEG) increases the circulation time of drug-containing nanoparticles; however, this also negatively affects cellular uptake. To overcome this problem, unique lipid polymer hybrid (LPH) nanoparticles were developed with a pH-responsive PEG layer that detached prior to cell uptake. Docetaxel (DTX) was incorporated into the lipid core of the nanoparticles, which was then shielded with the pH-responsive block co-polymer polyethylene glycol-b-polyaspartic acid (PEG-b-PAsp) using a modified emulsion method. The optimized LPH nanoparticles were ~200 nm and had a narrow size distribution. Drug release from DTX-loaded LPH (DTX-LPH) nanoparticles was pH-sensitive, which is beneficial for tumor targeting. More importantly, DTX-LPH nanoparticles were able to effectively induce apoptosis in cancer cells. The negative surface charge and PEG shell of vehicle remarkably enhanced the blood circulation and physiological activity of DTX-LPH nanoparticles compared with that of free DTX. The nanoparticles were also found to reduce the size of tumors in tumor-bearing xenograft mice. The in vivo anticancer effect of DTX-LPH nanoparticles was further confirmed by the elevated levels of caspase-3 and poly ADP ribose polymerase found in the tumors after treatment. Thus, the results suggest that this novel LPH system could be an effective new treatment for cancer.

No MeSH data available.


Related in: MedlinePlus