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Improved anti-glioblastoma efficacy by IL-13Rα2 mediated copolymer nanoparticles loaded with paclitaxel.

Wang B, Lv L, Wang Z, Jiang Y, Lv W, Liu X, Wang Z, Zhao Y, Xin H, Xu Q - Sci Rep (2015)

Bottom Line: The in vitro anti-proliferation evaluation showed that the IC50 were 146 ng/ml and 349 ng/ml of Pep-NP-PTX and NP-PTX, respectively.The in vivo fluorescent image results indicated that Pep-NP had higher specificity and efficiency in intracranial tumor accumulation.Pep-NP-PTX could improve the anti-glioma efficacy with a median survival time of 32 days, which was significantly longer than that of PTX-NP (23 days) and Taxol(®) (22 days).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.

ABSTRACT
Glioma presents one of the most malignant brain tumors, and the therapeutic effect is often limited due to the existence of brain tumor barrier. Based on interleukin-13 receptor α2 (IL-13Rα2) over-expression on glioma cell, it was demonstrated to be a potential receptor for glioma targeting. In this study, Pep-1-conjugated PEGylated nanoparticles loaded with paclitaxel (Pep-NP-PTX) were developed as a targeting drug delivery system for glioma treatment. The Pep-NP-PTX presented satisfactory size of 95.78 nm with narrow size distribution. Compared with NP-PTX, Pep-NP-PTX exhibited significantly enhanced cellular uptake in C6 cells (p < 0.001). The in vitro anti-proliferation evaluation showed that the IC50 were 146 ng/ml and 349 ng/ml of Pep-NP-PTX and NP-PTX, respectively. The in vivo fluorescent image results indicated that Pep-NP had higher specificity and efficiency in intracranial tumor accumulation. Following intravenous administration, Pep-NP-PTX could enhance the distribution of PTX in vivo glioma section, 1.98, 1.91 and 1.53-fold over that of NP-PTX group after 0.5, 1 and 4 h, respectively. Pep-NP-PTX could improve the anti-glioma efficacy with a median survival time of 32 days, which was significantly longer than that of PTX-NP (23 days) and Taxol(®) (22 days). In conclusion, Pep-NP-PTX is a potential targeting drug delivery system for glioma treatment.

No MeSH data available.


Related in: MedlinePlus

In vitro viability of C6 cells of Cremophor EL and blank nanoparticles at concentration ranging from 0.1 to 1000 μg/mL at 72 h (A); In vitro cytotoxicity of Taxol® and PTX-loading nanoparticles at various concentrations at 72 h (B). Data represented mean ± SD (n = 3). **p < 0.01, ***p < 0.001 significantly lower than that of NP-PTX.
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f4: In vitro viability of C6 cells of Cremophor EL and blank nanoparticles at concentration ranging from 0.1 to 1000 μg/mL at 72 h (A); In vitro cytotoxicity of Taxol® and PTX-loading nanoparticles at various concentrations at 72 h (B). Data represented mean ± SD (n = 3). **p < 0.01, ***p < 0.001 significantly lower than that of NP-PTX.

Mentions: The in vitro cell cytotoxicity of different formulations was evaluated on C6 cells by using MTT method. As shown in Fig. 4A, the cytotoxicity of Cremophor EL was obviously higher than that of nanoparticles when the incubation concentration was more than 10 μg/mL. However, blank NP and Pep-NP did not show obvious cytotoxicity at concentrations ranged from 0.1 μg/mL to 1000 μg/mL. These results suggested that blank NP and Pep-NP were not toxic to C6 cells probably due to the biocompatibility of the block polymers.


Improved anti-glioblastoma efficacy by IL-13Rα2 mediated copolymer nanoparticles loaded with paclitaxel.

Wang B, Lv L, Wang Z, Jiang Y, Lv W, Liu X, Wang Z, Zhao Y, Xin H, Xu Q - Sci Rep (2015)

In vitro viability of C6 cells of Cremophor EL and blank nanoparticles at concentration ranging from 0.1 to 1000 μg/mL at 72 h (A); In vitro cytotoxicity of Taxol® and PTX-loading nanoparticles at various concentrations at 72 h (B). Data represented mean ± SD (n = 3). **p < 0.01, ***p < 0.001 significantly lower than that of NP-PTX.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4645113&req=5

f4: In vitro viability of C6 cells of Cremophor EL and blank nanoparticles at concentration ranging from 0.1 to 1000 μg/mL at 72 h (A); In vitro cytotoxicity of Taxol® and PTX-loading nanoparticles at various concentrations at 72 h (B). Data represented mean ± SD (n = 3). **p < 0.01, ***p < 0.001 significantly lower than that of NP-PTX.
Mentions: The in vitro cell cytotoxicity of different formulations was evaluated on C6 cells by using MTT method. As shown in Fig. 4A, the cytotoxicity of Cremophor EL was obviously higher than that of nanoparticles when the incubation concentration was more than 10 μg/mL. However, blank NP and Pep-NP did not show obvious cytotoxicity at concentrations ranged from 0.1 μg/mL to 1000 μg/mL. These results suggested that blank NP and Pep-NP were not toxic to C6 cells probably due to the biocompatibility of the block polymers.

Bottom Line: The in vitro anti-proliferation evaluation showed that the IC50 were 146 ng/ml and 349 ng/ml of Pep-NP-PTX and NP-PTX, respectively.The in vivo fluorescent image results indicated that Pep-NP had higher specificity and efficiency in intracranial tumor accumulation.Pep-NP-PTX could improve the anti-glioma efficacy with a median survival time of 32 days, which was significantly longer than that of PTX-NP (23 days) and Taxol(®) (22 days).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.

ABSTRACT
Glioma presents one of the most malignant brain tumors, and the therapeutic effect is often limited due to the existence of brain tumor barrier. Based on interleukin-13 receptor α2 (IL-13Rα2) over-expression on glioma cell, it was demonstrated to be a potential receptor for glioma targeting. In this study, Pep-1-conjugated PEGylated nanoparticles loaded with paclitaxel (Pep-NP-PTX) were developed as a targeting drug delivery system for glioma treatment. The Pep-NP-PTX presented satisfactory size of 95.78 nm with narrow size distribution. Compared with NP-PTX, Pep-NP-PTX exhibited significantly enhanced cellular uptake in C6 cells (p < 0.001). The in vitro anti-proliferation evaluation showed that the IC50 were 146 ng/ml and 349 ng/ml of Pep-NP-PTX and NP-PTX, respectively. The in vivo fluorescent image results indicated that Pep-NP had higher specificity and efficiency in intracranial tumor accumulation. Following intravenous administration, Pep-NP-PTX could enhance the distribution of PTX in vivo glioma section, 1.98, 1.91 and 1.53-fold over that of NP-PTX group after 0.5, 1 and 4 h, respectively. Pep-NP-PTX could improve the anti-glioma efficacy with a median survival time of 32 days, which was significantly longer than that of PTX-NP (23 days) and Taxol(®) (22 days). In conclusion, Pep-NP-PTX is a potential targeting drug delivery system for glioma treatment.

No MeSH data available.


Related in: MedlinePlus