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A detachable coating of cholesterol-anchored PEG improves tumor targeting of cell-penetrating peptide-modified liposomes.

Tang J, Zhang L, Fu H, Kuang Q, Gao H, Zhang Z, He Q - Acta Pharm Sin B (2014)

Bottom Line: Cell-penetrating peptides (CPPs) have been widely used to enhance the membrane translocation of various carriers for many years, but the non-specificity of CPPs seriously limits their utility in vivo.Following optimization of the formulation, the in vitro and in vivo properties of the co-modified liposome were evaluated.The present results demonstrate that the combination of cholestervsitive PEG and CPPs is an ideal alternative for the application of CPP-modified carriers in vivo.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.

ABSTRACT
Cell-penetrating peptides (CPPs) have been widely used to enhance the membrane translocation of various carriers for many years, but the non-specificity of CPPs seriously limits their utility in vivo. In this study, cholesterol-anchored, reduction-sensitive PEG (first synthesized by our laboratory) was applied to develop a co-modified liposome with improved tumor targeting. Following optimization of the formulation, the in vitro and in vivo properties of the co-modified liposome were evaluated. The co-modified liposome had a much lower cellular uptake and tumor spheroid uptake, but a much higher tumor accumulation compared to CPP-modified liposome, indicating the non-specific penetration of CPPs could be attenuated by the outer PEG coating. With the addition of exogenous reducing agent, both the in vitro and in vivo cellular uptake was markedly increased, demonstrating that the reduction-sensitive PEG coating achieved a controllable detachment from the surface of liposomes and did not affect the penetrating abilities of CPPs. The present results demonstrate that the combination of cholestervsitive PEG and CPPs is an ideal alternative for the application of CPP-modified carriers in vivo.

No MeSH data available.


Related in: MedlinePlus

Fluorescence intensity of C26 cells measured by flow cytometer after incubated with different CFPE-labeled liposomes at 37 °C for 4 h. Data represent the mean±SD (n=3). ***P<0.001; N.S.=no significant difference.
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f0015: Fluorescence intensity of C26 cells measured by flow cytometer after incubated with different CFPE-labeled liposomes at 37 °C for 4 h. Data represent the mean±SD (n=3). ***P<0.001; N.S.=no significant difference.

Mentions: The quantitative results of cellular uptake were consistent with the results of fluorescence imaging. As shown in Fig. 3, the uptake amount of CL-R8-LP in the presence of Cys was 21.6 and 66.5 times higher than that of CL-R8-LP in the absence of Cys and PEG-LP respectively, and was comparable to the cellular uptake of R8-LP.


A detachable coating of cholesterol-anchored PEG improves tumor targeting of cell-penetrating peptide-modified liposomes.

Tang J, Zhang L, Fu H, Kuang Q, Gao H, Zhang Z, He Q - Acta Pharm Sin B (2014)

Fluorescence intensity of C26 cells measured by flow cytometer after incubated with different CFPE-labeled liposomes at 37 °C for 4 h. Data represent the mean±SD (n=3). ***P<0.001; N.S.=no significant difference.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590295&req=5

f0015: Fluorescence intensity of C26 cells measured by flow cytometer after incubated with different CFPE-labeled liposomes at 37 °C for 4 h. Data represent the mean±SD (n=3). ***P<0.001; N.S.=no significant difference.
Mentions: The quantitative results of cellular uptake were consistent with the results of fluorescence imaging. As shown in Fig. 3, the uptake amount of CL-R8-LP in the presence of Cys was 21.6 and 66.5 times higher than that of CL-R8-LP in the absence of Cys and PEG-LP respectively, and was comparable to the cellular uptake of R8-LP.

Bottom Line: Cell-penetrating peptides (CPPs) have been widely used to enhance the membrane translocation of various carriers for many years, but the non-specificity of CPPs seriously limits their utility in vivo.Following optimization of the formulation, the in vitro and in vivo properties of the co-modified liposome were evaluated.The present results demonstrate that the combination of cholestervsitive PEG and CPPs is an ideal alternative for the application of CPP-modified carriers in vivo.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.

ABSTRACT
Cell-penetrating peptides (CPPs) have been widely used to enhance the membrane translocation of various carriers for many years, but the non-specificity of CPPs seriously limits their utility in vivo. In this study, cholesterol-anchored, reduction-sensitive PEG (first synthesized by our laboratory) was applied to develop a co-modified liposome with improved tumor targeting. Following optimization of the formulation, the in vitro and in vivo properties of the co-modified liposome were evaluated. The co-modified liposome had a much lower cellular uptake and tumor spheroid uptake, but a much higher tumor accumulation compared to CPP-modified liposome, indicating the non-specific penetration of CPPs could be attenuated by the outer PEG coating. With the addition of exogenous reducing agent, both the in vitro and in vivo cellular uptake was markedly increased, demonstrating that the reduction-sensitive PEG coating achieved a controllable detachment from the surface of liposomes and did not affect the penetrating abilities of CPPs. The present results demonstrate that the combination of cholestervsitive PEG and CPPs is an ideal alternative for the application of CPP-modified carriers in vivo.

No MeSH data available.


Related in: MedlinePlus