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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

The representative in vivo (A) and ex vivo (B) images of C26 tumor-bearing mice 24 h after injection of DID-loaded liposomes. (C) The CLSM images of tumor frozen sections from C26 tumor-bearing mice receiving different DID-loaded liposomes.
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f0025: The representative in vivo (A) and ex vivo (B) images of C26 tumor-bearing mice 24 h after injection of DID-loaded liposomes. (C) The CLSM images of tumor frozen sections from C26 tumor-bearing mice receiving different DID-loaded liposomes.

Mentions: To estimate the in vivo liposomal delivery to tumors, whole body optical imaging and ex vivo organ imaging were taken using the Bio-Real in vivo imaging system. Fig. 5A shows that 24 h after injection of different liposomes, fluorescence intensity in the tumors of CL-R8-LP-treated mice were significantly higher than that of R8-treated mice, and even slightly stronger than that of PEG-LP-treated mice. These findings were consistent with the results of ex vivo organ imaging at 24 h (Fig. 5B). In addition, R8-LP was mostly distributed in liver, spleen and lung, whereas CL-R8-LP and PEG-LP distributions in these organs were decreased significantly (Fig. 5B). To further explore the delivery characteristics of CL-R8-LP and PEG-LP liposomes into cells after the sufficient tumor accumulation, tumor sections from C26 tumor-bearing mice receiving different liposomes were observed by CLSM. Fluorescence intensities in the tumor sections of CL-R8-LP (with Cys) treated mice were much higher than those of PEG-Lip and CL-R8-LP (without Cys) treated mice.


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)

The representative in vivo (A) and ex vivo (B) images of C26 tumor-bearing mice 24 h after injection of DID-loaded liposomes. (C) The CLSM images of tumor frozen sections from C26 tumor-bearing mice receiving different DID-loaded liposomes.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0025: The representative in vivo (A) and ex vivo (B) images of C26 tumor-bearing mice 24 h after injection of DID-loaded liposomes. (C) The CLSM images of tumor frozen sections from C26 tumor-bearing mice receiving different DID-loaded liposomes.
Mentions: To estimate the in vivo liposomal delivery to tumors, whole body optical imaging and ex vivo organ imaging were taken using the Bio-Real in vivo imaging system. Fig. 5A shows that 24 h after injection of different liposomes, fluorescence intensity in the tumors of CL-R8-LP-treated mice were significantly higher than that of R8-treated mice, and even slightly stronger than that of PEG-LP-treated mice. These findings were consistent with the results of ex vivo organ imaging at 24 h (Fig. 5B). In addition, R8-LP was mostly distributed in liver, spleen and lung, whereas CL-R8-LP and PEG-LP distributions in these organs were decreased significantly (Fig. 5B). To further explore the delivery characteristics of CL-R8-LP and PEG-LP liposomes into cells after the sufficient tumor accumulation, tumor sections from C26 tumor-bearing mice receiving different liposomes were observed by CLSM. Fluorescence intensities in the tumor sections of CL-R8-LP (with Cys) treated mice were much higher than those of PEG-Lip and CL-R8-LP (without Cys) treated mice.

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