Limits...
Peptide-mediated liposomal drug delivery system targeting tumor blood vessels in anticancer therapy.

Wu HC, Chang DK - J Oncol (2010)

Bottom Line: Solid tumors are known to recruit new blood vessels to support their growth.These therapies hold the promise of high efficacy and low toxicity.One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan.

ABSTRACT
Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

No MeSH data available.


Related in: MedlinePlus

Generation of peptide-conjugated liposomes targeting tumor blood vessels. A single lipid bilayer membrane separates an internal aqueous compartment from the external medium. Doxorubicin was encapsulated in the internal compartment. Drug molecules are tightly packed (10,000 to 15,000 molecules per liposome) in a gel phase. Tumor-homing peptide ligands were coupled to NHS-PEG-DSPE [N-hydroxysuccinimido-carboxyl-polyethylene glycol-derived distearoylphosphatidylethanolamine] in a 1 : 1.5 molar ratio [13, 14, 50]. The reaction was completed and confirmed by quantifying the remaining amino groups using TNBS (Trinitrobenzenesulfonate) reagent [51]. Peptidyl-PEG-DSPE was transferred to preformed liposomes after coincubation at a temperature above the transition temperature of the lipid bilayer [52]. There were 500 peptide molecules per liposome [53]. The mean diameter of the targeting liposome is approximately 75 nm [2, 13].
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2864512&req=5

fig2: Generation of peptide-conjugated liposomes targeting tumor blood vessels. A single lipid bilayer membrane separates an internal aqueous compartment from the external medium. Doxorubicin was encapsulated in the internal compartment. Drug molecules are tightly packed (10,000 to 15,000 molecules per liposome) in a gel phase. Tumor-homing peptide ligands were coupled to NHS-PEG-DSPE [N-hydroxysuccinimido-carboxyl-polyethylene glycol-derived distearoylphosphatidylethanolamine] in a 1 : 1.5 molar ratio [13, 14, 50]. The reaction was completed and confirmed by quantifying the remaining amino groups using TNBS (Trinitrobenzenesulfonate) reagent [51]. Peptidyl-PEG-DSPE was transferred to preformed liposomes after coincubation at a temperature above the transition temperature of the lipid bilayer [52]. There were 500 peptide molecules per liposome [53]. The mean diameter of the targeting liposome is approximately 75 nm [2, 13].

Mentions: Peptide-conjugated liposomes have three main components: anticancer drug, a liposome carrier, and targeting peptide (Figure 2). Remote loading methods such as the ammonium sulfate method [13, 79] and the pH gradient method [80] can encapsulate weak bases such as doxorubicin or vinorelbine into the liposomes with more than 95% efficiency. Schedule-dependent drugs such as vinca alkaloids, topotecan, and 5-fluorouracil are also potential candidates for liposomal delivery because they can extend the time when cancer cells are exposed to therapeutic levels of the drug.


Peptide-mediated liposomal drug delivery system targeting tumor blood vessels in anticancer therapy.

Wu HC, Chang DK - J Oncol (2010)

Generation of peptide-conjugated liposomes targeting tumor blood vessels. A single lipid bilayer membrane separates an internal aqueous compartment from the external medium. Doxorubicin was encapsulated in the internal compartment. Drug molecules are tightly packed (10,000 to 15,000 molecules per liposome) in a gel phase. Tumor-homing peptide ligands were coupled to NHS-PEG-DSPE [N-hydroxysuccinimido-carboxyl-polyethylene glycol-derived distearoylphosphatidylethanolamine] in a 1 : 1.5 molar ratio [13, 14, 50]. The reaction was completed and confirmed by quantifying the remaining amino groups using TNBS (Trinitrobenzenesulfonate) reagent [51]. Peptidyl-PEG-DSPE was transferred to preformed liposomes after coincubation at a temperature above the transition temperature of the lipid bilayer [52]. There were 500 peptide molecules per liposome [53]. The mean diameter of the targeting liposome is approximately 75 nm [2, 13].
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2864512&req=5

fig2: Generation of peptide-conjugated liposomes targeting tumor blood vessels. A single lipid bilayer membrane separates an internal aqueous compartment from the external medium. Doxorubicin was encapsulated in the internal compartment. Drug molecules are tightly packed (10,000 to 15,000 molecules per liposome) in a gel phase. Tumor-homing peptide ligands were coupled to NHS-PEG-DSPE [N-hydroxysuccinimido-carboxyl-polyethylene glycol-derived distearoylphosphatidylethanolamine] in a 1 : 1.5 molar ratio [13, 14, 50]. The reaction was completed and confirmed by quantifying the remaining amino groups using TNBS (Trinitrobenzenesulfonate) reagent [51]. Peptidyl-PEG-DSPE was transferred to preformed liposomes after coincubation at a temperature above the transition temperature of the lipid bilayer [52]. There were 500 peptide molecules per liposome [53]. The mean diameter of the targeting liposome is approximately 75 nm [2, 13].
Mentions: Peptide-conjugated liposomes have three main components: anticancer drug, a liposome carrier, and targeting peptide (Figure 2). Remote loading methods such as the ammonium sulfate method [13, 79] and the pH gradient method [80] can encapsulate weak bases such as doxorubicin or vinorelbine into the liposomes with more than 95% efficiency. Schedule-dependent drugs such as vinca alkaloids, topotecan, and 5-fluorouracil are also potential candidates for liposomal delivery because they can extend the time when cancer cells are exposed to therapeutic levels of the drug.

Bottom Line: Solid tumors are known to recruit new blood vessels to support their growth.These therapies hold the promise of high efficacy and low toxicity.One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan.

ABSTRACT
Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

No MeSH data available.


Related in: MedlinePlus