Enhanced intracellular delivery and improved antitumor efficacy of doxorubicin by sterically stabilized liposomes modified with a synthetic RGD mimetic

Xiong, Xiao-Bing; Huang, Yue; Lü, Wan-Liang; Zhang, Xuan; Zhang, Hua; Nagai, Tsuneji; Zhang, Qiang

doi:10.1016/j.jconrel.2005.03.030

Cited by 192 publications

(106 citation statements)

References 30 publications

Supporting

Mentioning

100

Contrasting

Order By: Relevance

“…TK3 can be linked to a tumor-specific target moiety such as RGD sequence that has been successfully used for the delivery of a short peptide (20,21). It can be also delivered to the tumor site by ''passive tumor targeting'' with the help of particles that can carry TK3 by making physical complex or by chemical conjugation (22 -25).…”

Section: Discussionmentioning

confidence: 99%

Antitumor effect of a transducible fusogenic peptide releasing multiple proapoptotic peptides by caspase-3

Kwon

Nam

Park

et al. 2008

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

We have designed a novel peptide, TK3, composed of three functional domains, a protein transduction domain, a TAT followed by three tandem repeats of a proapoptotic peptide, and a caspase-3 cleavage site, (KLAKLAK) 2 -DEVD. TK3 was able to transduce into cells and then activate caspase-3, which in turn cleaved TK3 to release additional (KLAKLAK) 2 peptides. (KLAKLAK) 2 was well transduced by TAT into tumor cells and was able to induce apoptosis in vitro and in vivo. TK3 also induced apoptosis and inhibited angiogenesis in endothelial cells. Further, direct injection of TK3 into established B16F10 melanoma tumors in C57BL/6 mice resulted in almost complete inhibition of the tumor growth. These results suggest that TK3 could be beneficial for the treatment of accessible tumors and used as an adjuvant for cancer therapy. [Mol Cancer Ther 2008;7(6):1514 -22]

show abstract

Section: Discussionmentioning

confidence: 99%

Antitumor effect of a transducible fusogenic peptide releasing multiple proapoptotic peptides by caspase-3

Kwon

Nam

Park

et al. 2008

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…In order to increase therapeutic efficacy of liposomal formulation of anti-cancer drug, polyethyleneglycol (PEG)-coated liposomes for prolongation of circulation half-life time or cancer cell-targetable liposomes having a cancer cell specific motifs have been studied. [ 3 ] Anthracycline drugs including doxorubicin (DOX) are known to readily intercalate into DNA strands [ 4 ] and many studies have shown that DOX preferentially accumulates into the nuclear compartment of cells. [ 5,6 ] In this study, an anthracycline drug, DOX, was conjugated to the end-group of carboxylated phospholipids.…”

Section: Introductionmentioning

confidence: 99%

Anticancer Drug‐Phospholipid Conjugate for Enhancement of Intracellular Drug Delivery

Hwang¹,

Han²,

Song³

et al. 2007

Macromolecular Symposia

View full text Add to dashboard Cite

SummaryTumor specific delivery of anti-cancer drugs is one of the major challenges faced by drug development processes. In this study, we prepared a doxorubicin (DOX)-conjugated liposome (DCL) by incorporating the newly synthesized DSPE-PEG2000-DOX (DPD) into liposomes as a lipid component and tested its anti-tumor activity in vivo. DPD was synthesized by coupling DOX to DSPE-PEG2000-COOH via amide linkage and the chemical structure of resulting DPD was confirmed by 1 H-NMR analysis. DCL having liposome size of 130 nm was prepared through thin film cast-hydration method. DCL was found to have significantly higher cellular uptake than conventional liposomes as confirmed by flow cytometry analysis. Anti-tumor activity of DCL against murine B16F10 melanoma tumor-bearing mice revealed that DCL inhibits tumor growth more efficiently than the conventional liposomes, presumably attributed to DOX mediated endocytosis process.

show abstract

“…Liposomal delivery has been shown to reduce cardiac toxicity of doxorubicin (Perez et al, 2002). Targeted liposomes can be synthesized by incorporating a tumor cell-selective ligand, such as antibodies, transferrin and folic acid (Gabizon et al, 2004;Lukyanov et al, 2004;Pan et al 2007;Wu et al, 2006a;Xiong et al, 2005), via a lipophilic anchor, typically consisting of a derivative of distearoylphosphatidylethanolamine (DSPE). …”

mentioning

confidence: 99%

Synthesis and evaluation of a novel ligand for folate-mediated targeting liposomes

Xiang

et al. 2008

International Journal of Pharmaceutics

112

View full text Add to dashboard Cite

Folate receptors (FRs) have been identified as cellular surface markers for cancer and leukemia. Liposomes containing lipophilic derivatives of folate have been shown to effectively target FRexpressing cells. Here, we report the synthesis of a novel lipophilic folate derivative, folatepolyethylene glycol-cholesterol hemisuccinate (F-PEG-CHEMS), and its evaluation as a targeting ligand for liposomal doxorubicin (L-DOX) in FR-expressing cells. Liposomes containing F-PEG-CHEMS, with a mean diameter of 120±20nm, were synthesized by polycarbonate membrane extrusion and were shown to have excellent colloidal stability. The liposomes were taken up selectively by KB cells, which overexpress FR-α. Compared to folate-PEG-cholesterol (F-PEGChol), which contains a carbamate linkage, F-PEG-CHEMS better retained its FR-targeting activity during prolonged storage. In addition, F-PEG-CHEMS containing liposomes loaded with DOX (F-L-DOX) showed greater cytotoxicity (IC 50 =10.0μM) than non-targeted control L-DOX (IC 50 = 57.5μM) in KB cells. In ICR mice, both targeted and non-targeted liposomes exhibited long circulation properties, although F-L-DOX (t 1/2 = 12.34 hr) showed more rapid plasma clearance than L-DOX (t 1/2 = 17.10 hr). These results suggest that F-PEG-CHEMS is effective as a novel ligand for the synthesis of FR-targeted liposomes. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. , 2001; Momot et al., 2003;Papahadjopoulos et al., 1991) and is facilitated by plasma protein opsonization. Incorporation of polyethylene glycol (PEG) coating on liposomes has been shown to reduce the rate of RES clearance of liposomes Fritze et al., 2006; Momot et al., 2003;Papahadjopoulos et al., 1991). Liposomal delivery has been shown to reduce cardiac toxicity of doxorubicin (Perez et al., 2002). Targeted liposomes can be synthesized by incorporating a tumor cell-selective ligand, such as antibodies, transferrin and folic acid (Gabizon et al., 2004;Lukyanov et al., 2004;Pan et al. 2007;Wu et al., 2006a;Xiong et al., 2005), via a lipophilic anchor, typically consisting of a derivative of distearoylphosphatidylethanolamine (DSPE). NIH Public AccessMembrane folate receptors (FRs), including FR-α and FR-β, are glycosylphosphatidylinositol (GPI)-anchored glycoproteins. FR-α expression is amplified in over 90% of ovarian carcinomas and at varying frequencies in other epithelial cancers. Meanwhile, FR-β is expressed in a non-functional form in neutrophils and in a functional form in activated macrophages and in myeloid leukemias (Elwood et al., 1989;McHugh et al., 1979). In contrast, most normal...

show abstract

Enhanced intracellular delivery and improved antitumor efficacy of doxorubicin by sterically stabilized liposomes modified with a synthetic RGD mimetic

Cited by 192 publications

References 30 publications

Antitumor effect of a transducible fusogenic peptide releasing multiple proapoptotic peptides by caspase-3

Antitumor effect of a transducible fusogenic peptide releasing multiple proapoptotic peptides by caspase-3

Anticancer Drug‐Phospholipid Conjugate for Enhancement of Intracellular Drug Delivery

Synthesis and evaluation of a novel ligand for folate-mediated targeting liposomes

Contact Info

Product

Resources

About