Experimental anticancer therapy with vascular-disruptive peptide and liposome-entrapped chemotherapeutic agent

Vasculature is essential for the sustained growth of solid tumors and metastases. Tumor cells surviving vascular-disruptive therapeutic intervention (especially those present at the tumor rim) can contribute to tumor regrowth. The aim was to strengthen, by carrier-mediated delivery of a chemotherapeutic, the curative effects of a bifunctional anti-vascular oligopeptide capable of inducing vascular shutdown and tumor shrinkage. For the in vitro experiments and animal therapy, ACDCRGDCFC-GG-(D)(KLAKLAK)(2) peptide (900 microM in D-PBSA, i.e. Dulbecco's PBS without Ca(2+) and Mg(2+)) and size-calibrated, passively or actively targeted liposomes based on distearoylphosphatidylcholine, cholesterol, and N-carbamoyl-methoxypolyethyleneglycol coupled to distearoylphosphatidylethanolamine (PEG-DSPE) and containing gradient-entrapped doxorubicin were used. The KB (human nasopharyngeal carcinoma) cell line overexpressing folate receptors was used in the fluorescence studies of liposomal uptake. The B16-F10 melanoma cell line was used for confirming, by flow cytometry and confocal microscopy, doxorubicin intracellular transfer as well as to induce experimental tumors in C57BL/6 mice. Animal therapy was achieved with injections of vascular-disrupting peptide, doxorubicin-loaded liposomes, or alternating combined therapy. The results (tumor growth inhibition and survival) were compared using the Mann-Whitney U test and the log-rank test. Necrosis in H&E-stained tumor sections was assessed microscopically by pathologists. Treatment of C57BL/6 mice bearing B16-F10 experimental tumors with a combination of vascular-disruptive peptide and doxorubicin-carrying pegylated liposomes (either passively targeted liposomes (PTL) or folate receptor targeted) gave better therapeutic effects when tumor development was re-challenged with a second cycle of combined therapy. Marked inhibition of tumor growth and a statistically significant extension of the lifespan of the treated mice were observed when the re-challenge involved the use of folate receptor-targeted liposomes (FTL). Anticancer therapy involving vascular-disruptive peptide and doxorubicin delivered via pegylated folate receptor-targeted liposomes is more effective than either monotherapy, especially when tumor growth is re-challenged with the therapeutic combination.

Sochanik, Aleksander
Mitrus, Iwona
Smolarczyk, Ryszard
Cicho?, Tomasz
Snietura, Miros?aw
Czaja, Maria
Szala, Stanis?aw
Item Type: 
Journal Article
Publication Title: 
Archivum Immunologiae Et Therapiae Experimentalis
Journal Abbreviation: 
Arch. Immunol. Ther. Exp. (Warsz.)
Publication Date: 
Publication Year: 
Library Catalog: 
NCBI Published Medical (?)
PMID: 20383751

Turabian/Chicago Citation

Aleksander Sochanik, Iwona Mitrus, Ryszard Smolarczyk, Tomasz Cicho?, Miros?aw Snietura, Maria Czaja and Stanis?aw Szala. 2010-06. "Experimental anticancer therapy with vascular-disruptive peptide and liposome-entrapped chemotherapeutic agent." Archivum Immunologiae Et Therapiae Experimentalis 58: 3: 235-245. 10.1007/s00005-010-0077-y.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1007/s00005-010-0077-y | issn = 1661-4917 | volume = 58 | pages = 235-245 | last = Sochanik | first = Aleksander | coauthors = Mitrus, Iwona, Smolarczyk, Ryszard, Cicho?, Tomasz, Snietura, Miros?aw, Czaja, Maria, Szala, Stanis?aw | title = Experimental anticancer therapy with vascular-disruptive peptide and liposome-entrapped chemotherapeutic agent | journal = Archivum Immunologiae Et Therapiae Experimentalis | date = 2010-06 | pmid = | pmc = }} </ref>