Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent.
De Rosa, Giuseppe
Int J Nanomedicine
Informa UK Limited
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Accardo, A., Salsano, G., Morisco, A., Aurilio, M., Parisi, A., Maione, F., Cicala, C., et al. (2012). Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent.. Int J Nanomedicine, 7 2007-2017. https://doi.org/10.2147/IJN.S29242
OBJECTIVES: Drug delivery systems consisting of liposomes displaying a cell surface receptor-targeting peptide are being developed to specifically deliver chemotherapeutic drugs to tumors overexpressing a target receptor. This study addresses novel liposome composition approaches to specifically target tissues overexpressing bombesin (BN) receptors. METHODS: A new amphiphilic peptide derivative (MonY-BN) containing the BN(7-14) peptide, the DTPA (diethylenetriaminepentaacetate) chelating agent, a hydrophobic moiety with two C(18) alkyl chains, and polyethylene glycol spacers, has been synthesized by solid-phase methods. Liposomes have been generated by co-aggregation of MonY-BN with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). The structural and biological properties of these new target-selective drug-delivery systems have been characterized. RESULTS: Liposomes with a DSPC/MonY-BN (97/3 molar ratio) composition showed a diameter of 145.5 ± 31.5 nm and a polydispersity index of 0.20 ± 0.05. High doxorubicin (Dox) loading was obtained with the remote pH gradient method using citrate as the inner buffer. Specific binding to PC-3 cells of DSPC/MonY-BN liposomes was obtained (2.7% ± 0.3%, at 37°C), compared with peptide-free DSPC liposomes (1.4% ± 0.2% at 37°C). Incubation of cells with DSPC/ MonY-BN/Dox showed significantly lower cell survival compared with DSPC/Dox-treated cells, in the presence of 100 ng/mL and 300 ng/mL drug amounts, in cytotoxicity experiments. Intravenous treatment of PC-3 xenograft-bearing mice with DSPC/MonY-BN/Dox at 10 mg/kg Dox dose produced higher tumour growth inhibition (60%) compared with nonspecific DSPC/ Dox liposomes (36%) relative to control animals. CONCLUSION: The structural and loading properties of DSPC/MonY-BN liposomes along with the observed in-vitro and in-vivo activity are encouraging for further development of this approach for target-specific cancer chemotherapy.
Cell Line, Tumor, Animals, Mice, Inbred BALB C, Humans, Mice, Mice, Nude, Prostatic Neoplasms, Pentetic Acid, Doxorubicin, Bombesin, Phosphatidylcholines, Peptide Fragments, Receptors, Bombesin, Antineoplastic Agents, Liposomes, Drug Carriers, Surface-Active Agents, Drug Delivery Systems, Xenograft Model Antitumor Assays, Female, Male, Nanomedicine
External DOI: https://doi.org/10.2147/IJN.S29242
This record's URL: https://www.repository.cam.ac.uk/handle/1810/287418
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