Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent

被引：52

作者：

Accardo, Antonella ^{[1
,2
,4
]}

Salsano, Giuseppina ^{[3
]}

Morisco, Anna ^{[5
]}

Aurilio, Michela ^{[5
]}

Parisi, Antonio ^{[6
]}

Maione, Francesco ^{[6
]}

Cicala, Carla ^{[6
]}

Tesauro, Diego ^{[1
,2
,4
]}

Aloj, Luigi ^{[5
]}

De Rosa, Giuseppe ^{[3
]}

Morelli, Giancarlo ^{[1
,2
,4
]}

机构：

[1] Univ Naples Federico II, CIRPeB, Dept Biol Sci, I-80134 Naples, Italy

[2] Univ Naples Federico II, IBB CNR, I-80134 Naples, Italy

[3] Univ Naples Federico II, Dept Pharmaceut Chem, I-80134 Naples, Italy

[4] Invectors Srl, Naples, Italy

[5] Fdn G Pascale, Ist Nazl Studio & Cura Tumori, Dept Nucl Med, Naples, Italy

[6] Univ Naples Federico II, Dept Expt Pharmacol, I-80134 Naples, Italy

来源：

INTERNATIONAL JOURNAL OF NANOMEDICINE | 2012年 / 7卷

关键词：

bombesin peptide; doxorubicin delivery; gastrin-releasing peptide receptors; PC-3; cells; theranostic applications; HUMAN PROSTATE; GADOLINIUM COMPLEXES; BLOOD-VESSELS; IN-VIVO; TUMOR; DOXORUBICIN; NANOPARTICLES; ACCUMULATION; EXPRESSION; PROTEINS;

D O I：

10.2147/IJN.S29242

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

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 degrees C), compared with peptide-free DSPC liposomes (1.4% +/- 0.2% at 37 degrees 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.

引用

页码：2007 / 2017

页数：11

共 41 条

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