VIP receptors as molecular targets of breast cancer: implications for targeted imaging and drug delivery

Receptors for vasoactive intestinal peptide (VIP-R) are overexpressed in hu man breast cancer. This phenomenon may have important diagnostic and therap eutic implications because carrier systems loaded with imaging or therapeut ic agents, and with surface ligands to VIP-R could potentially be actively targeted to breast cancer. Previously, we have prepared sterically stabiliz ed liposomes (SSL) with VIP non-covalently associated on their surface. How ever, these liposomes were not able to actively target to breast cancer in rats in situ, most probably due to dissociation of non-covalently associate d VIP from SSL. Hence, there is a need to conjugate VIP covalently to SSL. This study aims to begin to address this issue and to test the targeting ab ility of VIP-SSL to n-methyl nitrosourea (MNU)-induced rat breast cancer in vitro. First, VIP was conjugated to DSPE-PEG(3400) -NHS [1,2-dioleoyl-sn-g lycero-3-phosphoethanolamine-n-[poly(ethylene glycol)]-N-hydroxy succinamid e, PEG M-w 3400] under mild conditions to obtain a predominantly 1:1 conjug ate of VIP and DSPE-PEG(3400) (DSPE-PEG(3400)-VIP), as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Next., DSPE- PEG(3400)-VIP was inserted into preformed fluorescent cholesterol (BODIPY-C hol) labeled SSL by incubation at 37 degreesC. To test breast cancer target ing ability in vitro, these VIP-SSL were subsequently incubated with MNU-in duced rat breast cancer tissue sections. The results showed that when compa red to fluorescent SSL without VIP or non-covalently attached VIP, signific antly more VIP-SSL were attached to rat breast cancer tissues indicating th at SSL with covalently attached VIP can be actively targeted to rat breast cancer tissues. This targeted carrier system is currently being explored fo r functional imaging and targeted chemotherapy of breast cancer. (C) 2001 E lsevier Science BY. All rights reserved.