Abstract
ErbB2 is a type of receptor tyrosine kinase, which is known to be involved in tumorigenesis, tumor aggressiveness, and clinical outcome. ErbB2-targeting therapy using therapeutic antibodies has been successful in breast cancer treatment. However, the need for repeated treatments and the high cost are major disadvantages with monoclonal antibody therapies. Compared with antibodies, peptides are cheap, relatively stable, and have low immunogenicity. We have developed a highly specific cancer-targeting drug delivery system using a targeting peptide to maximize the therapeutic efficiency of rapamycin and to help prevent drug resistance in ErbB2-positive breast cancer. Physicochemical characterization confirmed the successful construction of ErbB2-targeting liposomes (ErbB2Lipo). A comparison of a scrambled peptide (ScrErbB2) with the ErbB2-targeting peptide confirmed that these peptides had similar properties except for the targeting ability. The ErbB2Lipo exhibited higher delivery efficiency in ErbB2 positive BT-474 cells than non-targeting liposomes conjugated with ScrErbB2 (ScrErbB2Lipo). This peptide-targeting strategy has the potential to improve the efficacy of chemotherapy in ErbB2-positive cancers.
Highlights
Cancer is one of the most devastating diseases in the world with numbers of new cases increasing every year
A pre-chilled cocktail solution for deprotection at a ratio of trifluoroacetic acid (TFA)/distilled water (D.W.)/TIS = 95:2.5:2.5 was added to the column and stirred for 2 h to cleave the peptides from the resin
The ErbB2-targeting peptide and ScrErbB2 were synthesized by solid-phase peptide synthesis (SPPS), which is the most commonly used methodology for the synthesis of peptides [25]
Summary
Cancer is one of the most devastating diseases in the world with numbers of new cases increasing every year. Targeted therapy is considered an appropriate choice to kill cancer cells more efficiently than non-targeted treatments, and as a way to overcome systemic toxicity, especially in ErbB2-positive breast cancer patients undergoing conventional systemic chemotherapy, radiotherapy, or invasive surgery [5] This strategy has been extensively applied by conjugating anti-cancer drugs with various drug delivery systems and has recently been emphasized for precision medicine [6,7,8,9,10]. Several clinical trials have demonstrated that Rapa failed to completely inhibit tumor cells [20,21,22] In this case, we have developed a highly specific ErbB2-targeting drug delivery system for maximizing the therapeutic efficiency of Rapa in ErbB2-positive breast cancer. The ErbB2-targeting liposomes directly controlled the PI3K-AKT3-mTOR pathway and may be able to downregulate tumor growth
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