Bioorthogonal two-component drug delivery in HER2(+) breast cancer mouse models

Research output: Contribution to journalArticle

Abstract

The HER2 receptor is overexpressed in approximately 20% of breast cancers and is associated with tumorigenesis, metastasis, and a poor prognosis. Trastuzumab is a first-line targeted drug used against HER2(+) breast cancers; however, at least 50% of HER2(+) tumors develop resistance to trastuzumab. To treat these patients, trastuzumab-based antibody-drug conjugates (ACDs) have been developed and are currently used in the clinic. Despite their high efficacy, the long circulation half-life and non-specific binding of cytotoxic ADCs can result in systemic toxicity. In addition, standard ADCs do not provide an image-guided mode of administration. Here, we have developed a two-component, two-step, pre-targeting drug delivery system integrated with image guidance to circumvent these issues. In this strategy, HER2 receptors are pre-labeled with a functionalized trastuzumab antibody followed by the delivery of drug-loaded nanocarriers. Both components are cross-linked by multiple bioorthogonal click reactions in situ on the surface of the target cell and internalized as nanoclusters. We have explored the efficacy of this delivery strategy in HER2(+) human breast cancer models. Our therapeutic study confirms the high therapeutic efficacy of the new delivery system, with no significant toxicity.

Original languageEnglish (US)
Article number24298
JournalScientific Reports
Volume6
DOIs
StatePublished - Apr 12 2016

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Bioorthogonal two-component drug delivery in HER2(+) breast cancer mouse models'. Together they form a unique fingerprint.

  • Cite this