Rituxan nanoconjugation prolongs drug/cell interaction and enables simultaneous depletion and enhanced Raman detection of lymphoma cells

Abstract

Antibody therapy is a type of immunotherapy that uses monoclonal antibodies (mAbs) to specifically bind to target cells to fight cancer. These mAbs have been conjugated with a number of nanocarriers to realize the targeted delivery of chemotherapeutics. Previous data indicate that the conjugation of a mAb to a nanocarrier promoted the faster internalization (endocytosis) of the nanoconjugates. In this study, we report that the crosslinking of Rituxan, an anti-lymphoma mAb, with silver nanoparticles prevented Rituxan from entering cells and prolonged drug/cell interaction. This finding was confirmed by both imaging flow cytometric and laser scanning confocal microscopic analyses of the fluorescently labeled nanoconjugates and cells. Furthermore, nanoconjugated Rituxan resulted in the enhanced capping of CD20 molecules on the cell membrane. We were able to show that the prolonged drug/cell interaction and enhanced capping directly contributed towards improved therapeutic efficiency. This represents a significant finding indicating that the nanocarrier served not only as a simple platform for targeted delivery, but also markedly altered the antibody performance at the molecular level and mediated key biological functions. The nanoconjugates also served as a Raman probe to specifically detect single live lymphoma cells with high sensitivity via surface-enhanced Raman scattering (SERS). Via integrating the single-cell level detection sensitivity of SERS with targeted and enhanced depletion ability, this nanoconjugate can be applied as a promising tool in lymphoma theranostics.