Novel tumor-targeted liposomes comprised of an MDM2 antagonist plus proteasome inhibitor display anti-tumor activity in a xenograft model of bortezomib-resistant Waldenstrom macroglobulinemia

Vijay Sagar Madamsetty, Aneel Paulus, Sharoon Akhtar, Alak Manna, Harikrishna Reddy Rachamalla, Raj Kumar Banerjee, Debabrata Mukhopadhyay, Asher Chanan-Khan

Research output: Contribution to journalArticle

Abstract

Targeted drug delivery remains an active area of investigation in hematologic cancers. We have previously reported on a novel nanoparticle formulation (D1X) that can encapsulate drugs within a liposome whose lipid bilayer contains dexamethasone, which serves as a targeting ligand for drug delivery to tumor cells that express glucocorticoid receptors. We tested the activity of D1X-encapsulated bortezomib (D1XB) in combination with D1X-encapsulated nutlin (D1XN) in B-lymphoma/Waldenstrom macroglobulinemia (WM) cells. WM cells treated with D1XB + D1XN experienced cell cycle arrest, ER stress and apoptosis. In mice xenografted with bortezomib-resistant WM cells, D1XB + D1XN treatment resulted in significantly lower tumor burden compared to vehicle or nonliposomal parent drugs. In vivo biodistribution studies showed minimal uptake of D1X-based drugs in normal mice tissues. Our studies demonstrate that highly targeted delivery of both bortezomib and nutlin encapsulated in D1X nanoparticles are cytotoxic to and delay in vivo growth of bortezomib-resistant WM cells.

Original languageEnglish (US)
JournalLeukemia and Lymphoma
DOIs
StateAccepted/In press - 2020

Keywords

  • bortezomib
  • nanoparticles
  • Waldenstrom macroglobulinemia

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Novel tumor-targeted liposomes comprised of an MDM2 antagonist plus proteasome inhibitor display anti-tumor activity in a xenograft model of bortezomib-resistant Waldenstrom macroglobulinemia'. Together they form a unique fingerprint.

  • Cite this