@article{003d233c50a341c1a709dac47e83003f,
title = "Tumor microenvironment-targeted nanoparticles loaded with bortezomib and ROCK inhibitor improve efficacy in multiple myeloma",
abstract = "Drug resistance and dose-limiting toxicities are significant barriers for treatment of multiple myeloma (MM). Bone marrow microenvironment (BMME) plays a major role in drug resistance in MM. Drug delivery with targeted nanoparticles have been shown to improve specificity and efficacy and reduce toxicity. We aim to improve treatments for MM by (1) using nanoparticle delivery to enhance efficacy and reduce toxicity; (2) targeting the tumor-associated endothelium for specific delivery of the cargo to the tumor area, and (3) synchronizing the delivery of chemotherapy (bortezomib; BTZ) and BMME-disrupting agents (ROCK inhibitor) to overcome BMME-induced drug resistance. We find that targeting the BMME with P-selectin glycoprotein ligand-1 (PSGL-1)-targeted BTZ and ROCK inhibitor-loaded liposomes is more effective than free drugs, non-targeted liposomes, and single-agent controls and reduces severe BTZ-associated side effects. These results support the use of PSGL-1-targeted multi-drug and even non-targeted liposomal BTZ formulations for the enhancement of patient outcome in MM.",
author = "Cinzia Federico and Kinan Alhallak and Jennifer Sun and Kathleen Duncan and Feda Azab and Sudlow, {Gail P.} and {de la Puente}, Pilar and Barbara Muz and Vaishali Kapoor and Luna Zhang and Fangzheng Yuan and Matea Markovic and Joseph Kotsybar and Katherine Wasden and Nicole Guenthner and Shannon Gurley and Justin King and Daniel Kohnen and Salama, {Noha N.} and Dinesh Thotala and Hallahan, {Dennis E.} and Ravi Vij and DiPersio, {John F.} and Samuel Achilefu and Azab, {Abdel Kareem}",
note = "Funding Information: This study was supported by the Paula C. and Rodger O. Riney Blood Cancer Research Initiative Fund and National Institutes of Health (NIH) grants U54CA199092, UL1TR002345, P50CA094056, P30CA091842, and P30AR074992. K.A. was funded by an award from the National Center for Advancing Translational Sciences (NCATS) of the NIH (TL1TR002344). We acknowledge assistance with cryoTEM sample preparation and imaging from Michael Rau and James Fitzpatrick from the Washington University Center for Cellular Imaging which is supported in part by Washington University School of Medicine, the Children{\textquoteright}s Discovery Institute of Washington University, St. Louis Children{\textquoteright}s Hospital (CDI-CORE-2015-505 and CDI-CORE-2019-813), and the Foundation for Barnes-Jewish Hospital (3770). We also acknowledge Crystal Idleburg from the Washington University Muscoskeletal Research Center for helping processing slides for immunofluorescence. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
doi = "10.1038/s41467-020-19932-1",
language = "English",
volume = "11",
journal = "Nature communications",
issn = "2041-1723",
number = "1",
}