In vivo evaluation of CD38 and CD138 as targets for nanoparticle-based drug delivery in multiple myeloma
Open Access
- 2 November 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Hematology & Oncology
- Vol. 13 (1), 1-15
- https://doi.org/10.1186/s13045-020-00965-4
Abstract
Background Drug-loaded nanoparticles have established their benefits in the fight against multiple myeloma; however, ligand-targeted nanomedicine has yet to successfully translate to the clinic due to insufficient efficacies reported in preclinical studies. Methods In this study, liposomal nanoparticles targeting multiple myeloma via CD38 or CD138 receptors are prepared from pre-synthesized, purified constituents to ensure increased consistency over standard synthetic methods. These nanoparticles are then tested both in vitro for uptake to cancer cells and in vivo for accumulation at the tumor site and uptake to tumor cells. Finally, drug-loaded nanoparticles are tested for long-term efficacy in a month-long in vivo study by tracking tumor size and mouse health. Results The targeted nanoparticles are first optimized in vitro and show increased uptake and cytotoxicity over nontargeted nanoparticles, with CD138-targeting showing superior enhancement over CD38-targeted nanoparticles. However, biodistribution and tumor suppression studies established CD38-targeted nanoparticles to have significantly increased in vivo tumor accumulation, tumor cell uptake, and tumor suppression over both nontargeted and CD138-targeted nanoparticles due to the latter's poor selectivity. Conclusion These results both highlight a promising cancer treatment option in CD38-targeted nanoparticles and emphasize that targeting success in vitro does not necessarily translate to success in vivo.Keywords
Funding Information
- Walther Cancer Foundation (PreClinical Testing Facility Proof-of-Concept Grant, Advancing Basic Cancer (ABC) Grant)
- Kelly Cares Foundation
- National Cancer Institute (R33CA206922)
- American Cancer Society (Research Scholar Award)
This publication has 54 references indexed in Scilit:
- Folic acid-conjugated silica capped gold nanoclusters for targeted fluorescence/X-ray computed tomography imagingJournal of Nanobiotechnology, 2013
- Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomideInternational Journal of Oncology, 2012
- Rationally engineered nanoparticles target multiple myeloma cells, overcome cell-adhesion-mediated drug resistance, and show enhanced efficacy in vivoBlood Cancer Journal, 2012
- CD38 expression, function, and gene resequencing in a human lymphoblastoid cell line-based model systemLeukemia & Lymphoma, 2010
- Role of syndecan‐1 (CD138) in cell survival of human urothelial carcinomaCancer Science, 2009
- Clonogenic Multiple Myeloma Progenitors, Stem Cell Properties, and Drug ResistanceCancer Research, 2008
- Flow Cytometric Immunophenotypic Analysis of 306 Cases of Multiple MyelomaAmerican Journal of Clinical Pathology, 2004
- Flow Cytometric Immunophenotypic Analysis of 306 Cases of Multiple MyelomaAmerican Journal of Clinical Pathology, 2004
- Inhibition of Hair Follicle Growth by a Laminin-1 G-Domain Peptide, RKRLQVQLSIRT, in an Organ Culture of Isolated Vibrissa Rudiment11The authors have declared not to have a conflict of interest.Journal of Investigative Dermatology, 2002
- CD38 expression is an important prognostic marker in chronic lymphocytic leukaemiaLeukemia, 2002