ArticleBlood cancer journal2012
Rationally engineered nanoparticles target multiple myeloma cells, overcome cell-adhesion-mediated drug resistance, and show enhanced efficacy in vivo.
Article in Blood cancer journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- Extracellular vesicles: powerful candidates in nano-drug delivery systems.Drug delivery and translational research · 2024Pooled it
- Cellular adhesion-dependent 3D morphogenesis indicating brain tumor aggressiveness and chemosensitivity in spherical cavity culture.Experimental hematology & oncology · 2026Article
- Investigating the functions and molecular mechanisms of DTX3L in cancer progression.Frontiers in oncology · 2026Review
- Multiple myeloma inhibitory effects of natural compounds: enhancement through nanoparticle carriers.Frontiers in pharmacology · 2025Review
- Recent advances in targeted drug delivery systems for multiple myeloma.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
- Current advance of nanotechnology in diagnosis and treatment for malignant tumors.Signal transduction and targeted therapy · 2024Review
- Review
- Increased Bone Marrow Uptake and Accumulation of Very-Late Antigen-4 Targeted Lipid Nanoparticles.Pharmaceutics · 2023Article
- Delivery of Theranostic Nanoparticles to Various Cancers by Means of Integrin-Binding Peptides.International journal of molecular sciences · 2022Review
- Critical parameters for design and development of multivalent nanoconstructs: recent trends.Drug delivery and translational research · 2022Review
- Affinity monolith chromatography: A review of general principles and recent developments.Electrophoresis · 2021Review
- VLA4-Targeted Nanoparticles Hijack Cell Adhesion-Mediated Drug Resistance to Target Refractory Myeloma Cells and Prolong Survival.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- In vivo evaluation of CD38 and CD138 as targets for nanoparticle-based drug delivery in multiple myeloma.Journal of hematology & oncology · 2020Article
- Engineering peptide-targeted liposomal nanoparticles optimized for improved selectivity for HER2-positive breast cancer cells to achieve enhanced in vivo efficacy.Journal of controlled release : official journal of the Controlled Release Society · 2020Article
- Inhibition of Multiple Myeloma Using 5-Aza-2'-Deoxycytidine and Bortezomib-Loaded Self-Assembling Nanoparticles.Cancer management and research · 2020Article
- A Comprehensive Biological and Clinical Perspective Can Drive a Patient-Tailored Approach to Multiple Myeloma: Bridging the Gaps between the Plasma Cell and the Neoplastic Niche.Journal of oncology · 2020Review
- Targeted Approaches to Inhibit Sialylation of Multiple Myeloma in the Bone Marrow Microenvironment.Frontiers in bioengineering and biotechnology · 2019Review
- Nanotherapeutics for multiple myeloma.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2018Review
- Germline Lysine-Specific Demethylase 1 (Cancer research · 2018Article
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the continuing search for effective cancer treatments, we report the rational engineering of a multifunctional nanoparticle that combines traditional chemotherapy with cell targeting and anti-adhesion functionalities. Very late antigen-4 (VLA-4) mediated adhesion of multiple myeloma (MM) cells to bone marrow stroma confers MM cells with cell-adhesion-mediated drug resistance (CAM-DR). In our design, we used micellar nanoparticles as dynamic self-assembling scaffolds to present VLA-4-antagonist peptides and doxorubicin (Dox) conjugates, simultaneously, to selectively target MM cells and to overcome CAM-DR. Dox was conjugated to the nanoparticles through an acid-sensitive hydrazone bond. VLA-4-antagonist peptides were conjugated via a multifaceted synthetic procedure for generating precisely controlled number of targeting functionalities. The nanoparticles were efficiently internalized by MM cells and induced cytotoxicity. Mechanistic studies revealed that nanoparticles induced DNA double-strand breaks and apoptosis in MM cells. Importantly, multifunctional nanoparticles overcame CAM-DR, and were more efficacious than Dox when MM cells were cultured on fibronectin-coated plates. Finally, in a MM xenograft model, nanoparticles preferentially homed to MM tumors with ∼10 fold more drug accumulation and demonstrated dramatic tumor growth inhibition with a reduced overall systemic toxicity. Altogether, we demonstrate the disease driven engineering of a nanoparticle-based drug delivery system, enabling the model of an integrative approach in the treatment of MM.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.