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Tumor microenvironment-targeted nanoparticles loaded with bortezomib and ROCK inhibitor improve efficacy in multiple myeloma
Tumor microenvironment-targeted nanoparticles loaded with bortezomib and ROCK inhibitor improve efficacy in multiple myeloma
- Source :
- Nature Communications, Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020)
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
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.<br />The tumour microenvironment (TME) has a major role in chemoresistance in multiple myeloma. The authors show that a nanoparticle targeted to TME and loaded with bortezomib (BTZ) and Y27632 is more effective than free drugs, non-targeted and single-agent controls and reduces BTZ-related side effects.
- Subjects :
- 0301 basic medicine
Pyridines
medicine.medical_treatment
General Physics and Astronomy
Myeloma
Apoptosis
Drug resistance
Bortezomib
Mice
0302 clinical medicine
Cell Movement
hemic and lymphatic diseases
Tumor Microenvironment
Multiple myeloma
rho-Associated Kinases
Liposome
Membrane Glycoproteins
Multidisciplinary
Tumor Burden
P-Selectin
src-Family Kinases
medicine.anatomical_structure
030220 oncology & carcinogenesis
Drug delivery
Disease Progression
Multiple Myeloma
Protein Binding
Signal Transduction
medicine.drug
Cancer microenvironment
Cell Survival
Science
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Cell Line, Tumor
Cell Adhesion
Human Umbilical Vein Endothelial Cells
medicine
Animals
Humans
Protein Kinase Inhibitors
Cell Proliferation
Tumor microenvironment
Chemotherapy
business.industry
General Chemistry
medicine.disease
Amides
030104 developmental biology
Focal Adhesion Protein-Tyrosine Kinases
Liposomes
Cancer research
Nanoparticles
sense organs
Bone marrow
business
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....e14060bd7bccf7eab65002ce7a781919
- Full Text :
- https://doi.org/10.1038/s41467-020-19932-1