Journal
MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
Volume 119, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.msec.2020.111583
Keywords
Acute myeloid leukemia; Folate receptor up-regulation; Biomimetic albumin nanoparticles; All-trans retinoic acid; siRNA
Categories
Funding
- National Natural Science Foundation of China [81773183, 81571788]
- Postgraduate Research and Practice Innovation of Jiangsu Province [KYCX19_1973]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Institute of Hematopoietic Stem Cell Transplantation in Soochow University
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Acute myeloid leukemia is a common and fatal hematological malignancy with poor outcomes, and utilizing folate receptor beta for nanoparticle modification shows promise in improving targeted therapy. Upregulating FR beta expression through all-trans retinoic acid enhances the active tumor-targeting effect of FA-modified nanoparticles in AML treatment.
Acute myeloid leukemia (AML) is the most universal type and fatal disease of hematological malignancy, with poor outcomes despite chemotherapy and bone marrow transplantations. Benefited from the narrow tissue specificity of folate receptor beta (FR beta) aberrantly expressed on hematological linage cell lines, NPs modified with folate acid (FA) has been widely applied for crossing cell membrane barriers in FR-targeted therapies for AML. Thus, the biomimetic nanoparticles (NPs) mediated by FR beta were conducted by an albumin modifier as previously synthesized and cationic liposomes. However, how to further enhance the tumor-targeting and cellular uptake of NPs have been great challenges in cancer therapy. It was reported that FR beta could be selectively augmented by all-trans retinoic acid (ATRA). Herein, we demonstrated the enhanced active tumor-targeting of FA-modified siRNA-loaded biomimetic albumin NPs (Lip-S@FBH) could be achieved by upregulating FR beta expression via ATRA NPs. And the systematic administration of ATRA NPs significantly promoted endocytosis and thereby increased the intracellular concentration of Lip-S@FBH. This strategy combined the FR beta amplification effect with the effective delivery of siRNA, is mostly desirable for the AML-targeting therapy.
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