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Supplementary Table 1, Figures 1 - 5 from Targeted Delivery of microRNA-29b by Transferrin-Conjugated Anionic Lipopolyplex Nanoparticles: A Novel Therapeutic Strategy in Acute Myeloid Leukemia

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posted on 2023-03-31, 17:32 authored by Xiaomeng Huang, Sebastian Schwind, Bo Yu, Ramasamy Santhanam, Hongyan Wang, Pia Hoellerbauer, Alice Mims, Rebecca Klisovic, Alison R. Walker, Kenneth K. Chan, William Blum, Danilo Perrotti, John C. Byrd, Clara D. Bloomfield, Michael A. Caligiuri, Robert J. Lee, Ramiro Garzon, Natarajan Muthusamy, Ly James Lee, Guido Marcucci

PDF file - 325K, Supplemental Table 1: Particle Size Distribution and Zeta Potential; Supplemental Figure 1: Transferrin receptor (CD71) expression on AML patient blasts; Supplemental Figure 2: miR entrapment efficiency; Supplemental Figure 3: Relative expression of miR-29b in AML cell lines, patient blasts and bone marrow samples from healthy donors; Supplemental Figure 4: Expression of pri-miR-29b-1 and pri-miR-29b-2 in AML cell lines and patient blasts following Tf-NP-miR-29b treatment; Supplemental Figure 5: Safety profile of Tf-NPs treatment in immune competent mice.

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ARTICLE ABSTRACT

Purpose:miR-29b directly or indirectly targets genes involved in acute myeloid leukemia (AML), namely, DNMTs, CDK6, SP1, KIT, and FLT3. Higher miR-29b pretreatment expression is associated with improved response to decitabine and better outcome in AML. Thus, designing a strategy to increase miR-29b levels in AML blasts may be of therapeutic value. However, free synthetic miRs are easily degraded in bio-fluids and have limited cellular uptake. To overcome these limitations, we developed a novel transferrin-conjugated nanoparticle delivery system for synthetic miR-29b (Tf-NP-miR-29b).Experimental Design: Delivery efficiency was investigated by flow cytometry, confocal microscopy, and quantitative PCR. The expression of miR-29b targets was measured by immunoblotting. The antileukemic activity of Tf-NP-miR-29b was evaluated by measuring cell proliferation and colony formation ability and in a leukemia mouse model.Results: Tf-NP-miR-29b treatment resulted in more than 200-fold increase of mature miR-29b compared with free miR-29b and was approximately twice as efficient as treatment with non-transferrin–conjugated NP-miR-29b. Tf-NP-miR-29b treatment significantly downregulated DNMTs, CDK6, SP1, KIT, and FLT3 and decreased AML cell growth by 30% to 50% and impaired colony formation by approximately 50%. Mice engrafted with AML cells and then treated with Tf-NP-miR-29b had significantly longer survival compared with Tf-NP-scramble (P = 0.015) or free miR-29b (P = 0.003). Furthermore, priming AML cell with Tf-NP-miR-29b before treatment with decitabine resulted in marked decrease in cell viability in vitro and showed improved antileukemic activity compared with decitabine alone (P = 0.001) in vivo.Conclusions: Tf-NP effectively delivered functional miR-29b, resulting in target downregulation and antileukemic activity and warrants further investigation as a novel therapeutic approach in AML. Clin Cancer Res; 19(9); 2355–67. ©2013 AACR.

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