CD33-Targeted Lipid Nanoparticles (aCD33LNs) for Therapeutic Delivery of GTI-2040 to Acute Myelogenous Leukemia

Li, Hong; Xu, Songlin; Quan, Ji-Shan; Yung, Bryant C.; Pang, Jiuxia; Zhou, Chenguang; Cho, Young Ah; Zhang, Mengzi; Liu, Shujun; Muthusamy, Natarajan; Chan, Kenneth K.; Byrd, John C.; Lee, L. James; Marcucci, Guido; Lee, Robert J.

doi:10.1021/mp5008212

Cited by 27 publications

(19 citation statements)

References 23 publications

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“…Furthermore, PLGA-antiCD44-PTL nanoparticles inhibited the Kasumi-1 leukemic cells by decreasing its viability by 40% [ 47 ]. In addition, Li et al [ 48 ] reported that CD33-targeted lipid nanoparticles (aCD33LNs) they synthesized effectively delivered GTI-2040 to the intended target to inhibit the proliferation of Kasumi-1 cells. The effect of the nanoparticles (aCD33LN/GTI-2040) was 15-fold more effective than the known antileukemic drug, Ara-C.…”

Section: Resultsmentioning

confidence: 99%

Boswellia dalzielii-Mediated Silver Nanoparticles Inhibited Acute Myeloid Leukemia (AML) Kasumi-1 Cells by Inducing Cell Cycle Arrest

Adebayo

Usman

Shittu

et al. 2020

Bioinorganic Chemistry and Applications

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Background. Acute myeloid leukemia (AML) persists to be a major health problem especially among children as effective chemotherapy to combat the disease is yet to be available. Boswellia dalzielii is a well-known herb that is traditionally used for treatment and management of many diseases including degenerative diseases. In this study, silver nanoparticles were synthesized from the phytochemicals of B. dalzielii stem bark aqueous extract. The silver nanoparticles were characterized by carrying out Fourier Transform Infrared (FTIR) spectroscopy, Energy Filtered Scanning Electron Microscopy (FESEM), X-ray diffraction, and Dynamic Light Scattering (DLS) analyses. Antioxidant capacity of the nanoparticles was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and the antiproliferative effect of the nanoparticles on Kasumi-1 leukemia cells was investigated using PrestoBlue assay. Flow cytometry analysis was performed to observe the effect of the nanoparticles on the leukemia cell cycle progression. Results. Our findings revealed that the synthesized silver nanoparticles were formed from electrons of the plant phytochemicals which include aromatic compounds, ethers, and alkynes. FESEM analysis revealed that the sizes of the nanoparticles range from 12 nm to 101 nm; however, DLS analysis estimated a larger average size of the nanoparticles (108.3 nm) because it measured the hydrodynamic radii of the nanoparticles. The zeta potential of the nanoparticles was −16 nm, and the XRD pattern of the nanoparticles has distinct peaks at 38.02°, 42.94°, 64.45°, 77.20°, and 81.47°, which is typical of face-centered cubic (fcc) structure of silver. The Trolox Equivalence Antioxidant Capacity (TEAC) of the nanoparticles was estimated to be 300.91 μM Trolox/mg silver nanoparticles. The nanoparticles inhibited Kasumi-1 cell proliferation. The half minimal inhibitory concentrations (IC50s) that inhibited Kasumi-1 cell proliferation are 49.5 μg/ml and 13.25 μg/ml at 48 and 72 hours, respectively. The nanoparticles induced cell cycle arrest in the Kasumi-1 cells at S (5% increase) and G2/M (3% increase) phases. Conclusion. The nanoparticles synthesized from the stem bark extract of B. dalzielii inhibit the growth of Kasumi-1 leukemia cells by activating cell cycle arrest; thus, they are potential antileukemic agents.

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Section: Resultsmentioning

confidence: 99%

Boswellia dalzielii-Mediated Silver Nanoparticles Inhibited Acute Myeloid Leukemia (AML) Kasumi-1 Cells by Inducing Cell Cycle Arrest

Adebayo

Usman

Shittu

et al. 2020

Bioinorganic Chemistry and Applications

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“…Liposomes were also developed to encapsulate GTI-2040 (also known as LOR-2040) and to target ribonucleotide reductase, which is overexpressed in cytarabine-resistant AML cells [71]. GTI-2040, targeting the R2 ribonucleotide reductase subunit, was evaluated in a Phase 1 clinical trial in combination with cytarabine.…”

Section: Liposomesmentioning

confidence: 99%

“…R2 downregulation was observed but no complete remission was noted, indicating that the effect of GTI-2040 needed to be enhanced [72]. GTI-2040-loaded immunoliposomes, grafted with an anti-CD33 to target AML cells, were designed and evaluated by Li et al [71]. These liposomes were previously formulated using an emulsion comprising lipids (2,3-dioleyloxy-propyltrimethylammonium chloride, dioleoylphosphatidylethanolamine, α-tocopheryl PEG-1000 succinate, and cholesterol) solubilized in ethanol and then injected in an HEPES buffer.…”

Section: Liposomesmentioning

confidence: 99%

Advances in treatment formulations for acute myeloid leukemia

Briot

Roger

Thépot

et al. 2018

Drug Discovery Today

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Acute myeloid leukemia (AML) is the most common cause of leukemia-related mortality. The combination of cytarabine and anthracycline has been the gold standard of treatment over the past 40 years, but the distribution of the drugs in the body leads to severe adverse effects. Poor prognosis of older patients with AML is the consequence not only of comorbidities, but also of chemoresistance resulting from frequent secondary AML. Numerous strategies using nanotechnologies are in development to improve drug targeting, pharmacokinetics, administration route, chemoresistance, and adverse effects generally observed. Among the four new drugs approved for AML by the US Food and Drug Administration (FDA) in 2017, Vyxeos is a novel liposomal formulation of historical AML drugs. Here, we review current AML treatments and discuss how the development of new formulations will change the therapeutic armamentarium.

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“…Additionally, study conducted on mice model presented that nanoparticles-mediated delivery of ataxia-telangiectasia-mutated ( ATM ; radiosensitization gene) ASOs provide a way to sensitize of head and neck squamous-cell carcinoma cells to irradiation [ 87 ]. The newest studies presented by Li et al confirmed great potential of these agents in the treatment of acute myelogenous leukemia [ 88 ]. However, a better understanding of uptake mechanism of ASOs is crucial for development of anti-RNAs as effective antineoplatic compounds.…”

Section: Employment Of Nanomaterials For Delivery Of Nucleic Acid-basmentioning

confidence: 99%

Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy

et al. 2016

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The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti-cancer agents. However, the physicochemical and biological diversity of nanomaterials and a broad spectrum of unique features influencing their biological action requires continuous research to assess their activity. Among numerous nanosystems designed to eradicate cancer cells, only a limited number of them entered the clinical trials. It is anticipated that progress in development of nanotechnology-based anti-cancer materials will provide modern, individualized anti-cancer therapies assuring decrease in morbidity and mortality from cancer diseases. In this review we discussed the implication of nanomaterials in design of new drugs for effective antineoplastic therapy and describe a variety of mechanisms and challenges for selective tumor targeting. We emphasized the recent advantages in the field of nanotechnology-based strategies to fight cancer and discussed their part in effective anti-cancer therapy and successful drug delivery.

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CD33-Targeted Lipid Nanoparticles (aCD33LNs) for Therapeutic Delivery of GTI-2040 to Acute Myelogenous Leukemia

Cited by 27 publications

References 23 publications

Boswellia dalzielii-Mediated Silver Nanoparticles Inhibited Acute Myeloid Leukemia (AML) Kasumi-1 Cells by Inducing Cell Cycle Arrest

Boswellia dalzielii-Mediated Silver Nanoparticles Inhibited Acute Myeloid Leukemia (AML) Kasumi-1 Cells by Inducing Cell Cycle Arrest

Advances in treatment formulations for acute myeloid leukemia

Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy

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