Targeting Approaches of Nanomedicines in Acute Myeloid Leukemia

Huang, Xiao Jun; Lin, Hai; Huang, Feng; Xie, Yangyang; Wong, Ka Hong; Chen, Xiaoyu; Wu, Dongyue; Lu, Aiping; Yang, Zhijun

doi:10.1177/1559325819887048

Cited by 18 publications

(14 citation statements)

References 150 publications

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“…103 Other liposomal formulations of chemotherapy drugs, such as vincristine, doxorubicin and annamycin, also demonstrate similar efficacy in modifying drugs' in vivo pharmacokinetics, as reviewed elsewhere. 104,105 3.1.2 Polymeric nanoparticles. Besides liposomes, there is a polymeric nanoparticle-based delivery system in clinical trial (NCT03217838).…”

Section: Strategies In Modifying Drug Pharmacokineticsmentioning

confidence: 99%

Delivery strategies in treatments of leukemia

Zhang

Qiao

et al. 2022

Chem. Soc. Rev.

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Section: Strategies In Modifying Drug Pharmacokineticsmentioning

confidence: 99%

Delivery strategies in treatments of leukemia

Zhang

Qiao

et al. 2022

Chem. Soc. Rev.

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“…1 Clinical outcomes of patients with AML are still poor, with <30% surviving 5 years and higher incidence and an almost 90% mortality rate for older patients (>65 years). 2,3 Current treatmentsfor AML mainly consist of standard chemotherapy (a combination of cytarabine and daunorubicin [Drn] or idarubicin), targeted therapy using FLT3 inhibitors, including midostaurin, quizartinib, and cabozantinib, and immunotherapy, eg, gemtuzumab ozogamicin (anti-CD33 monoclonal antibody conjugated with calicheamicin). [3][4][5][6] Unfortunately, current treatments still have therapeutic obstacles, including lower compliance, because of serious toxicity and therapeutic efficacy due to drug resistance.…”

Section: Introductionmentioning

confidence: 99%

“…2,3 Current treatmentsfor AML mainly consist of standard chemotherapy (a combination of cytarabine and daunorubicin [Drn] or idarubicin), targeted therapy using FLT3 inhibitors, including midostaurin, quizartinib, and cabozantinib, and immunotherapy, eg, gemtuzumab ozogamicin (anti-CD33 monoclonal antibody conjugated with calicheamicin). [3][4][5][6] Unfortunately, current treatments still have therapeutic obstacles, including lower compliance, because of serious toxicity and therapeutic efficacy due to drug resistance. Therefore, it is urgent to exploit new therapeutic strategies to improve treatment outcomes.…”

Section: Introductionmentioning

confidence: 99%

Binary Nanodrug-Delivery System Designed for Leukemia Therapy: Aptamer- and Transferrin-Codecorated Daunorubicin- and Luteolin-Coloaded Nanoparticles

Zhu¹,

Zhang²,

Chen³

2023

DDDT

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Objective This study aimed to develop a binary nanodrug-delivery system decorated with aptamers (APs) and transferrin (Tf) and loaded with daunorubicin (Drn) and luteolin (Lut) for the treatment of leukemia. Methods Oligonucleotide AP- and Tf-contaiing ligands were designed and synthesized separately. AP-decorated Drn-loaded nanoparticles (AP-Drn NPs) and Tf-Lut NPs were prepared by self-assembly. An AP- and Tf-codecorated Drn- and Lut-coloaded nanodrug-delivery system (AP/Tf-Drn/Lut NPs) was prepared by self-assembly of AP-Drn NPs and Tf-Lut NPs. In vitro and in vivo efficiency of the system was evaluated on leukemia cell line and cell-bearing mouse model in comparison with single ligand–decorated, single drug–loaded and free-drug formulations. Results AP/Tf-Drn/Lut NPs were spherical and nanosized (187.3±5.3 nm) and loaded with about 85% of drugs. In vitro cytotoxicity of AP/Tf-Drn/Lut NPs was remarkably higher than single ligand–decorated ones. Double drug–loaded AP/Tf-Drn/Lut NPs exhibited higher tumor-cell inhibition than single drug–loaded ones, which showed a synergic effect of the two drugs. AP/Tf-Drn/Lut NPs achieved the most efficient antileukemic activity and absence of toxicity in vivo. Conclusion The present study showed that AP/Tf-Drn/Lut NPs are a promising drug-delivery system for targeted treatment of leukemia, due to the synergic effect of the two drugs in this system. The limitations of this system include stability during large-scale production and application from bench to bedside.

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“…Cytarabine-loaded liposomes have been explored for the treatment of AML. To overcome the stability and batch variation issues, polymeric carriers like PLGA and PCL have been used for delivering chemotherapeutic agents for AML therapy . These polymers, however, degrade into acid byproducts, which could elicit inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

“…To overcome the stability and batch variation issues, polymeric carriers like PLGA and PCL have been used for delivering chemotherapeutic agents for AML therapy. 29 These polymers, however, degrade into acid byproducts, which could elicit inflammatory response. Hence, pH-sensitive polymers such as PCADK that do not form acidic byproducts could be explored for delivery of chemotherapeutic agents into AML cells to achieve efficient delivery as well as lower inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Anticancer Activity of pH-Sensitive Polyketal Nanoparticles for Acute Myeloid Leukemia

2021

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Polyketals are a class of acid-responsive polymers that have been relatively less explored for drug delivery applications compared to polyesters. The degradation of these polymers is accelerated in an acidic medium and does not result in acidic byproducts. Their biocompatibility depends on the diol used for the synthesis. The present work aims to synthesize, characterize, and fabricate nanospheres of an aliphatic polyketal for delivery of the nucleotide analogue cytarabine toward the treatment of acute myeloid leukemia (AML). The internalization mechanism of the nanospheres was probed, and its implication on the nuclear localization and escape from the endo-lysosomal compartments were studied. The drug-loaded polyketal nanoparticles reduced the cell viability to a greater extent compared with the free drug. The effect of the drug-loaded polyketal nanoparticles on the differential gene expression of leukemic cells was investigated for the first time to understand their therapeutic implications. It was found that treatment with drug-loaded polyketal nanoparticles downregulated AML-specific genes involved in cell proliferation and recurrence compared to the free drug. The protein expression studies were performed for selected genes obtained from gene expression analysis. Biodistribution studies showed that the poly(cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK) nanoparticles exhibit prolonged circulation time. Overall, our results suggest that polyketal-based delivery of cytarabine represents a more effective alternative strategy for AML therapy.

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Targeting Approaches of Nanomedicines in Acute Myeloid Leukemia

Cited by 18 publications

References 150 publications

Delivery strategies in treatments of leukemia

Delivery strategies in treatments of leukemia

Binary Nanodrug-Delivery System Designed for Leukemia Therapy: Aptamer- and Transferrin-Codecorated Daunorubicin- and Luteolin-Coloaded Nanoparticles

Evaluation of the Anticancer Activity of pH-Sensitive Polyketal Nanoparticles for Acute Myeloid Leukemia

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