Green formulation and chemical characterization of Lens culinaris seed aqueous extract conjugated gold nanoparticles for the treatment of acute myeloid leukemia in comparison to mitoxantrone in a leukemic mouse model

Abstract

The high prevalence of cancer has been increased the rate of studying about the new formulation of chemotherapeutic drugs. In this regards, one of the suitable options is the use of metal nanoparticles for formulating these drugs. In the recent study, Lens culinaris seed aqueous extract conjugated gold nanoparticles (AuNPs) are reported for the first time to exert a dietary therapeutic potential compared to mitoxantrone in an animal model of acute myeloid leukemia. The synthesized AuNPs were characterized using different techniques including UV–Vis., FT‐IR, XRD, FE‐SEM, and TEM. DPPH free radical scavenging test was done to evaluate the antioxidant potentials of HAuCl4, L. culinaris, AuNPs, and mitoxantrone. For the analyzing of cytotoxicity effects of HAuCl4, L. culinaris, AuNPs, and mitoxantrone, MTT assay was used on HUVEC, 32D‐FLT3‐ITD, Human HL‐60/vcr, and Murine C1498 cell lines. In vivo assay, induction of acute myeloid leukemia was done by 7,12‐Dimethylbenz[a]anthracene (DMBA) in 75 mice. Then, the animals were randomly divided into six subgroups, including control, untreated, HAuCl4, L. culinaris, AuNPs, and mitoxantrone. SEM and TEM images showed uniform spherical morphology and average diameters of 10–40 nm for the nanoparticles. DPPH test revealed similar antioxidant potentials for mitoxantrone and AuNPs. Similar to mitoxantrone, AuNPs had low cell viability dose‐dependently against 32D‐FLT3‐ITD, Human HL‐60/vcr, and Murine C1498 cell lines without any cytotoxicity on HUVEC cell line. AuNPs and mitoxantrone significantly (p ≤ 0.05) reduced the weight and volume of liver and spleen, the pro‐inflammatory cytokines, and the total WBC, blast, neutrophil, monocyte, eosinophil, and basophil counts and increased the mRNA expression of Sphingosine‐1‐phosphate receptor‐1 and Sphingosine‐1‐phosphate receptor‐5, the anti‐inflammatory cytokines, and the lymphocyte, platelet, and RBC parameters as compared to the untreated mice. It looks that AuNPs can be administrated as a chemotherapeutic supplement or drug for the treatment of acute myeloid leukemia in the clinical trial.

Antineoplastic activity of biogenic silver and gold nanoparticles to combat leukemia: Beginning a new era in cancer theragnostic

“…These results revealed that these biosynthesized AuNPs could be either used in combination with chemotherapeutic drugs or even instead of them ( Fig. 9 ) [114] .…”

“… Biological source Size (nm) In vitro cell lines Dose IC50 value Ref. Hibiscus sabdariffa 15–45 C1498 HL‐60/vcr 32D‐FLT3‐ITD 0–1000 µg/ml 185 µg/mL 189 µg/mL 309 µg/mL [118] Camellia sinensis 20–30 C1498 HL‐60/vcr 32D‐FLT3‐ITD 0–1000 µg/ml 158 µg/mL 224 µg/mL 258 µg/mL [119] Boswellia serrata 15–30 C1498 HL‐60/vcr 32D‐FLT3‐ITD 0–1000 µg/ml 219 µg/mL 329 µg/mL 320 µg/mL [120] Lens culinaris 10–40 C1498 HL‐60/vcr 32D‐FLT3‐ITD 0–1000 µg/ml 212 µg/mL 246 µg/mL 367 µg/mL [121] Thymus vulgaris 10–30 C1498 HL‐60/vcr 32D‐FLT3‐ITD 0–1000 µg/ml 186 µg/mL 218 µg/mL 336 µg/mL [122] Cannabis sativa 18.6 MOLT-3 TALL-104 J .RT3 -T3.5 0–1000 µg/ml 329 µg/mL 381 µg/mL 502 µg/mL [123] Verbena officinalis 35 Jurkat 0.1–100 µmol 1,08 µmol (24 h) 0.65 µmol (48 h) 0.39 µmol (72 h) [124] Thymus vulgaris 10–30 Murine C1498 Human HL‐60/vcr 32D‐FLT3‐ITD 1–1000 µg/mL 186 µg/mL 218 µg/mL 336 µg/mL [122] Boswellia serrata 15–30 Murine C1498 Human HL‐60/vcr 32D‐FLT3‐ITD 1–1000 µg/mL 219 µg/mL 329 µg/mL 320 µg/mL [125] Abelmoschus esculentus L. 4–32 Jurkat K-562 1–50 µg/mL 8.17 µg/mL ∼50 µg/mL [126] Draco...…”

“…(D) In vivo results of anticancer activity of AuNPs, a) The leukemic blasts infiltrating in histological stain of the spleen, and b) Leukocytosis in the smear of peripheral blood. Reprinted from [114] with permission from Wiley. …”

Theranostic Potentials of Gold Nanomaterials in Hematological Malignancies

“…Biogenic AuNPs (b-AuNPs) synthesized from Boswellia serrata or Lens culinaris displayed cytotoxicity toward Human HL-60/vcr, Murine C1498, and 32D-FLT3-ITD cells, which was comparable to the mitoxantrone. However, b-AuNPs were less cytotoxic toward HUVEC cells compared to mitoxantrone [157,158]. In a 7,12-dimethylbenz[a]anthraceneinduced AML mice model, b-AuNPs (1 mg/kg body weight) such as mitoxantrone significantly increased lymphocyte, platelet, RBC parameters, and anti-inflammatory cytokines level (IFNα, IL4, IL5, IL10, and IL13), while decreasing the level of pro-inflammatory cytokines (TNFα, IFNY, IL1, IL6, IL12, and IL18) compared to untreated mice [157,158].…”

“…In a 7,12-dimethylbenz[a]anthraceneinduced AML mice model, b-AuNPs (1 mg/kg body weight) such as mitoxantrone significantly increased lymphocyte, platelet, RBC parameters, and anti-inflammatory cytokines level (IFNα, IL4, IL5, IL10, and IL13), while decreasing the level of pro-inflammatory cytokines (TNFα, IFNY, IL1, IL6, IL12, and IL18) compared to untreated mice [157,158]. Furthermore, b-AuNPs and mitoxantrone significantly increased the expression of sphingosine-1-phosphate receptor-1 and sphingosine-1-phosphate receptor-5 mRNA compared to the control mice [157,158]. Ahmeda et al (2020) [157,158]…”