Evidence map›Paper›PMID 38685808›Full record

ArticleAnti-cancer agents in medicinal chemistry2024

Improving Tamoxifen Performance in Inducing Apoptosis and Hepatoprotection by Loading on a Dual Nanomagnetic Targeting System.

Yanfang Zhao, Wanbao Ding, Peixian Zhang, Lei Deng, Yi Long, Jiuqin Lu, Fereshteh Shiri, Mostafa Heidari Majd

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Article in Anti-cancer agents in medicinal chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

What it found

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Yanfang ZhaoKey Laboratory of Tumor Immunological Prevention and Treatment, Department of Oncology, Yan'An Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, China.
Wanbao DingKey Laboratory of Tumor Immunological Prevention and Treatment, Department of Oncology, Yan'An Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, China.
Peixian ZhangKey Laboratory of Tumor Immunological Prevention and Treatment, Department of Oncology, Yan'An Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, China.
Lei DengKey Laboratory of Tumor Immunological Prevention and Treatment, Department of Oncology, Yan'An Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, China.
Yi LongKey Laboratory of Tumor Immunological Prevention and Treatment, Department of Oncology, Yan'An Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, China.
Jiuqin LuKey Laboratory of Tumor Immunological Prevention and Treatment, Department of Oncology, Yan'An Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, China.ORCID 0009-0003-4584-9892
Fereshteh ShiriDepartment of Chemistry, University of Zabol, Zabol, Iran.
Mostafa Heidari MajdDepartment of Medicinal Chemistry, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran.ORCID 0000-0003-3461-832X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlthough tamoxifen (TMX) belongs to selective estrogen receptor modulators (SERMs) and selectively binds to estrogen receptors, it affects other estrogen-producing tissues due to passive diffusion and non-differentiation of normal and cancerous cells and leads to side effects.

methodsThe problems expressed about tamoxifen (TMX) encouraged us to design a new drug delivery system based on magnetic nanoparticles (MNPs) to simultaneously target two receptors on cancer cells through folic acid (FA) and hyaluronic acid (HA) groups. The mediator of binding of two targeting agents to MNPs is a polymer linker, including dopamine, polyethylene glycol, and terminal amine (DPN).

resultsZeta potential, dynamic light scattering (DLS), and Field emission scanning electron microscopy (FESEM) methods confirmed that MNPs-DPN-HA-FA has a suitable size of ~105 nm and a surface charge of -41 mV, and therefore, it can be a suitable option for carrying TMX and increasing its solubility. The cytotoxic test showed that the highest concentration of MNPs-DPN-HA-FA-TMX decreased cell viability to about 11% after 72 h of exposure compared to the control. While the protective effect of modified MNPs on normal cells was evident, unlike tamoxifen, the survival rate of liver cells, even after 180 min of treatment, was not significantly different from the control group. The protective effect of MNPs was also confirmed by examining the amount of malondialdehyde, and no significant difference was observed in the amount of lipid peroxidation caused by modified MNPs compared to the control. Flow cytometry proved that TMX loaded onto modified MNPs can induce apoptosis by targeting the overexpressed receptors on cancer cells. Real-time PCR showed that the modified MNPs activated the intrinsic and extrinsic mitochondrial pathways of apoptosis, so the Bak1/Bclx ratio for MNPs-DPN-HAFA- TMX and free TMX was 70.82 and 0.38, respectively. Also, the expression of the caspase-3 gene increased 430 times compared to the control. On the other hand, only TNF gene expression, which is responsible for metastasis in some tumors, was decreased by both free TMX and MNPs-DPN-HA-FA-TMX. Finally, molecular docking proved that MNPs-DPN-HA-FA-TMX could provide a very stable interaction with both CD44 and folate receptors, induce apoptosis in cancer cells, and reduce hepatotoxicity.

conclusionAll the results showed that MNPs-DPN-HA-FA-TMX can show good affinity to cancer cells using targeting agents and induce apoptosis in metastatic breast ductal carcinoma T-47D cell lines. Also, the protective effects of MNPs on hepatocytes are quite evident, and they can reduce the side effects of TMX.

Indexed as

ApoptosisCell SurvivalDrug Screening Assays, AntitumorTamoxifenAntineoplastic Agents, HormonalCell ProliferationDose-Response Relationship, DrugDrug Delivery SystemsFolic AcidHep G2 CellsHumansHyaluronic AcidLiverMagnetite NanoparticlesMolecular StructureParticle SizeAntineoplastic Agents, HormonalFolic AcidHyaluronic AcidMagnetite NanoparticlesTamoxifenBcl-2 family proteinsdrug deliveryflow cytometryhepatotoxicity.hyaluronic acidMagnetic nanoparticlesreal time PCR

Identifiers

PMID38685808

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.