Anti HER-2 aptamer functionalized gold nanoparticles of dasatinib for targeted chemo-radiotherapy in breast cancer cells

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In the present study, gold nanoparticles functionalized with anti HER-2 aptamer were designed for effective targeted delivery of dasatinib (DSB) to breast cancer cells. Anti HER-2 aptamer attached to porous or plain gold nanoparticles were compared for dasatinib delivery. Activated drug with succinic anhydride and L-cysteine linker was used for conjugation of DSB to gold nanoparticles. The loading efficiency of the activated drug on plain and porous gold nanoparticles was 52 and 68 %, respectively, which was significantly more than the loading of free DSB in gold nanoparticles (1-2.5 %). The anti HER-2 aptamer was conjugated to porous gold nanoparticles loaded with the activated drug. Various characterization techniques such as FESEM, TEM, AFM, zeta potential and ICP-MS were used to confirm the binding of the drug to gold nanoparticles. 1HNMR and FTIR spectroscopic analyses were employed to examine the structural characteristics of the conjugated drug. These analytical techniques confirmed the successful incorporation of succinyl and thiol groups onto the drug molecule. The amount of aptamer binding to different types of gold nanoparticles was obtained from the intensity of the light emitted from the bands observed in electrophoresis gel and due to the presence of porosity in porous gold nanoparticles, the amount of aptamer conjugation on porous gold nanoparticles increased compared to plain ones. Cell cytotoxicity and cellular uptake were evaluated by MTT assay and TEM in BT-474 and MCF-7 cells. Aptamer-functionalized porous gold nanoparticles containing activated dasatinib showed higher cytotoxicity and cellular uptake than modified DSB-loaded nanoparticles and un-activated DSB. The combination of radiation therapy with the modified dasatinib attached to porous gold nanoparticles and aptamer demonstrated a notable reduction in the IC50 values for both the BT-474 and MCF-7 cell lines. Specifically, the IC50 value for the BT-474 cells decreased from 6.95 μM (for unmodified dasatinib) to 2.57 μM, while for the MCF-7 cells, it decreased from 13.97 μM to 8.57 μM. These findings indicate a significant improvement in the efficacy of the modified dasatinib compared to its unmodified counterpart when used in conjunction with radiation therapy.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:154

Enthalten in:

Biomaterials advances - 154(2023) vom: 15. Nov., Seite 213591

Sprache:

Englisch

Beteiligte Personen:

Khorshid, Mahdis [VerfasserIn]
Varshosaz, Jaleh [VerfasserIn]
Rostami, Mahboubeh [VerfasserIn]
Haghiralsadat, Fateme [VerfasserIn]
Akbari, Vajihe [VerfasserIn]
Khorshid, Pardis [VerfasserIn]

Links:

Volltext

Themen:

7440-57-5
Anti HER-2 aptamer
Aptamers, Nucleotide
Breast cancer
Dasatinib
Gold
Gold nanoparticles
Journal Article
RBZ1571X5H
Radiotherapy

Anmerkungen:

Date Completed 13.11.2023

Date Revised 13.11.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.bioadv.2023.213591

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM361098782