A Novel Method of Magnetic Nanoparticles Functionalized with Anti-Folate Receptor Antibody and Methotrexate for Antibody Mediated Targeted Drug Delivery

Abstract

Therapeutic effects of anticancer medicines can be improved by targeting the specific receptors on cancer cells. Folate receptor (FR) targeting with antibody (Ab) is an effective tool to deliver anticancer drugs to the cancer cell. In this research project, a novel formulation of targeting drug delivery was designed, and its anticancer effects were analyzed. Folic acid-conjugated magnetic nanoparticles (MNPs) were used for the purification of folate receptors through a novel magnetic affinity purification method. Antibodies against the folate receptors and methotrexate (MTX) were developed and characterized with enzyme-linked immunosorbent assay and Western blot. Targeting nanomedicines (MNP-MTX-FR Ab) were synthesized by engineering the MNP with methotrexate and anti-folate receptor antibody (anti-FR Ab). The cytotoxicity of nanomedicines on HeLa cells was analyzed by calculating the % age cell viability. A fluorescent study was performed with HeLa cells and tumor tissue sections to analyze the binding efficacy and intracellular tracking of synthesized nanomedicines. MNP-MTX-FR Ab demonstrated good cytotoxicity along all the nanocomposites, which confirms that the antibody-coated medicine possesses the potential affinity to destroy cancer cells in the targeted drug delivery process. Immunohistochemical approaches and fluorescent study further confirmed their uptake by FRs on the tumor cells’ surface in antibody-mediated endocytosis. The current approach is a useful addition to targeted drug delivery for better management of cancer therapy along with immunotherapy in the future.

Methotrexate Induces an Antioxidant Hormetic Response in Primary Rat Astrocytes

“…High doses of MTX have been reported to generate a state of oxidative stress capable of damaging biomolecules, inducing cancer cells death 38 ; this mechanism is independent on folic acid conversion to tetrahydrofolate by inhibiting the dehydrofolate reductase (DHFR) activity, an essential enzyme in DNA synthesis mechanisms. 38 , 39 On the other hand, treatment with low concentrations of MTX is known to reduce inflammation, decrease apoptosis, and induce proliferation by inhibiting NF-κB and PI3K/Akt. 40 Studies using HUVEC cells treated with TNF-α have shown that low concentrations of MTX induce the expression of survival genes such as SOD-Mn, OH-1, UCP-2, which are regulated by AMPK-CREB.…”

Chitosan-Based Nano-Smart Drug Delivery System in Breast Cancer Therapy

“…FR-based delivery vehicles are internalized by target cells through receptor-mediated endocytosis. As a result, drug-loaded nanocarriers may be tailored to target particular cancer cell receptors, employing targeting ligands such as folic acid (FA) [ 41 , 42 , 43 ]. FA is a well-known vitamin for cell proliferation and biomarker targeting.…”

Metal and Metal Oxides Nanoparticles and Nanosystems in Anticancer and Antiviral Theragnostic Agents

“…The utilization of antibody-bound MIONPs hinted at the potential to create a targeted thermal treatment for metastatic cancer by means of induction heating with an external alternating magnetic field. Tests were conducted employing (111) In-ChL6 bio-probes (a chimeric L6) in an artificial xenograft model for human breast cancer [82]. Another [83] examination administered Herceptin (trastuzumab) to transport ferric oxide-enriched NPs to Human Epidermal Growth Factor Receptor 2 (HER-2+) cancer cells.…”