Anti-FGFR1 aptamer-tagged superparamagnetic conjugates for anticancer hyperthermia therapy

Abstract

Compounds that recognize and strongly bind to molecular targets are one of the cornerstones of modern pharmaceutics. Work has been ongoing for the past 25 years on the therapeutic use of aptamers, nucleic acid molecules, whose three-dimensional structure is the result of interactions between complementary base pairs. The aptamers selection methods allow the oligonucleotides which bind the molecular target in its native environment to be quickly isolated from a large library of random oligonucleotides. The possibilities presented for aptamers in the field of targeted therapy require the application of effective carriers to counter the renal clearance effect and/or functional cargo to exert therapeutic action if the aptamer is only used as a targeting moiety. Lately, a material gaining ground in biomedical research is iron oxide particles, which exhibit a superparamagnetic characteristic at nanoscale levels. This allows the iron oxide nanoparticles to convert external magnetic energy into heat, a mechanism known as hyperthermy, and efficiently supports conventional oncological treatment. In this study, we describe an experimentally confirmed functional model of targeted anticancer hyperthermia therapy. Using the systematic evolution of ligands by exponential enrichment technique, we selected a DNA aptamer that specifically binds to the extracellular domain of recombinant fibroblast growth factor receptor type-1 (FGFR1) with a nanomolar dissociation constant. The chosen target plays an important role in many crucial cellular processes and is also considered a candidate protein that is involved in tumor initiation, survival and progression. Next, we combined the selected aptamer with iron oxide nanoparticles to produce aptamer superparamagnetic conjugates (ASCs). Finally, we found that targeted ASCs selectively destroy FGFR1-overexpressing human osteosarcoma cells U2OS upon magnetic field irradiation.

Comparative effects of magnetic and water-based hyperthermia treatments on human osteosarcoma cells

“…1 However, the most studied HT method for medical applications is by far magnetic hyperthermia based on magnetic nanoparticles prepared by different physical and chemical methods. [2][3][4][5][6] Treatment efficiency is mainly influenced by the heating time and temperature levels achieved during the HT process, the lethal effect depending on the temperature induced in the targeted regions, exposure time to heat, 1 and type of cancer cells.…”

EpCAM aptamer-functionalized polydopamine-coated mesoporous silica nanoparticles loaded with DM1 for targeted therapy in colorectal cancer

“…17 Given their properties, APts have attracted much attention as molecular probes for cancer cell detection and targeted cancer therapy. [18][19][20][21] Epithelial cell adhesion molecule (EpCAM) APt is one of the DNA APts can specifically bind to EpCAM with high affinity. 22 EpCAM (CD326), a 40 kDa transmembrane glycoprotein, is overexpressed in most rapidly proliferating tumors of epithelial origin, while at a variable but generally lower level in the normal epithelium.…”

Recent Advancements of Magnetic Nanomaterials in Cancer Therapy

“…Tumor ablation therapies with MNPs are generating major interest including (a) magnetic hyperthermia (necrotic tumor destruction by heat generated from MNPs upon alternating external magnetic field); (b) photothermal therapy (cancer cell death by the heat generated from MNPs upon light) and (c) photodynamic therapy (cancer cell death using cytotoxic singlet oxygen species generated from MNPs conjugated with photosensitizing agent) (Figure 2a-c) [31,[92][93][94][95]. J. Kolosnjaj-Tabi, and coworkers, showed the outstanding tumor regression in mouse epidermoid carcinoma xenograft model using PEG-coated magnetite NPs after magnetic hyperthermia [96].…”

“…Moreover, antibody conjugation with MNPs enhanced the effect of hyperthermia because of the anticancer effects of the antibody and selectivity of the cancer cells. Examples include anti-FGFR1 aptamer-tagged MNPs for enhanced magnetic hyperthermia and antibody-conjugated MNPs for enhanced anti-cancer effects of Cryptotanshinone [92,93]. Magnetic hyperthermia combined with chemotherapy demonstrated enhanced tumor regression ability.…”