<p>CD44-Targeted Magnetic Nanoparticles Kill Head And Neck Squamous Cell Carcinoma Stem Cells In An Alternating Magnetic Field</p>

Abstract

BackgroundHead and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor in the world. Studies in recent years have demonstrated that cancer stem cells (CSCs) are present in many tumor tissues, including HNSCC, and CSCs are the root cause of tumor recurrence and metastasis. Thus, taking new treatment measures to target the killing of CSCs that are resistant to chemotherapy and radiotherapy is key to the success of cancer treatment.MethodsWe explored a method for preparing anti-CD44 antibody-modified superparamagnetic iron oxide nanoparticles (SPIONPs). Biocompatibility was evaluated by a CCK-8 assay. The CSCs were obtained by a 3D cell culture technique from Cal-27 (human oral squamous cell carcinoma) cells, and then the CSCs were identified by quantitative real-time polymerase chain reaction (qRT-PCR). The targeting efficiency of the CD44-SPIONPs to CSCs was confirmed by Prussian blue staining and visualized by laser scanning confocal microscopy (LSCM). Flow cytometry was used to detect the apoptosis of CSCs after alternating magnetic field (AMF) treatment. The efficacy of tumor growth inhibition by CD44-SPIONP-mediated magnetic hyperthermia therapy was evaluated with tumor xenografts in nude mice.ResultsThe CD44-SPIONPs exhibited no negative effect on CSCs, indicating good biocompatibility. After SPIONPs were cocultured with stem cells, the majority of CD44-SPIONPs labeled with FITC penetrated the cell membrane into the cytoplasm. After AMF treatment, CD44-SPIONPs induced CSCs to undergo programmed death. The inhibitory ratio of the treated group was 33.43%, and necrotic areas in the tumor tissue were mainly distributed around the magnetic fluid.ConclusionThese results demonstrate that it is possible to kill CSCs using targeted magnetic nanoparticles and an AMF and that magnetic fluid hyperthermia significantly inhibited the growth of grafted Cal-27 tumors in mice.

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

“…GPI-APs such as the folate receptor (FR) and CD44 have also been frequently targeted due to their important roles in tumor growth and migration [ 198 , 199 ]. Ligands for the FR (e.g., folate) and CD44 (e.g., hyaluronic acid, CD44 antibodies) have been, therefore, widely used along with IONs for tumor targeting both in vitro and in vivo [ 200 , 201 , 202 , 203 ]. Although these receptors are commonly internalized through lipid raft-dependent mechanisms (e.g., CLIC/GEEC pathway), recent reports have also described the contribution of CME [ 204 , 205 ].…”

The Intrinsic Biological Identities of Iron Oxide Nanoparticles and Their Coatings: Unexplored Territory for Combinatorial Therapies

“…These complex interactions between the biological milieu and the nanoparticle depend on multiple factors such as synthetic identity, the biological microenvironment, and the interaction time with the organism. The possibility of functionalizing IONPs with biomolecules such as peptides [ 14 , 15 ], ligands [ 16 ], antibodies [ 17 , 18 ], aptamers [ 19 , 20 ], or RNAs [ 21 ] further enables IONPs to interact with a specific cell type or tissue; for instance, antibody-functionalized IONPs can specifically target antigen-expressing tumor cells, which allows local application of an alternative magnetic field for the induction of magnetic hyperthermia [ 22 ]. Understanding these interactions and how they influence the intended application of the synthesized nanoparticle is critical, as such knowledge not only allows for more rational nanomaterial design but could also enable these previously undiscovered characteristics to be harnessed for combinatorial therapies.…”

<p>^99mTc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation</p>

“…HA can target to CD44-overexpressed solid cancer and cancer stem cells, such as breast, lung, and prostate cancers. [23][24][25][26][27][28] By modifying hydrophobic segments, HA-derivatives could self-assemble into nanoparticles that could be used for chemotherapeutics delivery. 29,30 For instance, Jeannot et al reported HA-b-poly(γ-benzyl-L-glutamate) nanoparticles that could actively target to the CD44 receptor for delivery of vorinostat and gefitinib with strong tumor growth inhibition.…”