Role of HIKESHI on Hyperthermia for Castration-Resistant Prostate Cancer and Application of a Novel Magnetic Nanoparticle with Carbon Nanohorn for Magnetic Hyperthermia

Abstract

The prognosis of castration-resistant prostate cancer (CRPC) is technically scarce; therefore, a novel treatment for CRPC remains warranted. To this end, hyperthermia (HT) was investigated as an alternative therapy. In this study, the analysis focused on the association between CRPC and heat shock protein nuclear import factor “hikeshi (HIKESHI)”, a factor of heat tolerance. Silencing the HIKESHI expression of 22Rv1 cells (human CRPC cell line) treated with siRNAs inhibited the translocation of heat shock protein 70 from the cytoplasm to the nucleus under heat shock and enhanced the effect of hyperthermia. Moreover, a novel magnetic nanoparticle was developed via binding carbon nanohorn (CNH) and iron oxide nanoparticle (IONP) with 3-aminopropylsilyl (APS). Tumor-bearing model mice implanted with 22 Rv1 cells were examined to determine the effect of magnetic HT (mHT). We locally injected CNH-APS-IONP into the tumor, which was set under an alternative magnetic field and showed that tumor growth in the treatment group was significantly suppressed compared with other groups. This study suggests that HIKESHI silencing enhances the sensitivity of 22Rv1 cells to HT, and CNH-APTES-IONP deserves consideration for mHT.

In Vitro Study of Tumor-Homing Peptide-Modified Magnetic Nanoparticles for Magnetic Hyperthermia

“…Magnetic nanoparticles (MNPs) can play a crucial role in enabling localized heating within a short period of time [ 8 ]. Due to their biocompatibility and superparamagnetic properties, MNPs are used to induce magnetic hyperthermia by applying an alternating magnetic field (AMF) [ 9 , 10 , 11 ]. In recent years, diverse surface-modified MNPs [ 12 ] and bioconjugated MNPs with proteins and antibodies, including folate receptor, trastuzumab, and immunoglobulin G [ 13 ], have been reported to improve the therapeutic performance of MNPs during hyperthermia.…”

A Multifunctional Nanocatalytic Metal-Organic Framework as a Ferroptosis Amplifier for Mild Hyperthermia Photothermal Therapy

“…Recently, mild PTT (below 43 °C) has emerged as an alternative to overcome this controversial issue of conventional HTT [ 10 – 12 ]. Unfortunately, at only 5 °C above body temperature, self-protection pathways in cancer cells can be activated to repair fever-type cell damage via the overexpression of heat shock proteins (HSPs) to increase heat tolerance [ 13 – 15 ]. To alleviate thermotolerance, various HSP inhibition strategies, including the use of triptolide, STA-9090, and gambogic acid [ 16 , 17 ], have been utilized to amplify the therapeutic efficacy of mild PTT [ 18 , 19 ].…”

A Paramagnetic Metal‐Organic Framework Enhances Mild Magnetic Hyperthermia Therapy by Downregulating Heat Shock Proteins and Promoting Ferroptosis via Aggravation of Two‐Way Regulated Redox Dyshomeostasis

“…[1][2][3] However, the therapeutic efficacy of MMHT is severely DOI: 10.1002/advs.202306178 limited due to thermo-resistance caused by the increase in heat shock proteins (HSPs) as a result of the treatment. [4] To date, two methods have been reported to downregulate HSPs to enhance MMHT. The first method is to inhibit the biosynthesis of HSPs using inhibitors, siRNA, or reducing the energy supply (e.g., adenosine triphosphate (ATP)).…”