Folic Acid–Modified miR-491-5p–Loaded ZIF-8 Nanoparticles Inhibit Castration-Resistant Prostate Cancer by Regulating the Expression of EPHX1

Abstract

Epoxide hydrolase 1 (EPHX1) has been reported to be related to the development of several tumors. However, the regulation of castration-resistant prostate cancer (CRPC) development by EPHX1 has not been reported. We used proteomic technology and found that the EPHX1 protein was highly expressed in CRPC tissues and the CRPC cell line C4-2. We performed screening and found that EPHX1 is a direct target of miR-491-5p. High miR-491-5p expression significantly reduced the EPHX1 level in C4-2 cells and inhibited C4-2 cell proliferation and migration. Zeolite imidazolate framework-8 (ZIF-8) has good thermal stability, a simple synthesis method, tumor site stability, and specific acid responsiveness. We synthesized ZIF-8 nanodrug vectors to deliver miR-491-5p into C4-2 cells. After loading miR-491-5p into ZIF-8, we modified the ZIF-8 surface with folic acid (FA) as the target group (FA@ZIF-8). Our synthesized nanodrug carrier showed less cytotoxicity to C4-2 cells even at 200 μg/ml. Modified FA could increase the efficiency of nanomaterial entry into C4-2 cells. FA@miR-491-5p@ZIF-8 could stably release miR-491-5p for a long period in both phosphate-buffered saline (pH 7.4) and acetate buffer (pH 4.8), and miR-491-5p was released faster at the beginning of the experiment in acetate buffer (pH 4.8). FA@miR-491-5p@ZIF-8 significantly reduced C4-2 cell proliferation and migration, and FA@miR-491-5p@ZIF-8 had a better effect than miR-491-5p alone. In vivo, FA@miR-491-5p@ZIF-8 significantly inhibited CRPC growth in nude mice. Overall, we verified that miR-491-4p regulated CRPC development by targeting EPHX1. The drug nanocarrier FA@miR-491-5p@ZIF-8 not only significantly reduced C4-2 CRPC cell proliferation and migration but also significantly inhibited CRPC growth. Our research provides a theoretical basis for treatment and treatment strategies for CRPC.

Debridement of contaminated implants using air-polishing coupled with pH-responsive maximin H5-embedded metal-organic frameworks

“…The antimicrobial activities of MH5C@ZIF-8 NPs primarily depended on the antibacterial peptides and zinc ions released to inflammation sites along with the hydrolysis and collapses of the whole frameworks ( Ju et al, 2021 ; Wan et al, 2021 ). In detail, with the help of sustained released peptides and metal ions, the cell membranes, the membrane potentials, and the ion homeostasis were initially interrupted, causing obvious membrane dyshomeostasis, membrane permeability, and leakages of the cell component ( Figure 1B ) ( Wen et al, 2021 ; Han et al, 2022 ).…”

Genetic Signatures for Distinguishing Chemo-Sensitive from Chemo-Resistant Responders in Prostate Cancer Patients

“…UGT1A6’s role in the metabolic inactivation of drug therapies is well-established [ 30 ]. EPHX1 overexpression is noted in castration-resistant prostate cancer [ 31 ].…”

ZIF-8/Curcumin-Loaded Electrospun Nanofiber Membrane for Wound Healing

“…Compared with conventional nanoscale drug carriers, ZIF-8 possesses a larger specific surface area, higher porosity, and significantly higher drug-loading efficiency. 13,14 Moreover, it can remain stable under physiological conditions but break down under acidic conditions, enabling controlled drug release. 15 Notably, when ZIF-8 disintegrates, it continuously releases Zn 2+ , which is an excellent antibacterial agent.…”

“…The coordination of zinc (Zn) ions (Zn 2+ ) with 2-methylimidazole results in the formation of a zeolitic imidazolate framework-8 (ZIF-8), which exhibits good biocompatibility and acid-environment sensitivity. Compared with conventional nanoscale drug carriers, ZIF-8 possesses a larger specific surface area, higher porosity, and significantly higher drug-loading efficiency. , Moreover, it can remain stable under physiological conditions but break down under acidic conditions, enabling controlled drug release . Notably, when ZIF-8 disintegrates, it continuously releases Zn 2+ , which is an excellent antibacterial agent.…”