Ultrasound-activated particles as CRISPR/Cas9 delivery system for androgenic alopecia therapy.

Compared to a plasmid, viral, and other delivery systems, direct Cas9/sgRNA protein delivery has several advantages such as low off-targeting effects and non-integration, but it still has limitations due to low transfer efficiency. As such, the CRISPR/Cas9 system is being developed in combination with nano-carrier technology to enhance delivery efficiency and biocompatibility. We designed a microbubble-nanoliposomal particle as a Cas9/sgRNA riboprotein complex carrier, which effectively facilitates local delivery to a specific site when agitated by ultrasound activation. In practice, we successfully transferred the protein constructs into dermal papilla cells in the hair follicle of androgenic alopecia animals by microbubble cavitation induced sonoporation of our particle. The delivered Cas9/sgRNA recognized and edited specifically the target gene with high efficiency in vitro and in vivo, thus recovering hair growth. We demonstrated the topical application of ultrasound-activated nanoparticles for androgenic alopecia therapy through the suppression of SRD5A2 protein production by CRISPR-based genomic editing.

Ions doped melanin nanoparticle as a multiple imaging agent.

BACKGROUND: Multimodal nanomaterials are useful for providing enhanced diagnostic information simultaneously for a variety of in vivo imaging methods. According to our research findings, these multimodal nanomaterials offer promising applications for cancer therapy. RESULTS: Melanin nanoparticles can be used as a platform imaging material and they can be simply produced by complexation with various imaging active ions. They are capable of specifically targeting epidermal growth factor receptor (EGFR)-expressing cancer cells by being anchored with a specific antibody. Ion-doped melanin nanoparticles were found to have high bioavailability with long-term stability in solution, without any cytotoxicity in both in vitro and in vivo systems. CONCLUSION: By combining different imaging modalities with melanin particles, we can use the complexes to obtain faster diagnoses by computed tomography deep-body imaging and greater detailed pathological diagnostic information by magnetic resonance imaging. The ion-doped melanin nanoparticles also have applications for radio-diagnostic treatment and radio imaging-guided surgery, warranting further proof of concept experimental.