Berberine-based self-assembly agents with enhanced synergistic antitumor efficacy

Area of Science:

• Nanomedicine
• Natural Product Chemistry
• Oncology

Background:

• Tumors remain a significant global health challenge, necessitating improved therapeutic strategies.
• Existing nanodrug delivery systems often face limitations including complex preparation, low drug loading, untargeted release, and inherent toxicity.
• Natural products from medicinal plants offer diverse scaffolds for developing novel antitumor drugs.

Purpose of the Study:

• To develop innovative, carrier-free berberine (BBR)-based nanoparticles (NPs) for enhanced synergistic tumor treatment.
• To investigate the self-assembly mechanisms and antitumor mechanisms of BBR-GA and BBR-ART NPs.
• To evaluate the in vitro and in vivo antitumor efficacy and targeting capabilities of the developed NPs.

Main Methods:

• Self-assembly of two carrier-free BBR-based NPs: BBR-GA and BBR-ART, driven by electrostatic and hydrophobic interactions.
• Investigation of BBR-GA NPs' mechanism involving mitochondria-mediated apoptosis via regulation of mitochondrial fission and dysfunction.
• Analysis of BBR-ART NPs' mechanism inducing ferroptosis in tumor cells.
• In vitro and in vivo evaluation of NP targeting and antitumor properties.

Main Results:

• Successful formation of carrier-free BBR-GA and BBR-ART NPs through self-assembly.
• BBR-GA NPs induced mitochondria-mediated apoptosis, while BBR-ART NPs triggered ferroptosis in tumor cells.
• BBR-based NPs demonstrated superior tumor targeting and enhanced antitumor efficacy compared to simple monomer mixtures, both in vitro and in vivo.

Conclusions:

• Carrier-free self-assemblies of natural products offer a viable strategy for synergistic drug delivery.
• These BBR-based NPs present a promising platform for developing advanced antitumor therapeutics.
• The study highlights the potential of natural product-derived nanostructures for overcoming limitations of traditional nanocarriers.