Carrier-free multi-components self-delivery nanocomplex for tumor synergistic therapy

Due to the intricate nature of tumors, developing multidrug delivery system to enhance synergistic therapy for tumors is urgently needed. Herein, we present a carrier-free nanocomplex (DHT NC@SF MPN), consisting of dihydrotanshinone-1 nanocrystals (DHT NC) combined with silybin-ferric metal-phenolic network coatings (SF MPN), for multidrug self-delivery and chemo/chemodynamic synergistic cancer therapy. The generated nanocomplex (DHT NC@SF MPN) was completely composed of three therapeutic ingredients: DHT (56.08 %), Sil (41.88 %), and Fe(III) (2.01 %) without incorporation of any nano-materials. It displayed spherical core-shell structure with particle size 262 nm and acid responding drug release. The nanocomplex could be efficiently uptaken by HGC-27 tumor cells through the lipid raft/caveolin mediated pathway. It exhibited stronger tumor cell proliferation inhibition, migration inhibition, cell apoptosis and ferroptosis compared with free drugs. On tumor bearing mice, it showed comparable anti-tumor efficacy with the commercial paclitaxel liposome while systemic toxicity was negligible. Therefore, the facile nanocarrier-free multidrug self-delivery nanoplatform shed light on developing advanced nanomedicine for tumor synergistic therapy.