Supramolecular micellar drug delivery system based on multi-arm block copolymer for highly effective encapsulation and sustained-release chemotherapy.

Poly(phosphoester)-based biomaterials have great potential in drug delivery systems (DDSs) because of their multifunctional adjustability, stealth effect, excellent biodegradability, and biocompatibility. To further increase the drug loading efficiency (DLE) and sustained release ability, a multi-arm block copolymer, poly(amido amine)-b-poly(2-butenyl phospholane)-b-poly(2-methoxy phospholane) conjugated with folic acid (abbreviated as PAMAM-PBEP-PMP-FA), was designed and prepared. Compared to the traditional linear copolymers, this multi-arm phosphoester block copolymer integrates a balanced combination of unique features. As an advanced DDS, the PAMAM-PBEP-PMP-FA based supramolecular micelle provides good architectural stability, low protein adsorption, extremely high DLE, and sustained drug release for chemotherapy and abundant surface chemistry for target engineering. Benefitting from these novel functions, the supramolecular micellar drug delivery system exhibits great performances both in in vitro and in vivo evaluations. Doxorubicin (DOX)-loaded supramolecular micelles PAMAM-PBEP-PMP-FA/DOX are fast taken up by HepG2 cells and inhibit the tumor growth effectively in HepG2-tumor-bearing nude mice without obvious system toxicity. This work not only suggests a targeted sustained release DDS for effective chemotherapy but also enlightens, through a delicate design at the molecular scale, the brilliance of multifunctional PPE-based nanomaterials towards versatile bio-applications.