In vivo metabolizable branched poly(ester amide) based on inositol and amino acids as a drug nanocarrier for cancer therapy.

Amino acid-based poly(ester amide) (PEA) has been utilized for various biomedical applications due to its tunable mechanical properties, good biocompatibility, and biodegradability. However, bioactive components have rarely been incorporated into the PEA structure, and there has been no systematic investigation of amino acid-based PEAs with branched structures. Herein, an in vivo metabolizable branched poly(ester amide) (BPEA) was synthesized from inositol (a natural growth factor) and amino acids for drug delivery in cancer therapy. The bioactive components, inositol, arginine, and phenylalanine, could improve the biocompatibility of the BPEA nanocarrier, and convert into other valuable biomolecules (phosphatidylinositol for cell signaling, functional protein, or other amino acids including ornithine, citrulline, and tyrosine) after accomplishing drug delivery and biodegradation. Paclitaxel (PTX) was encapsulated into BPEA nanocarriers to formulate drug-loaded BPEA nanoparticles (BPEA@PTX NPs). In vitro results indicated that BPEA@PTX NPs had a sub 100 nm size and could effectively inhibit the growth and migration of cancer cells. In vivo experiments further demonstrated significant suppression of tumor size compared with that with free PTX. Both in vitro and in vivo results confirmed the superior biosafety of BPEA, indicating that BPEA exhibits excellent biocompatibility and considerable potential as a drug carrier.