One-step and facile synthesis of peptide-like poly(melphalan) nanodrug for cancer therapy

The clinical applications of polymer-based nanomedicines have been restricted by their complicated synthesis processes, biosafety issues, and uncontrollable drug loading. In this study, we developed a peptide-like polydrug for cancer chemotherapy using the FDA-approved drug melphalan via a simple one-step synthesis strategy. The prepared poly (melphalan) (PMP)-PEG was characterized through standard methods and formulated into sub-100 nm nanoparticles using the nanoprecipitation method. The poly (melphalan)-PEG nanoparticles (PMP NPs) showed controllable drug loading (up to 70 wt%) with high stability in buffers. In vitro cell viability studies showed good cell uptake behavior and high cytotoxicity of the PMP-NPs compared to Evomela controls (a commercial and clinical melphalan formulation). For in vivo mouse models tests, the PMP-NPs could accumulate in the tumor sites for ≥ 1 week and effectively inhibited tumor growth with minimal side-effects. This peptide synthesis strategy and a melphalan based polydrug nanoplatform may be promising for new drug development and effective cancer therapy.