Platelet-cloaked alginate-poly (β-amino ester) a novel platform bioinspired polyelectrolyte nanoparticle for targeted delivery of carboplatin in breast cancer: An in vitro/in vivo study

Abstract

Triple-negative breast cancer (TNBC) has poor prognosis. Carboplatin (Crb) is a widely used chemotherapeutic agent, in TNBC but with serious systemic toxicity and poor tumor targeting. Bioinspired drug-loaded platelets (Plt) and Plt-coated nanocarriers evade macrophage phagocytosis by membrane proteins like CD47. The goal of this study was preparation of a novel alginate-poly (R-amino ester) (PRAE) nanoparticles (NPs) for targeted delivery of Crb to TNBC cells by developing and comparison of two bioinspired carriers of Plt membrane (PltM) coated Crb-loaded alginate-poly (beta-amino ester) nanoparticles (PltM@Crb-PRAE-ALG NPs) and Plt loaded Crb (Plt@Crb). The NPs were prepared by ionic gelation and subsequently were coated by platelet membrane using ultra-sonication method. The loading efficiency, release profile, and in vitro cytotoxicity of both formulations were evaluated on HUVEC and 4 T1 cells. Additionally, the in vivo tumor targeting, therapeutic efficacy, and organ toxicity of the two formulations were assessed in a murine tumor model. Results showed both Plt@Crb and (PltM@Crb-P beta AE-ALG NPs) exhibited high drug loading efficiency, sustained release, enhanced cytotoxicity against 4 T1 cells, and decreased cytotoxicity in normal cells (HUVEC) in vitro. . In vivo studies revealed that although both formulations considerably improved tumor inhibition compared to free Crb, but the PltM@CrbP beta AE-ALG NPs demonstrated superior cytotoxicity and therapeutic efficacy, thanks to improved Crb's internalization efficiency, enhanced stability, and controlled release properties.