CD38-targeted and erythrocyte membrane camouflaged nano-drug delivery system for photothermal-chemotherapy in multiple myeloma

Abstract

AbstractBackground: Multiple myeloma (MM) is a malignant and incurable disease. Currently, chemotherapy is the primary approach for the treatment of MM. Bortezomib (BTZ) is a breakthrough drug for MM, significantly improving patient survival. However, BTZ can interrupt the treatment due to its serious side effects. Therefore, developing novel therapeutics for MM is essential. Herein, an innovative nanoparticle-based drug delivery system P-R@Ni3P-BTZ is designed and constructed to treat MM. The present study investigated the feasibility, effectiveness, and safety of P-R@Ni3P-BTZ in vitro and in vivo. Results: Trinickel monophosphide nanoparticles (Ni3P NPs) are spherical porous hollow materials with photothermal performance. As a novel scaffold, Ni3P integrates photothermal therapy (PTT) with chemotherapy by loading BTZ (Ni3P-BTZ). In addition, Ni3P-BTZ is wrapped by a thin layer of the red blood cell membrane (Rm) to form R@Ni3P-BTZ, which confers the enhanced permeability and retention (EPR) effect and reduces immunogenicity. Finally, CD38-targeting peptide P is inserted into Rm via DSPE-PEG2000-P to precisely target MM cells (P-R@Ni3P-BTZ). In vitro and in vivo, it proved that P-R@Ni3P-BTZ has excellent targeting ability to CD38 + MM cells and is highly effective in killing MM cells. P-R@Ni3P-BTZ significantly induces the accumulation of intracellular reactive oxygen species (ROS) levels and increases apoptosis of MM cells, which underlies the primary mechanism of antitumor effects. In addition, in vitro and in vivo experiments proved that P-R@Ni3P possesses good biocompatibility and biosafety. Conclusions: These findings suggested that P-R@Ni3P-BTZ nanodrug delivery system is a promising CD38 targeting chemotherapy and PTT nanocomposites, which is a specific and efficient MM therapeutic method.