Macrophage-Membrane-Coated Nanoparticles for Tumor-Targeted Chemotherapy

TLDR

Biologically derived membrane systems have been employed to extend delivery vector residence time and reduce reticuloendothelial system clearance during systemic circulation. The study aims to rationally design chemo‑drug‑loaded membrane delivery systems with improved tumor‑site penetration and controlled release. The macrophage membrane coating enables tumor homing and RES evasion, then sheds via microenvironment‑driven morphological changes. The macrophage‑membrane‑coated nanoparticle (cskc‑PPiP/PTX@Ma) shows enhanced tumor penetration due to size and surface modifications, rapid drug release in acidic endosomes, and superior therapeutic efficacy from tumor homing and step‑wise controlled release, demonstrating an effective, tumor‑microenvironment‑responsive delivery system.

Abstract

Various delivery vectors have been integrated within biologically derived membrane systems to extend their residential time and reduce their reticuloendothelial system (RES) clearance during systemic circulation. However, rational design is still needed to further improve the in situ penetration efficiency of chemo-drug-loaded membrane delivery-system formulations and their release profiles at the tumor site. Here, a macrophage-membrane-coated nanoparticle is developed for tumor-targeted chemotherapy delivery with a controlled release profile in response to tumor microenvironment stimuli. Upon fulfilling its mission of tumor homing and RES evasion, the macrophage-membrane coating can be shed via morphological changes driven by extracellular microenvironment stimuli. The nanoparticles discharged from the outer membrane coating show penetration efficiency enhanced by their size advantage and surface modifications. After internalization by the tumor cells, the loaded drug is quickly released from the nanoparticles in response to the endosome pH. The designed macrophage-membrane-coated nanoparticle (cskc-PPiP/PTX@Ma) exhibits an enhanced therapeutic effect inherited from both membrane-derived tumor homing and step-by-step controlled drug release. Thus, the combination of a biomimetic cell membrane and a cascade-responsive polymeric nanoparticle embodies an effective drug delivery system tailored to the tumor microenvironment.