Cell Membrane-Camouflaged Nanocarriers with Biomimetic Deformability of Erythrocytes for Ultralong Circulation and Enhanced Cancer Therapy

Abstract

Despite considerable advancements in cell membrane-camouflaged nanocarriers to leverage natural cell functions, artificial nanocarriers that can accurately mimic both the biological and physical properties of cells are urgently needed. Herein, inspired by the important effect of the stiffness and deformability of natural red blood cells (RBCs) on their life span and flowing through narrow vessels, we report the construction of RBC membrane-camouflaged nanocarriers that can mimic RBCs at different life stages and study how the deformability of RBC-derived nanocarriers affects their biological behaviors. RBC membrane-coated elastic poly­(ethylene glycol) diacrylate hydrogel nanoparticles (RBC-ENPs) simulating dynamic RBCs exhibited high immunocompatibility with minimum immunoglobulin adsorption in the surface protein corona, resulting in reduced opsonization in macrophages and ultralong circulation. Furthermore, RBC-ENPs can deform like RBCs and achieve excellent diffusion in tumor extracellular matrix, leading to improved multicellular spheroid penetration and tumor tissue accumulation. In mouse cancer models, doxorubicin-loaded RBC-ENPs demonstrated superior antitumor efficacy to the first-line chemotherapeutic drug PEGylated doxorubicin liposomes. Our work highlights that tuning the physical properties of cell membrane-derived nanocarriers may offer an alternative approach for the bionic design of nanomedicines in the future.

Harnessing Protein Corona for Biomimetic Nanomedicine Design

“…Yunqiu Miao et al developed a novel NPs system whose surface was decorated with natural RBC membranes [ 50 ]. This RBC-mimic system was constructed based on RBC membranes and poly (ethylene glycol) diacrylate (PEGDA) hydrogel nanoparticles, and due to the RBC membrane, this system exhibited many gorgeous properties, including evading the immune system efficiently, penetrating narrow tissue extracellular space of tumors and accumulating in diseased tissues ( Figure 4 A).…”

“…( A ) The RBC-mimic system (RBC-ENPs) was constructed based on the RBC membrane and poly (ethylene glycol) diacrylate (PEGDA) NPs. The RBC cell membrane decoration endowed this system with the ability of immune escape by controlling the composition of the protein corona and deformation for better tumor penetration [ 50 ]. Copyright 2022, American Chemical Society.…”

“…The biomimetic approach aims to mimic natural biological mechanisms and transfer specific natural functionalities to synthetic nanoparticles to achieve therapeutic outcomes or avoid the adverse effects of current synthetic nanomedicine [ 49 ]. For example, the NPs decorated with cell membranes from different kinds of cells like erythrocytes (red blood cell [RBC]) can superiorly reduce undesired immune responses, evade elimination by macrophages, and bypass systemic clearance [ 50 ]. These NPs with RBC cell membranes show long circulation time and gorgeous therapeutic efficacy [ 51 ].…”

Nanomaterials: A powerful tool for tumor immunotherapy

“…The biconcave morphology of erythrocytes gives them excellent deformability and allows for smooth passage through capillaries of several microns. Importantly, erythrocytes are considered an effective bionic drug carrier due to their long circulation time and easy availability in the body ( 114 ).…”

Lipid-Based Nanocarrier Systems for Drug Delivery: Advances and Applications

“…In vivo results showed that doxorubicin-loaded RBC-ENPs exhibited superior antitumor efficacy to the first-line chemotherapeutic drug PEGylated doxorubicin liposomes. 102 These biomembrane-camouflaged nanocarriers exhibit superior efficacy and high safety for disease treatment, which stands for a promising direction of nanocarriers.…”