Erythrocyte‐Membrane‐Enveloped Perfluorocarbon as Nanoscale Artificial Red Blood Cells to Relieve Tumor Hypoxia and Enhance Cancer Radiotherapy

TLDR

Tumor hypoxia reduces radiotherapy effectiveness because oxygen is required for radiation‑induced cell damage. The study develops a nanoscale artificial red‑blood‑cell system that encapsulates perfluorocarbon in PLGA and coats it with red‑blood‑cell membrane to deliver oxygen to tumors. The resulting PFC@PLGA‑RBCM nanoparticles load oxygen efficiently, circulate longer, and, due to their nanoscale size, penetrate tumors more effectively than native red blood cells. These nanoparticles relieve tumor hypoxia and markedly improve radiotherapy outcomes, offering a novel nanoscale RBC mimic for oxygen delivery to solid tumors.

Abstract

Hypoxia, a common feature within many types of solid tumors, is known to be closely associated with limited efficacy for cancer therapies, including radiotherapy (RT) in which oxygen is essential to promote radiation-induced cell damage. Here, an artificial nanoscale red-blood-cell system is designed by encapsulating perfluorocarbon (PFC), a commonly used artificial blood substitute, within biocompatible poly(d,l-lactide-co-glycolide) (PLGA), obtaining PFC@PLGA nanoparticles, which are further coated with a red-blood-cell membrane (RBCM). The developed PFC@PLGA-RBCM nanoparticles with the PFC core show rather efficient loading of oxygen, as well as greatly prolonged blood circulation time owing to the coating of RBCM. With significantly improved extravascular diffusion within the tumor mass, owing to their much smaller nanoscale sizes compared to native RBCs with micrometer sizes, PFC@PLGA-RBCM nanoparticles are able to effectively deliver oxygen into tumors after intravenous injection, leading to greatly relieved tumor hypoxia and thus remarkably enhanced treatment efficacy during RT. This work thus presents a unique type of nanoscale RBC mimic for efficient oxygen delivery into solid tumors, favorable for cancer treatment by RT, and potentially other types of therapy as well.