Issue 32, 2021

A co-delivery nanoplatform for a lignan-derived compound and perfluorocarbon tuning IL-25 secretion and the oxygen level in tumor microenvironments for meliorative tumor radiotherapy

Abstract

A hypoxic environment in tumors hampers the therapeutic efficacy of radiotherapy. Moreover, radiotherapy, a localized treatment technique, can barely control tumor metastases. Herein, poly(lactic-co-glycolic acid) was used to encapsulate perfluorocarbon (PFC) for increasing the oxygen level and a lignan-derived compound (Q1) for enhancing IL-25 secretion from fibroblasts, thereby boosting the radiotherapeutic effect on local and distant tumors. The prepared co-delivery nanoplatform, PFC-Q1@PLGA, has a nano-scale size of around 160 nm and a negative zeta potential (about −13 mV). PFC-Q1@PLGA treatment leads to an arrest of the G2 phase (4n) in the cell cycle and reduces the mitochondria membrane potential. A high expression level of IL-25 in fibroblasts is detected after the cells are treated with PFC-Q1@PLGA, which increases the late apoptosis percentage of 4T1 cells after treatment with IL-25-containing conditional medium from fibroblasts. The oxygen level in tumors is significantly promoted to about 52.3% after injection of oxygen-saturated PFC-Q1@PLGA (O2), which is confirmed from the functional magnetic resonance images of the tumor site in mice. The in vivo study demonstrates that the injection of PFC-Q1@PLGA (O2) into local tumors significantly enhances the radiotherapeutic effect on local tumors and also inhibits the growth of remote tumors by an enhanced abscopal effect. This study presents a novel radiotherapy strategy to enable synergistic whole-body therapeutic responses after localized treatment with PFC-Q1@PLGA (O2).

Graphical abstract: A co-delivery nanoplatform for a lignan-derived compound and perfluorocarbon tuning IL-25 secretion and the oxygen level in tumor microenvironments for meliorative tumor radiotherapy

Supplementary files

Article information

Article type
Paper
Submitted
09 Jūn. 2021
Accepted
13 Jūl. 2021
First published
13 Jūl. 2021

Nanoscale, 2021,13, 13681-13692

A co-delivery nanoplatform for a lignan-derived compound and perfluorocarbon tuning IL-25 secretion and the oxygen level in tumor microenvironments for meliorative tumor radiotherapy

Z. Duan, Q. Luo, L. Gu, X. Li, H. Zhu, Z. Gu, Q. Gong, H. Zhang and K. Luo, Nanoscale, 2021, 13, 13681 DOI: 10.1039/D1NR03738B

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