Complementing Cancer Photodynamic Therapy with Ferroptosis through Iron Oxide Loaded Porphyrin-Grafted Lipid Nanoparticles

作者：Xiaolong Liang, Min Chen, Pravin Bhattarai, Sadaf Hameed, Yida Tang, Zhifei Dai · 发表于：ACS Nano · 年份：2021 · DOI：10.1021/acsnano.1c08108 · 被引用次数：153 · 研究领域：Nanoplatforms for cancer theranostics、Extracellular vesicles in disease、Nanoparticle-Based Drug Delivery

Nanomaterials that combine multimodality imaging and therapeutic functions within a single nanoplatform have drawn extensive attention for molecular medicines and biological applications. Herein, we report a theranostic nanoplatform based on a relatively smaller (<20 nm) iron oxide loaded porphyrin-grafted lipid nanoparticles (Fe 3 O 4 @PGL NPs). The amphiphilic PGL easily self-assembled on the hydrophobic exterior surface of ultrasmall Fe 3 O 4 NPs, resulting in a final ultrasmall Fe 3 O 4 @PGL NPs with diameter of ∼10 nm. The excellent self-assembling nature of the as-synthesized PGL NPs facilitated a higher loading of porphyrins, showed a negligible dark toxicity, and demonstrated an excellent photodynamic effect against HT-29 cancer cells in vitro . The in vivo experimental results further confirmed that Fe 3 O 4 @PGL NPs were ideally qualified for both the fluorescence and magnetic resonance (MR) imaging guided nanoplatforms to track the biodistribution and therapeutic responses of NPs as well as to simultaneously trigger the generation of highly cytotoxic reactive oxygen species (ROS) necessary for excellent photodynamic therapy (PDT). After recording convincing therapeutic responses, we further evaluated the ability of Fe 3 O 4 @PGL NPs/Fe 3 O 4 @Lipid NPs for ferroptosis therapy (FT) via tumor microenvironment (TME) modulation for improved anticancer activity. We hypothesized that tumor-associated macrophages (TAMs) could significantly improve the efficacy of FT by ac...