posted on 2021-12-13, 15:07authored byXiaolong Liang, Min Chen, Pravin Bhattarai, Sadaf Hameed, Yida Tang, Zhifei Dai
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 (Fe3O4@PGL NPs). The amphiphilic PGL easily self-assembled
on the hydrophobic exterior surface of ultrasmall Fe3O4 NPs, resulting in a final ultrasmall Fe3O4@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 Fe3O4@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 Fe3O4@PGL NPs/Fe3O4@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 accelerating
the Fenton reaction in vitro. In our results, the
Fe ions released in vitro directly contributed to
the Fenton reaction, whereas the presence of RAW 264.7 macrophages
further accelerated the ROS generation as observed by the fluorescence
imaging. The significant increase in the ROS during the coincubation
of NPs, endocytosed by HT-29 cells and RAW264.7 cells, further induced
increased cellular toxicity of cancer cells.