Journal
NANOSCALE
Volume 14, Issue 20, Pages 7473-7479Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d2nr01175a
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Funding
- National Natural Science Foundation of China [21974104, 22174105, 51873168]
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This study proposes a strategy for the efficient delivery of nanoagents into tumors by regulating the NO-mediated tumor microenvironment. In mouse experiments, quantum dots and liposomes were encapsulated and loaded with L-arginine to continuously generate NO in the tumor, which activated metalloproteinases in the tumor microenvironment, degraded collagen I, and improved the accumulation and therapeutic efficacy of liposomes in the tumor.
Highly efficient delivery of nanoagents to the tumor region remains the primary challenge for cancer nanomedicine. Herein, we propose a NO-mediated tumor microenvironment (TME) remodeling strategy for the high-efficient delivery of nanoagents into tumor. Quantum dots (QDs) with bright fluorescence in the near-infrared IIb (NIR-IIb, 1500-1700 nm) window and high photothermal conversion efficiency were encapsulated into liposomes for the imaging-guided photothermal therapy (PTT) of tumor. The fabrication of PEG and arginine-glycine-aspartate (RGD) peptide on liposomes ensured the prolonged circulation in vivo and active targeting to tumor. Moreover, the loading of a natural NO generator l-arginine in liposomes realized the continuous generation of NO in the acidic TME. By co-localization fluorescence imaging and western blot of tumor tissue, we confirmed that the release of NO activated the expression of metalloproteinases in TME and further degraded Collagen I in the peripheral region of the tumor, thus removing the barrier for the permeation of liposomes. Attributed to the enhanced accumulation of liposomes inside the tumor, NIR IIb imaging-guided PTT was achieved with remarkable therapeutic efficacy.
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