Enhanced delivery of theranostic liposomes through NO-mediated tumor microenvironment remodeling

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.

Automated summary

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.