2D graphene oxide-L-arginine-soybean lecithin nanogenerator for synergistic photothermal and NO gas therapy

Nitric oxide(NO) gas therapy has been regarded as a promising strategy for cancer treatment. However,its therapeutic efficiency is still unsatisfying due to the limitations of monotherapy. Previous preclinical and clinical studies have shown that combination therapy could significantly enhance therapeutic efficiency. Herein, a graphene oxide(GO)-L-arginine(L-Arg, a natural NO donor) hybrid nanogenerator is developed followed by surface functionalization of soybean lecithin(SL) for synergistic enhancement of cancer treatment through photothermal and gas therapy. The resultant GO-Arg-SL nanogenerator not only exhibited good biocompatibility and excellent endocytosis ability, but also exhibited excellent photothermal conversion capability and high sensitivity to release NO within tumor microenvironment via inducible NO synthase(i NOS) catalyzation. Moreover, the produced hyperthermia and intracellular NO could synergistically kill cancer cells both in vitro and in vivo. More importantly, this nanogenerator can efficiently eliminate tumor while inhibiting the tumor recurrence because of the immunogenic cell death(ICD) elicited by NIR laser-triggered hyperthermia and the immune response activation by massive NO generation. We envision that the GO-Arg-SL nanogenerator could provide a potential strategy for synergistic photothermal and gas therapy.

Synthesis of NaYF_(4):20% Yb^(3+),2% Er^(3+),2% Ce^(3+)@NaYF_(4) nanorods and their size dependent uptake efficiency under flow condition

Lanthanide doped fluorescent nanoparticles have gained considerable attention in biomedical applications.However,the low uptake efficiency of nanoparticles by cells has limited their applications.In this work,we demonstrate how the uptake efficiency is affected by the size of nanoparticles under flow conditions.Using the same size NaYF_(4):20%Yb^(3+),2%Er^(3+),2%Ce^(3+)(the contents of rare earths elements are in molar fraction)nanoparticles as core,NaYF_(4):20%Yb^(3+),2%Er^(3+),2%Ce^(3+)@NaYF_(4) core-shell structured nanorods(NRs)with different sizes of 60-224 nm were synthesized by thermal decomposition and hot injection method.Under excitation at 980 nm,a strong upconversion green emission(541 nm,^(2)H_(11/2)→^(4) I_(15/2) of Er^(3+))is observed for all samples.The emission intensity for each size nanorod was calibrated and is found to depend on the width of NRs.Under flow conditions,the nanorods with 96 nm show a maximum uptake efficiency by endothelial cells.This work demonstrates the importance of optimizing the size for improving the uptake efficiency of lanthanide-doped nanoparticles.