Synergistic enhancement of ultrasound therapy for tumors using hypoxia-activated 6-diazo-5-oxo-L-norleucine(DON)prodrug nanoparticles

Ultrasound(US)has been applied in clinical practice for its non-invasive and high selectivity.However,it is difficult to achieve a satisfactory anti-tumor effect with US alone.Meanwhile,the use of US therapy alone can exacerbate tumor hypoxia.In this study,we prepared hypoxia-activated 6-diazo-5-oxo-L-norleucine(DON)prodrug nanoparticles(HDON-NPs)to improve US therapeutic effects.In an H22 murine liver cancer model,US therapy selectively disrupted tumor blood vessels,leading to increased tumor hypoxia and a 1.67-fold increase in the expression of nitroreductase(NTR).The combination therapy of US and HDON-NPs demonstrated a synergistic effect,resulting in a tumor suppression rate(TSR)of 90.2%±6.4%,which was 5.93-fold higher than that of US therapy alone.The combined treatment selectively blocked the glutamine metabolism of the tumor cells while simultaneously activating the T cells in the tumor microenvironment,thereby exerting a robust anti-tumor effect.

A tumor-targeting nano-adjuvant for in situ vaccine based on ultrasound therapy

Ultrasound-generated antigens combined with TLR7/8 agonists as adjuvants have demonstrated significant anti-tumor efficacy as an in-situ vaccine.However,the use of TLR7/8 agonists can cause severe inflammatory responses.In this study,we present a novel tumor-targeting nano-adjuvant termed aPDL1-PLG/R848 NPs,which are composed of aPDL1 antibody,Fc-III-4C peptide linker(Fc-linker)and poly(L-glutamic acid)-grafted-R848.Under ultrasound irradiation,antigen-presenting cells activate immune mechanisms in vivo under dual stimulation of in situ antigens and immune adjuvants.The strategy inhibits primary tumor growth and induces a strong antigen-specific immune memory effect to prevent tumor recurrence in vivo.This work offers a safe and potent platform for an in situ cancer vaccine based on ultrasound therapy.

Multifunctional magnetic nanoparticles for magnetic resonance image-guided photothermal therapy for cancer

Key advances in multifunctional magnetic nanoparticles （MNPs） for magnetic resonance （MR） image-guided pho- tothermal therapy of cancer are reviewed. We briefly outline the design and fabrication of such multifunctional MNPs. Bimodal image-guided photothermal therapies （MR/fluorescence and MR/ultrasound） are also discussed.