γδT cells have emerged as a promising target in tumor therapy, prompting the development of novel strategies to activate these cells directly within the tumor microenvironment. In this study, we engineered uniformly sized spherical garlic-derived nanoparticles (GNPs) to stimulate tumor-infiltrating γδT cells. Through intratumoral injection of GNPs, we demonstrated their ability to directly activate γδT cells, leading to potent antitumor effects. This approach resulted in significant inhibition of various subcutaneous tumors in mice. Additionally, under computed tomography (CT) guidance, intratumoral injection of GNPs effectively suppressed the growth of orthotopic liver cancer in New Zealand white rabbits. Mechanistic studies revealed that GNPs robustly activated γδT cells, promoting an inflammatory microenvironment within tumors. Our approach of using garlic-derived nanoparticles offers the advantages of simplicity in preparation and high yield, presenting a promising avenue for tumor therapy with potential for clinical translation.

Uterine infertility is a major global issue causing substantial physical and psychological hardship for individuals struggling to conceive, while endometrium injury is one of the crucial factors causing infertility. Here, we demonstrate that platelet-derived extracellular vesicles (PEVs) have excellent regenerative ability in treating endometrial injuries, facilitating endometrium regeneration and resulting in a highly efficient live birth rate in the endometrium-injured murine model. We further investigated the underlying mechanisms by which PEVs affect the endometrium, showing their ability to promote neovascularization and suppress fibrosis. More importantly, the regenerative endometrium is more receptive to embrace the embryo, which can sustain the normal pregnancy. Our finding serves as a foundational basis for advancing the clinical translation of platelet-rich plasma (PRP) and PEVs therapies for endometrial regeneration.

Despite immune checkpoint blockade (ICB) therapy has transformed cancer treatment, only 20.2% of these patients achieved a response. Understanding resistance mechanisms to ICB is important for the treatment of a wider population. In this work, we occasionally found that the silica nanoparticles (SiO₂ NPs) accumulated in the liver can induce resistance to following ICB therapy to a subcutaneous tumor in mice. By analysis of T cells frequency, we uncovered that SiO₂ NPs in the liver resulted in a siphoning of T cells from circulation to the liver by produced chemokines. In addition, liver immunosuppressive cells further inhibit the function and induce apoptosis of recruited T cells, leading to a systemic loss and reduced tumor infiltration of T cells, which contributes to poor responses to ICB therapy. However, such effect is not observed in poly(lactic-co-glycolic acid) (PLGA) NPs treated mice under the same conditions, likely due to their much lower immunogenicity in perturbing the liver immune microenvironment, indicating that cancer is not a local disease but an ecosystem that is linked to the distal environment. We further provide a new mechanism insight into ICB resistance induced by liver accumulation of nanoparticles.

The enhanced permeability retention (EPR) effect based nanomedicine has been widely used for tumor targeting during the past decades. Here we unexpectedly observed the similar "EPR effect" at the site of injury. We found that the temporary dilated and leaky blood vessels caused by the potent vasodilator histamine in response to injury allowed the injected nanoparticles to pass through the vasculature and reached the injured tissue. Our finding shows the potential underline mechanism of "EPR effect" at the injured site. By loading with antibiotics, we further demonstrated a new strategy for prevention of infection at the site of injury.