Nanomedicines for reversing immunosuppressive microenvironment of hepatocellular carcinoma.

Although immunotherapeutic strategies such as immune checkpoint inhibitors (ICIs) have gained promising advances, their limited efficacy and significant toxicity remain great challenges for hepatocellular carcinoma (HCC) immunotherapy. The tumor immunosuppressive microenvironment (TIME) with insufficient T-cell infiltration and low immunogenicity accounts for most HCC patients' poor response to ICIs. Worse still, the current immunotherapeutics without precise delivery may elicit enormous autoimmune side effects and systemic toxicity in the clinic. With a better understanding of the TIME in HCC, nanomedicines have emerged as an efficient strategy to achieve remodeling of the TIME and superadditive antitumor effects via targeted delivery of immunotherapeutics or multimodal synergistic therapy. Based on the typical characteristics of the TIME in HCC, this review summarizes the recent advancements in nanomedicine-based strategies for TIME-reversing HCC treatment. Additionally, perspectives on the awaiting challenges and opportunities of nanomedicines in modulating the TIME of HCC are presented. Acquisition of knowledge of nanomedicine-mediated TIME reversal will provide researchers with a better opportunity for clinical translation of HCC immunotherapy.

Natural Products for the Immunotherapy of Glioma.

Glioma immunotherapy has attracted increasing attention since the immune system plays a vital role in suppressing tumor growth. Immunotherapy strategies are already being tested in clinical trials, such as immune checkpoint inhibitors (ICIs), vaccines, chimeric antigen receptor T-cell (CAR-T cell) therapy, and virus therapy. However, the clinical application of these immunotherapies is limited due to their tremendous side effects and slight efficacy caused by glioma heterogeneity, antigen escape, and the presence of glioma immunosuppressive microenvironment (GIME). Natural products have emerged as a promising and safe strategy for glioma therapy since most of them possess excellent antitumor effects and immunoregulatory properties by reversing GIME. This review summarizes the status of current immunotherapy strategies for glioma, including their obstacles. Then we discuss the recent advancement of natural products for glioma immunotherapy. Additionally, perspectives on the challenges and opportunities of natural compounds for modulating the glioma microenvironment are also illustrated.

Preparation, characterisation and comparison of glabridin-loaded hydrogel-forming microneedles by chemical and physical cross-linking.

Poly(vinyl alcohol) (PVA) and carbomer were used as the hydrogel system to fabricate glabridin-loaded hydrogel-forming microneedles (HFMNs) by chemical cross-linking (CCMNs) and physical cross-linking (PCMNs). The properties and drug permeation effects of glabridin-loaded HFMNs with different methods were compared. They both owned excellent shapes, mechanical and insertion properties. PCMNs showed collapsed shapes during swelling due to the low cross-linking rate and high porosity, which probably results in resealing of skin pores during transdermal drug delivery. However, CCMNs could rapidly swell within 2 h with slightly bending. The infrared spectra indicate that CCMNs and PCMNs might form the hydrogel network by generating hydrogen and covalent bonds, respectively. The in vitro release studies showed that cumulative permeation amount within 24 h (1654 µg/cm2) of CCMNs significantly higher than that (372 µg/cm2) achieved by PCMNs and that (118 µg/cm2) achieved by glabridin-loaded gel. The skin barrier recovery test suggests the desirable security of both microneedles (MNs), notwithstanding the presence of mild erythema in the mouse skin applied CCMNs. These results indicate that CCMNs were more desirable for glabridin delivery using PVA and carbomer as a skeleton of the hydrogel network.