Mingyu He

The induction of proinflammatory T cells by dendritic cell (DC) subtypes is critical for antitumor responses and effective immune checkpoint blockade (ICB) therapy. Here, we show that human CD1c ⁺ CD5 ⁺ DCs are reduced in melanoma-affected lymph nodes, with CD5 expression on DCs correlating with patient survival. Activating CD5 on DCs enhanced T cell priming and improved survival after ICB therapy. CD5 ⁺ DC numbers increased during ICB therapy, and low interleukin-6 (IL-6) concentrations promoted their de novo differentiation. Mechanistically, CD5 expression by DCs was required to generate optimally protective CD5 ^hi T helper and CD8 ⁺ T cells; further, deletion of CD5 from T cells dampened tumor elimination in response to ICB therapy in vivo. Thus, CD5 ⁺ DCs are an essential component of optimal ICB therapy.

Gambogic acid (GA) exhibits a broad spectrum of anticancer activity and low chemotoxicity to normal tissues. However, poor aqueous solubility and sensitivity to hydrolysis make its pharmaceutical applications a challenge. Linear and branched Arg‐based poly(ester urea urethane)s (Arg‐PEUUs), folate (FA)‐conjugated Arg PEUUs (FA‐Arg‐PEUUs), and their self‐assembled nanoparticles (NPs) were designed, synthesized, and studied as the potential GA carriers for cancer treatment. The average diameters of linear or branched Arg‐PEUU/FA‐Arg‐PEUU NPs were 98–267 nm. FA‐Arg‐PEUU NPs adhered onto and were internalized into HeLa and A549 cells, and showed no cytotoxicity. The GA loading efficiency in the NP carriers ranged from 40 to 98%, depending on the feed weight ratio of GA to Arg‐PEUU and the Arg‐PEUU polymer structure (i.e., linear vs. branched). The GA at 2 µg/mL concentration delivered by the FA‐Arg‐PEUU NP carriers had higher cytotoxicity and induced a higher apoptosis percentage against folate receptor (FR)‐overexpressed HeLa or HCT116 than Arg‐PEUU NPs. When compared to the free GA treatment, the GA loaded in the FA‐Arg‐PEUU NP carriers also led to significant loss of the mitochondrial membrane potential in a higher percentage of the cancer cell population and more DNA fragmentation. The GA loaded in FA‐Arg‐PEUU NP carriers at as low as 0.6 µg/mL GA concentration led to lower MMP‐2 and MMP‐9 activity of cancer cells compared to free GA, suggesting that GA‐loaded Arg‐PEUU NPs may have greater potential to reduce cancer cell invasion and metastasis than free GA. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 475–490, 2017.

A new family of cationic hybrid hydrogels from two new positively charged aqueous soluble precursors, glycidyl methacrylate‐chitosan (GMA‐chitosan), and 2‐(acryloyloxy) ethyl trimethylammonium (AETA), was developed via a simple photocrosslinking fabrication method. These hybrid hydrogels have pendant quaternary ammonium functional groups on the AETA segments. The chemical composition of GMA‐chitosan/AETA hybrid hydrogels were characterized by Fourier transform infrared spectroscopy and their mechanical, swelling, and morphological properties were examined as a function of the composition of the hybrids as well as the effect of pH and ionic strength of the surrounding medium. GMA‐chitosan/AETA hybrid hydrogels show a porous network structure with average pore diameter 20–50 μm. The compression moduli of these hybrid hydrogels ranged from 27.24 to 28.94 kPa, which are significantly higher than a pure GMA‐chitosan (17.64 kPa). GMA‐chitosan/AETA hybrid hydrogel shows pH/ionic strength responsive swelling behavior because of the presence of the positive charge pendant groups. These hybrid hydrogels showed a sustained BSA protein release and a significantly lower initial burst release than a pure GMA‐chitosan hydrogel. The two aqueous soluble precursors and the cationic charge characteristics of the resulting GMA‐chitosan/AETA hybrid hydrogels may suggest that this new family of biomaterials may have promising applications as the pH responsive protein drug delivery vehicles. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 3736–3745, 2013