Van‐Sieu Luc

Abstract T lymphocytes play a central role in immunotherapy, utilizing physical interactions to actively inhibit the development of metastases. However, tumor immune privilege and heterogeneity pose challenges by protecting against immune attacks and limiting immune cell infiltration into tumors, particularly in invasive metastatic clusters. Here, a tumor penetrating magnetic particles (TUP) containing the cascade‐responsive cell membrane‐mimetic copolymer (zwitterionic 2‐methacryloyloxyethyl phosphorylcholine‐co‐3‐hydroxypyridin‐4‐one, PH) and cuproptosis molecules (elesclomol‐copper, EsCu) for programming T cell infiltration is developed. The intravenously injected TUP accumulates at the tumor via the charge conversion of PH and hyperthermia effects of TUP. In metastatic clusters, ES and Cu, triggered by intracellular environments and hyperthermia, are readily released. ES and Cu simultaneously induce cuproptosis of cancer cells and stimulate immune responses. This process destroys self‐defense mechanisms and exacerbates cytotoxicity. The therapies facilitate the release of tumor‐associated antigens, including neoantigens and damage‐associated molecular patterns. Following this, the 3‐hydroxypyridin‐4‐one groups on TUP act as antigen reservoirs, transporting autologous tumor‐associated antigens to dendritic cells, thereby inducing prolonged immune activation. TUP acts as an antigen reservoir in copper apoptosis‐mediated lung metastasis, promoting the accumulation of immune cells in metastatic clusters and effectively preventing the progression of metastatic tumors.

Biofouling due to nonspecific proteins or cells on the material surfaces is a major challenge in a range of applications such as biosensors, medical devices, and implants. Even though poly(ethylene glycol) (PEG) has become the most widely used stealth material in medical and pharmaceutical products, the number of reported cases of PEG-triggered rare allergic responses continues to increase in the past decades. Herein, a new type of antifouling material poly(amine oxide) (PAO) has been evaluated as an alternative to overcome nonspecific foulant adsorption and impart comparable biocompatibility. Alkyl-substituted PAO containing diethyl, dibutyl, and dihexyl substituents are prepared, and their solution properties are studied. Photoreactive copolymers containing benzophenone as the photo-cross-linker are prepared by reversible addition-fragmentation chain-transfer polymerization and fully characterized by gel permeation chromatography and dynamic light scattering. Then, these water-soluble polymers are anchored onto a silicon wafer with the aid of UV irradiation. By evaluating the fouling resistance properties of these modified surfaces against various types of foulants, protein adsorption and bacterial attachment assays show that the cross-linked PAO-modified surface can efficiently inhibit biofouling. Furthermore, human blood cell adhesion experiments demonstrate that our PAO polymer could be used as a novel surface modifier for biomedical devices.

The design of novel molecules is imperative for the discovery of potent drugs in the medicinal chemistry field. In this work, new 1,3,5-substituted pyrazoline sulphonamides were synthesised using a two-step process with microwave assistance and evaluated biologically for their antimicrobial, antiproliferative, and anti-inflammatory properties. Most of the sulphonamides bearing 3-OH or 4-Cl groups exhibited significant inhibition of two Gram-positive bacteria, Bacillus subtillis and Staphylococcus aureus, and the yeast Candida albicans. Six compounds showed good activity against the cancer cell lines cervix carcinoma (Hep-2C) and human lung carcinoma (A549) with IC50 in the range 16.03 ± 1.63 to 22.75 ± 0.19 μM and 18.64 ± 1.02 to 20.66 ± 2.09 μM, respectively, and exhibited low toxicity against mammalian Vero cells. In evaluating in vitro anti-inflammatory behaviour, five compounds showed high inhibition of NO production over the standard reference, with low toxicity against murine macrophage cell line RAW 264.7. Further investigation found that two compounds, 1b and 18b, exhibited the highest activity when testing mouse ear oedema. The findings are promising for the discovery of potent new drugs.

Abstract Force‐responsive molecules that produce fluorescent moieties under stress provide a means for stress‐sensing and material damage assessment. In this work, we report a mechanophore based on Diels‐Alder adduct TAD‐An of 4,4′‐(4,4′‐diphenylmethylene)‐bis‐(1,2,4‐triazoline‐3,5‐dione) and initiator‐substituted anthracene that can undergo retro‐Diels‐Alder (rDA) reaction by pulsed ultrasonication and compressive activation in bulk materials. The influence of having C−N versus C−C bonds at the sites of bond scission is elucidated by comparing the relative mechanical strength of TAD‐An to another Diels‐Alder adduct MAL‐An obtained from maleimide and anthracene. The susceptibility to undergo rDa reaction correlates well with bond energy, such that C−N bond containing TAD‐An degrades faster C−C bond containing MAL‐An because C−N bond is weaker than C−C bond. Specifically, the results from polymer degradation kinetics under pulsed ultrasonication shows that polymer containing TAD‐An has a rate constant of 1.59×10 −5 min −1 , while MAL‐An (C−C bond) has a rate constant of 1.40×10 −5 min −1 . Incorporation of TAD‐An in a crosslinked polymer network demonstrates the feasibility to utilize TAD‐An as an alternative force‐responsive probe to visualize mechanical damage where fluorescence can be “turned‐on” due to force‐accelerated retro‐Diels‐Alder reaction.