Hydrogel-Mediated Jamming of Exosome Communications That Counter Tumor Adaption in the Tumor Immune Microenvironment.

Hypoxia, a common occurrence within solid tumors, can stimulate the dissemination of deceptive tumor exosomes, which function as communicative bridges and orchestrate the recruitment of various supportive cell types for enhanced tumor adaptability in a tumor immune microenvironment. Current nanotechnology provides us intelligent strategies to combat the hypoxic tumor microenvironment. However, once exposed to external stimuli, such as chemotherapy, tumor cells simultaneously release malignant signals to develop tumor migration and immunosuppression, posing challenges to clinical practice. Taking advantage of the membrane-targeting therapeutic strategy, the application of a self-assembled short peptide (PepABS-py), affording hydrogels on tumor cell surfaces, can block exosome dissemination with fiber-like nanostructures and effectively limit the systemic adverse effects of traditional therapeutics. Moreover, PepABS-py can attenuate the hypoxic tumor microenvironment in vivo by carrying an inhibitor of the hypoxic tumor-overexpressed CA IX enzyme, where hypoxia is also a crucial regulator to induce tumor exosomes and mediate intercellular communications within the immune system. Herein, its application on jamming exosome communications can target the T cell-related signaling pathway by regulating microRNAs in exosome cargoes and ultimately enhances CD8+ T cell infiltration and alleviates inflammatory monocytes at metastasis sites. Collectively, with the capability of blocking exosome dissemination, PepABS-py can be applied as a promising tumor membrane-targeting therapeutic tool to counter tumor adaption within an immune microenvironment and further advance traditional chemotherapy.

Injectable Hydrogel Mucosal Vaccine Elicits Protective Immunity against Respiratory Viruses.

Intranasal vaccines, eliciting mucosal immune responses, can prevent early invasion, replication, and transmission of pathogens in the respiratory tract. However, the effective delivery of antigens through the nasal barrier and boosting of a robust systematic and mucosal immune remain challenges in intranasal vaccine development. Here, we describe an intranasally administered self-healing hydrogel vaccine with a reversible strain-dependent sol-gel transition by precisely modulating the self-assembly processes between the natural drug rhein and aluminum ions. The highly bioadhesive hydrogel vaccine enhances antigen stability and prolongs residence time in the nasal cavity and lungs by confining the antigen to the surface of the nasal mucosa, acting as a "mucosal mask". The hydrogel also stimulates superior immunoenhancing properties, including antigen internalization, cross-presentation, and dendritic cell maturation. Furthermore, the formulation recruits immunocytes to the nasal mucosa and nasal-associated lymphoid tissue (NALT) while enhancing antigen-specific humoral, cellular, and mucosal immune responses. Our findings present a promising strategy for preparing intranasal vaccines for infectious diseases or cancer.

Advances in versatile anti-swelling polymer hydrogels.

Swelling is ubiquitous for traditional as-prepared hydrogels, but is unfavorable in many situations, especially biomedical applications, such as tissue engineering, internal wound closure, soft actuating and bioelectronics, and so forth. As the swelling of a hydrogel usually leads to a volume expansion, which not only deteriorates the mechanical property of the hydrogel but can bring about undesirable oppression on the surrounding tissues when applied in vivo. In contrast, anti-swelling hydrogels hardly alter their volume when applied in aqueous environment, therefore reserving the original mechanical performance and size-stability and facilitating their potential application. In the past decade, with the development of advanced hydrogels, quite a number of anti-swelling hydrogels with versatile functions have been developed by researchers to meet the practical applications well, through integrating anti-swelling property with certain performance or functionality, such as high strength, self-healing, injectability, adhesiveness, antiseptics, etc. However, there has not been a general summary with regard to these hydrogels. To promote the construction of anti-swelling hydrogels with desirable functionalities in the future, this review generalizes and analyzes the tactics employed so far in the design and manufacture of anti-swelling hydrogels, starting from the viewpoint of classical swelling theories. The review will provide a relatively comprehensive understanding of anti-swelling hydrogels and clues to researchers interested in this kind of materials to develop more advanced ones suitable for practical application.

Metal ions modulation of the self-assembly of short peptide conjugated nonsteroidal anti-inflammatory drugs (NSAIDs).

Metal ions are essential components that help maintain the processes of normal life, and they can be used to fabricate self-assembled building blocks for peptide derivatives, proteins and nucleic acids. Here, we have developed a novel strategy to construct supramolecular hydrogels modulated using metal cations. Upon introducing a variety of metal ions into aqueous solutions of a gelator (naproxen-FF), including a nonsteroidal anti-inflammatory drug (NSAID) and dipeptide, we obtain stable hydrogels under neutral or alkaline conditions. It is found that these hydrogels with three-dimensional nanofiber networks exhibit excellent mechanical properties and thixotropy, as well as superb responsivity to multiple metal ions. Due to the significance of potassium ions in biological processes, the K-triggered hydrogel has been chosen as a model, and its self-assembly mechanism has been explored via various spectral analysis processes. In addition, the self-assembly performances of peptides are significantly affected by the chemical structures of the gelator molecules. This work provides deep insight into the aggregation mechanism of dipeptide-conjugating drug molecules through introducing a variety of metal ions, laying the foundation for further biological applications.

New power of self-assembling carbonic anhydrase inhibitor: Short peptide-constructed nanofibers inspire hypoxic cancer therapy.

Carbonic anhydrase (CA) IX overexpresses exclusively on cell membranes of hypoxic tumors, regulating the acidic tumor microenvironment. Small molecules of CA inhibitor modified with short peptide successfully achieve CA IX-targeted self-assembly that localizes CA inhibitors on hypoxic cancer cell surfaces and enhances their inhibition efficacy and selectivity. CA IX-related endocytosis also promotes selective intracellular uptake of these nanofibers under hypoxia, in which nanofiber structures increase in size with decreasing pH. This effect subsequently causes intracellular acid vesicle damage and blocks protective autophagy. The versatility of tunable nanostructures responding to cell milieu impressively provokes selective toxicities and provides strategic therapy for hypoxic tumors. Moreover, in vivo tests demonstrate considerable antimetastatic and antiangiogenesis effects in breast tumors, and particularly remarkable enhancement of antitumor efficacy in doxorubicin administration. With its biocompatible components and distinctive hypoxia therapies, this nanomaterial advances current chemotherapy, providing a new direction for hypoxic cancer therapy.