Stimuli-Responsive Phosphate Hydrogel: A Study on Swelling Behavior, Mechanical Properties, and Application in Expansion Microscopy.

Phosphorus-based stimuli-responsive hydrogels have potential in a wide range of applications due to their ionizable phosphorus groups, biocompatibility, and tunable swelling capacity utilizing hydrogel design parameters and external stimuli. In this study, poly(2-methacryloyloxyethyl phosphate) (PMOEP) hydrogels were synthesized via aqueous activators regenerated by electron transfer atomic transfer radical polymerization using ascorbic acid as the reducing agent. Swelling and deswelling behaviors of PMOEP hydrogels were examined in different salt solutions, pH conditions, and temperatures. The degree of swelling in salt solutions followed CaCl2 < MgCl2 < KCl < NaCl with a decrease in swelling rate at higher concentrations until reaching a saturation point. In water, the degree of swelling increased significantly around neutral pH and remained constant at basic pH values. The effects of polymerization conditions, including pH, temperature (30, 40, 50 °C), and MOEP concentration (40, 50, 60% v/v MOEP/H2O), on the hydrogel swelling behavior in various salt solutions were also investigated. PMOEP hydrogels showed a decrease in the degree of swelling as the pH was increased above the native pH of the monomer solution. Scanning electron microscopy and energy-dispersive spectroscopy were utilized to examine the microstructure and chemical composition of the dried hydrogel after salt solution swelling. Cytotoxicity testing using rat bone marrow stem cells confirmed the biocompatibility of the PMOEP hydrogels. A unique feature of this effort was evaluation of these phosphate hydrogels for use in expansion microscopy where a significant twofold enhancement in cellular expansion capacity was showcased utilizing 4T1 mouse breast cancer cells. This comprehensive study provides valuable insights into the stimuli-responsive behavior and expansion characteristics of phosphate hydrogels, highlighting their potential in diverse biomedical applications.

Rational immunosilencing of a promiscuous T-cell epitope in the capsid of an adeno-associated virus.

Owing to the immunogenicity of adeno-associated viruses (AAVs), gene therapies using AAVs face considerable obstacles. Here, by leveraging ex vivo T-cell assays, the prediction of epitope binding to major histocompatibility complex class-II alleles, sequence-conservation analysis in AAV phylogeny and site-directed mutagenesis, we show that the replacement of amino acid residues in a promiscuous and most immunodominant T-cell epitope in the AAV9 capsid with AAV5 sequences abrogates the immune responses of peripheral blood mononuclear cells to the chimaeric vector while preserving its functions, potency, cellular specificity, transduction efficacy and biodistribution. This rational approach to the immunosilencing of capsid epitopes promiscuously binding to T cells may be applied to other AAV vectors and epitope regions.

Mesoporous Silica Nanoparticles: Properties and Strategies for Enhancing Clinical Effect.

Due to the theragnostic potential of mesoporous silica nanoparticles (MSNs), these were extensively investigated as a novel approach to improve clinical outcomes. Boasting an impressive array of formulations and modifications, MSNs demonstrate significant in vivo efficacy when used to identify or treat myriad malignant diseases in preclinical models. As MSNs continue transitioning into clinical trials, a thorough understanding of the characteristics of effective MSNs is necessary. This review highlights recent discoveries and advances in MSN understanding and technology. Specific focus is given to cancer theragnostic approaches using MSNs. Characteristics of MSNs such as size, shape, and surface properties are discussed in relation to effective nanomedicine practice and projected clinical efficacy. Additionally, tumor-targeting options used with MSNs are presented with extensive discussion on active-targeting molecules. Methods for decreasing MSN toxicity, improving site-specific delivery, and controlling release of loaded molecules are further explained. Challenges facing the field and translation to clinical environments are presented alongside potential avenues for continuing investigations.