Age-dependent changes in phagocytic activity: in vivo response of mouse pulmonary antigen presenting cells to direct lung delivery of charged PEGDA nanoparticles.

BACKGROUND: Current needle-based vaccination for respiratory viruses is ineffective at producing sufficient, long-lasting local immunity in the elderly. Direct pulmonary delivery to the resident local pulmonary immune cells can create long-term mucosal responses. However, criteria for drug vehicle design rules that can overcome age-specific changes in immune cell functions have yet to be established. RESULTS: Here, in vivo charge-based nanoparticle (NP) uptake was compared in mice of two age groups (2- and 16-months) within the four notable pulmonary antigen presenting cell (APC) populations: alveolar macrophages (AM), interstitial macrophages (IM), CD103+ dendritic cells (DCs), and CD11b+ DCs. Both macrophage populations exhibited preferential uptake of anionic nanoparticles but showed inverse rates of phagocytosis between the AM and IM populations across age. DC populations demonstrated preferential uptake of cationic nanoparticles, which remarkably did not significantly change in the aged group. Further characterization of cell phenotypes post-NP internalization demonstrated unique surface marker expression and activation levels for each APC population, showcasing heightened DC inflammatory response to NP delivery in the aged group. CONCLUSION: The age of mice demonstrated significant preferences in the charge-based NP uptake in APCs that differed greatly between macrophages and DCs. Carefully balance of the targeting and activation of specific types of pulmonary APCs will be critical to produce efficient, age-based vaccines for the growing elderly population.

Bridging the gender gap in autoimmunity with T-cell-targeted biomaterials.

Autoimmune diseases are caused by malfunctions of the immune system and generally impact women at twice the frequency of men. Many of the most serious autoimmune diseases are accompanied by a dysregulation of T-cell phenotype, both regarding the ratio of CD4+ to CD8+ T-cells and proinflammatory versus regulatory phenotypes. Biomaterials, in the form of particles and hydrogels, have shown promise in ameliorating this dysregulation both in vivo and ex vivo. In this review, we explore the role of T-cells in autoimmune diseases, particularly those with high incidence rates in women, and evaluate the promise and efficacy of innovative biomaterial-based approaches for targeting T-cells.

Single and Multiple Stimuli-Responsive Polymer Particles for Controlled Drug Delivery.

Polymers that can change their properties in response to an external or internal stimulus have become an interesting platform for drug delivery systems. Polymeric nanoparticles can be used to decrease the toxicity of drugs, improve the circulation of hydrophobic drugs, and increase a drug's efficacy. Furthermore, polymers that are sensitive to specific stimuli can be used to achieve controlled release of drugs into specific areas of the body. This review discusses the different stimuli that can be used for controlled drug delivery based on internal and external stimuli. Internal stimuli have been defined as events that evoke changes in different characteristics, inside the body, such as changes in pH, redox potential, and temperature. External stimuli have been defined as the use of an external source such as light and ultrasound to implement such changes. Special attention has been paid to the particular chemical structures that need to be incorporated into polymers to achieve the desired stimuli response. A current trend in this field is the incorporation of several stimuli in a single polymer to achieve higher specificity. Therefore, to access the most recent advances in stimuli-responsive polymers, the focus of this review is to combine several stimuli. The combination of different stimuli is discussed along with the chemical structures that can produce it.

Novel Silver-Platinum Nanoparticles for Anticancer and Antimicrobial Applications.

BACKGROUND: Cancer is a disease with an enormous worldwide impact. One of the fatal complications in cancer patients are bacterial opportunistic infections. The use of chemotherapeutic drugs made cancer remission more frequent and prolonged patient survival, but, increased the risk of infections. PURPOSE: Address the current problem with growing pandemic cancer and considering high risks of complications with bacterial infections, the present study synthesized novel dendritic assembly of silver (Ag)-platinum (Pt) nanoparticles. METHODS: Nanoparticles were characterized by TEM analysis, and the composition was confirmed by EDX. Bacterial studies were performed for Gram-positive Staphylococcus aureus, Gram-negative Pseudomonas aeruginosa and Gram-negative multi-drug resistant Escherichia coli. Cell experiments were performed with two different cancer cell lines, glioblastoma and melanoma to determine anticancer activity. Finally, cytotoxicity with fibroblast was tested. RESULTS: The TEM analysis of silver-platinum (AgPt) nanoparticles showed dendrimer shape nanoparticles with a mean size of 42 ± 11nm. Elemental composition was analyzed by EDX, confirming the presence of both Ag and Pt metals. The synthesized nanoparticles significantly inhibited the growth of medically important pathogenic, Gram-positive Staphylococcus aureus, Gram-negative Pseudomonas aeruginosa and Gram-negative multi-drug resistant Escherichia coli. Bactericidal effect of AgPt nanoparticles had greater effectiveness than silver nanoparticles. MTS assay revealed a selective and dose-dependent anticancer activity of AgPt nanoparticles over cancer cell lines glioblastoma and melanoma in the 10-250 µg/mL concentration range. Cytotoxicity experiments with fibroblast cells showed no side effects of nanoparticles against healthy cells at a range of concentrations from 10-50 µg/mL. CONCLUSION: The newly synthesized AgPt nanoparticles have a promising future as a potent anticancer agent with antibacterial properties.