Oligomerized or polymerized siRNAs with higher molecular weight and anionic charges could form stable and condensed nanoparticle structures with cationic polymers, resulting in enhanced stability and efficient delivery.

The most important problem in current siRNA delivery systems is their inability to form condensed nanoparticles with cationic lipids or polymers. This situation may be because of the low charge density and molecular weight of short double‐stranded siRNAs compared to plasmid DNA, which can form a very stable and condensed nanoparticle structure with cationic molecules.

We designed tGC nanoparticles encapsulated with poly-siRNA targeting TNF-α. It was hypothesized that these nanoparticles may be localized at the arthritic joint sites followed by rapid macrophage uptake and release of free siRNAs by degradation of disulfide linkages, leading to knockdown of target mRNA and the treatment of RA

As previously reported for red blood cell membranes and positively charged polystyrene particles, the production of a nanosystem presenting a positively charged core encapsulated within a cell membrane is hampered by the presence of two opposite charges, the positive from the particles and the negative from the cell membranes

A study of the parameters influencing the production of PSi@cytoplasmic membranes was conducted.

In this work, we adjust PLGA‐b‐PDMA structure and incorporate PEG segments to cNPs made of PLGA‐b‐PDMA to form various cNPs with different charge density. As a result of PEGylation, the surface charge of the nanoparticles and, in turn, their toxicity to cells and rats, were reduced. Therefore, the presence of surface PEG chains efficiently avoids the insurgence of obvious systemic side‐effects, which may greatly increase the translational potential of cNPs. Although PEGylation also affected the DNA binding affinity, the cNPs retained the ability to treat inflamed joints in CIA rats due to their enhanced accumulation and persistence time into inflamed joints.

Relatively to the homoshell cNPs, introduction of PEG segments translates into a lower DNA binding efficacy while preserving ability to hamper joint inflammation. Moreover, they show a greater accumulation and longer retention at the inflamed joints, allowing a lower administration frequency. In conclusion, this work shows that the therapeutic index of cationic materials can be tuned by introducing surface neutral moieties.

The library includes cNPs with a homoshell from poly(lactic‐co‐glycolic acid)‐block‐poly(2‐(dimethylamino)ethyl methacrylate) (PLGA‐b‐PDMA) block copolymers and cNPs with a mixed shell of poly(ethylene glycol) (PEG) and PDMA by coself‐assembling PLGA‐b‐PDMA and PLGA‐b‐PEG block copolymers.

Platelet microparticles were proinflammatory, eliciting cytokine responses from synovial fibroblasts via interleukin-1. Consistent with these findings, depletion of platelets attenuated murine inflammatory arthritis. Using both pharmacologic and genetic approaches, we identified the collagen receptor glycoprotein VI as a key trigger for platelet microparticle generation in arthritis pathophysiology. Thus, these findings demonstrate a previously unappreciated role for platelets and their activation-induced microparticles in inflammatory joint diseases.

molecular forces that mediate ligand-receptor binding (e.g. hydrogen bonds and electrostatic interactions) only extend over ~0.3–0.5 nm [2, 3] and cannot provide a long-distance magnetic pull to a site of therapeutic need. Instead, ligand-targeting can improve delivery by increasing the likelihood that a nanoparticle is retained by a target cell or tissue it happens to contact.