Polymers represent a promising therapeutic
platform for extrahepatic
messenger RNA (mRNA) delivery but are hampered by low in vivo efficacy due to polyplex serum instability and inadequate endosomal
escape following systemic administration. Here, we report the rational
design and combinatorial synthesis of zwitterionic phospholipidated
polymers (ZPPs) via cationic polymer postmodification by alkylated
dioxaphospholane oxides to deliver mRNA to spleen and lymph nodes in vivo. This modular postmodification approach readily
produces tunable zwitterionic species for serum resistance and introduces
alkyl chains simultaneously to enhance endosomal escape, thereby transforming
deficient cationic polymers to efficacious zwitterionic mRNA carriers
without the need to elaborately synthesize functional monomers. ZPPs
mediated up to 39 500-fold higher protein expression than their
parent cationic counterparts in vitro and enabled
efficacious mRNA delivery selectively in spleen and lymph nodes following
intravenous administration in vivo. This zwitterionic
phospholipidation methodology provides a versatile and generalizable
postmodification strategy to introduce zwitterions into the side chains
of cationic polymers, extending the utility of cationic polymer families
for precise mRNA delivery and demonstrating substantial potential
for immunotherapeutic applications.
Star polymers have been gaining interest due to their tunable properties. They have been used as effective stabilizers for Pickering emulsions. Herein, star polymers were synthesized via activators regenerated by electron transfer (ARGET) atom transfer radical polymerization (ATRP). Poly(ethylene oxide) (PEO) with terminal α-bromoisobutyrate ATRP functionality was used as a macroinitiator and divinylbenzene as a crosslinker for the arm-first star synthesis. Stars with PEO arms with a molar mass of either 2 or 5 kDa had a relatively low density of grafted chains, i.e., ca. 0.25 chain/nm 2 . The properties of PEO stars adsorbed at oil−water interfaces were investigated using interfacial tension and interfacial rheology. The magnitude of interfacial tensions at oil−water interfaces depends on the nature of the oil phase, being lower at the m-xylene/water interface than at the n-dodecane/water interface. Small differences were observed for stars with different molecular weights of PEO arms. The overall behavior of PEO stars adsorbed at an interface can be considered as an intermediate between a particle and a linear/branched polymer. Obtained results offer an important insight into the interfacial rheology of PEO star polymers in the context of their application as stabilizers for Pickering emulsions.
Kidney transplantation is one of the treatments for end-stage renal disease in lupus patients. The impact of lupus activity on graft survival is a concern. In this study, we aimed to analyze graft survival and factors affecting outcome of kidney transplantation in 45 lupus patients. The graft survival rate was 98, 98, 88, 85 and 78% at 1, 5, 10, 15 and 20 years, respectively. Hypertension, positive penal reactive antibodies against HLA class 2 antigens, retransplant, younger age of lupus nephritis onset, lower postoperative C4 level and the presence of HBsAg and/or anti-HBe antibody showed significantly negative correlation on graft survival by univariate logistic regression. The only factor that is significantly associated with graft failure after adjusting above factors by multiple regression is the presence of HBsAg and/or anti-HBe antibody (p = .0161). Serological markers for activity including C3, C4 and anti-dsDNA antibody before kidney transplantation and recurrent lupus nephritis were not significantly associated with graft failure. In conclusion, in lupus patients underwent kidney transplantation, preoperative serological markers for lupus activity and recurrent lupus nephritis did not affect the graft outcome. However, hepatitis B virus serology might be a single predictor for graft failure in lupus patients.
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