中文摘要：研究开发了一类新的瞬态温敏缩醛聚合物，该聚合物在室温以下具备相变温度，在内核pH值下能够通过缩醛水解逐渐转化成全溶性聚合物。RAFT聚合反应能够产生嵌段共聚核物，这种聚合物可以自行组配成胶束状纳米颗粒，并能有效包被两性霉素B（AmpB）。重要的是，这种纳米胶囊能够显著降低AmpB的细胞毒性作用，维持其激活TLR的特性。通过小鼠体外试验表明，装载AmpB的纳米颗粒能够作为呼吸道合包病毒（RSV）疫苗的佐剂进行应用。
外文摘要：The quest for new potent and safe adjuvants with which to skew and boost the immune response of vaccines against intracellular pathogens and cancer has led to the discovery of a series of small molecules that can activate Toll-like receptors (TLRs). Whereas many small molecule TLR agonists cope with a problematic safety profile, amphotericin B (AmpB), a Food and Drug Administration approved antifungal drug, has recently been discovered to possess TLR-triggering activity. However, its poor aqueous solubility and cytotoxicity at elevated concentrations currently hampers its development as a vaccine adjuvant. We present a new class of transiently thermoresponsive polymers that, in their native state, have a phase-transition temperature below room temperature but gradually transform into fully soluble polymers through acetal hydrolysis at endosomal pH values. RAFT polymerization afforded well-defined block copolymers that self-assemble into micellar nanoparticles and efficiently encapsulate AmpB. Importantly, nanoencapsulation strongly reduced the cytotoxic effect of AmpB but maintained its TLR-triggering capacity. Studies in mice showed that AmpB-loaded nanoparticles can adjuvant an RSV vaccine candidate with almost equal potency as a highly immunogenic oil-in-water benchmark adjuvant.
外文关键词：RESPIRATORY SYNCYTIAL VIRUS; LINKED TLR AGONISTS; IMMUNE-RESPONSES; DRUG-DELIVERY; CANCER-IMMUNOTHERAPY; CYTOKINE RELEASE; NANOPARTICLES; TOXICITY; NANOGELS; PROTEIN
作者：Van Herck, S; Van Hoecke, L; Louage, B; Lybaert, L; De Coen, R; Kasmi, S; Esser-Kahn, AP; David, SA; Nuhn, L; Schepens, B; Saelens, X; De Geest, BG
作者单位：比利时根特大学
期刊名称：BIOCONJUGATE CHEMISTRY
期刊影响因子：4.63
出版年份：2018
出版刊次：3
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