Kaihe Lv,Haokun Shen,Jinsheng Sun,Xianbin Huang,Hongyan Du
Shale hydration dispersion and swelling are primary causes of wellbore instability in oil and gas reservoir exploration. In this study, inulin, a fructo-oligosaccharide extracted from Jerusalem artichoke roots, was modified by acylation with three acyl chlorides, and the products (C10-, C12-, and C14-inulin) were investigated for their use as novel shale hydration inhibitors. The inhibition properties were evaluated through the shale cuttings hot-rolling dispersion test, the sodium-based bentonite hydration test, and capillary suction. The three acylated inulins exhibited superb hydration-inhibiting performance at low concentrations, compared to the commonly used inhibitors of KCl and poly (ester amine). An inhibition mechanism was proposed based on surface tension measurements, contact angle measurements, Fourier-transform infrared analysis, and scanning electron microscopy. The acylated inulin reduced the water surface tension significantly, thus, retarding the invasion of water into the shale formation. Then, the acylated inulin was adsorbed onto the shale surface by hydrogen bonding to form a compact, sealed, hydrophobic membrane. Furthermore, the acylated inulins are non-toxic and biodegradable, which meet the increasingly stringent environmental regulations in this field. This method might provide a new avenue for developing high-performance and ecofriendly shale hydration inhibitors.
Cancer vaccines utilizing nanoparticle (NP) structures that integrate antigens and adjuvants to enhance delivery and stimulate immune responses are emerging as a promising avenue in cancer immunotherapy. However, the development of cancer vaccines has been significantly hindered by the low immunogenicity of tumor antigens. To address this challenge, substantial efforts have been made in developing innovative adjuvants to elicit effective immune responses. In this study, we develop a NP cancer vaccine assisted by a polysaccharide derivative adjuvant, designed through a computational strategy, to evoke effective antigen-specific antitumor immunity. Using TLR4 as the putative receptor, we conducted a comprehensive evaluation of a prescreening library consisting of 34 inulin derivatives through docking and molecular dynamics simulation. Consequently, a new derivative, benzoylated inulin (InBz), is selected as the most promising TLR4 agonist. The adjuvant effect of InBz is evaluated by fabricating InBz NPs encapsulating the model antigen ovalbumin (OVA). In vitro, InBz-OVA NPs effectively activate the TLR4 signaling pathways and facilitate dendritic cell maturation, thereby enhancing the antigen delivery and presentation. In vivo, InBz-OVA NPs outperform a commercial aluminum-based adjuvant, elicit robust antibody titers, induce antigen-specific cytotoxic T lymphocytes, and achieve significant tumor suppression in murine models. Besides, the adjuvant effects of other representative derivatives, namely, acetylated and chloroacetylated inulin, with moderate and low potential from the library, are also chemically synthesized and experimentally evaluated and found to be in agreement with computational predictions, confirming the credibility of the strategy. This study provides an effective platform for the pursuit of efficient polysaccharide-based vaccine adjuvants.
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