Yuying Xu,Minting Liang,Jintao Huang,Yapei Fan,Haiyue Long,Qunjie Chen,Zhe Ren,Chaoxi Wu,Yifei Wang
Single helical β -glucan is a one-dimensional host that can form a hybrid helix with DNAs/RNAs as delivery systems. However, unmodified β -glucan has a gelling tendency and a single helical conformation is challenging to obtain. Therefore, in this study, we developed a β -glucan formyl derivative with stable single helical conformation and no gelling tendency. Circular dichroism studies found that the formyl- β -glucan could form a hybrid helix with DNA CpG-poly(dA). The hybrid helix delivery system showed improved activation on antigen-presenting cells, thereby upregulating the mRNA and protein levels of inflammatory factors, and had an immune-enhancing effect on ovalbumin (OVA) immunized mice. These results indicate that formyl- β -glucan can be developed as a non-cationic supramolecular DNA delivery platform with low toxicity and high efficiency.
The interaction between polydeoxyadenylic acid (poly(dA)) and single chains of Lentinan (s-LNT) was investigated by circular dichroism spectra (CD), UV–Vis spectra, nano-differential scanning calorimetry (nano-DSC), dynamic light scattering (DLS), and atomic force microscopy (AFM). All the experimental results indicated that poly(dA) really interacted with s-LNT having molecular weight of 5.3 × 10 5 to form a novel composite with stiff conformation through hydrogen bonding , whereas the triple helical Lentinan (t-LNT) could not, implying that it was the single chain but not the triple helical chain interacted with poly(dA). Meanwhile, the interaction strongly depended on the concentration of s-LNT and pH. When the poly(dA) concentration was fixed at 5.3 μg/ml, the interaction between poly(dA) and s-LNT increased with an increase in s-LNT concentration, then reached the maximum at ∼60 μg/ml, finally decreased with further increase of s-LNT concentration. This was due to self-renaturation of s-LNT into triple helix or incomplete species confirmed by nano-DSC. The poly(dA)/s-LNT complex could exist in solutions with pH 5.5–11.5, and pH 7–10 was the optimal condition for the complex, showing higher stability against pH than the positive control of poly(dA)/s-SPG. The dynamic behaviors of the complex demonstrated that the interaction between s-LNT and poly(dA) occurred rapidly, and reached stable within 3–7 h. Moreover, the thermal stability of poly(dA) was enhanced by complexation with s-LNT. The topograph of the poly(dA)/s-LNT complex was shown as rod-like stiff architecture. This work enlarges the application of LNT in the biomedical field.
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