Lin Wenjing, Hanson Samuel, Han Wenqing, Zhang Xiaofang, Yao Na, Li Hongru, Zhang Lijuan, Wang Chun
Department of Biomedical Engineering, University of Minnesota, 7-105 Hasselmo Hall, 312 Church Street S.E., Minneapolis, MN 55455, USA; School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China.
Department of Biomedical Engineering, University of Minnesota, 7-105 Hasselmo Hall, 312 Church Street S.E., Minneapolis, MN 55455, USA.
Acta Biomater. 2017 Jan 15;48:378-389. doi: 10.1016/j.actbio.2016.10.038. Epub 2016 Oct 27.
Co-delivery of antigen-encoding plasmid DNA (pDNA) and immune-modulatory molecules has importance in advancing gene-based immunotherapy and vaccines. Here novel star polymer nanocarriers were synthesized for co-delivery of pDNA and imiquimod (IMQ), a poorly soluble small-molecule adjuvant, to dendritic cells. Computational modeling and experimental results revealed that the polymers formed either multimolecular or unimolecular core-shell-type micelles in water, depending on the nature of the outer hydrophilic shell. Micelles loaded with both IMQ and pDNA were able to release IMQ in response to intracellular pH of the endo-lysosome and transfect mouse dendritic cells (DC2.4 line) in vitro. Importantly, IMQ-loaded micelle/pDNA complexes displayed much enhanced transfection efficiency than IMQ-free complexes. These results demonstrate the feasibility of co-delivery of pDNA and IMQ to antigen-presenting cells by multifunctional polymer nanocarriers with potential use in gene-based vaccine approaches.
共递送编码抗原的质粒DNA（pDNA）和免疫调节分子对于推进基于基因的免疫疗法和疫苗具有重要意义。在此，合成了新型星形聚合物纳米载体，用于将pDNA和咪喹莫特（IMQ，一种难溶性小分子佐剂）共递送至树突状细胞。计算模型和实验结果表明，根据外层亲水壳的性质，聚合物在水中形成多分子或单分子核壳型胶束。负载IMQ和pDNA的胶束能够响应内溶酶体的细胞内pH释放IMQ，并在体外转染小鼠树突状细胞（DC2.4系）。重要的是，负载IMQ的胶束/pDNA复合物比不含IMQ的复合物显示出更高的转染效率。这些结果证明了通过多功能聚合物纳米载体将pDNA和IMQ共递送至抗原呈递细胞的可行性，在基于基因的疫苗方法中具有潜在用途。
