PDF(Pubmed)
Abstract：
Poly(amidoamine) (PAMAM) dendrimers have attracted considerable attention in the field of gene therapy due to their flexibility in introducing different functional moieties and reduced toxicity at low generations. However, their transfection efficiency remains a limitation. Therefore, an essential approach for improving their transfection efficiency as gene carriers involves modifying the structure of PAMAM by conjugating functional groups around their surface. In this study, we successfully conjugated an RRHRH oligopeptide to the surface of PAMAM generation 2 (PAMAM G2) to create RRHRH-PAMAM G2. This construction aims to condense plasmid DNA (pDNA) and facilitate its penetration into cell membranes, leading to its promising potential for gene therapy. RRHRH-PAMAM G2/pDNA complexes were smaller than 100 nm and positively charged. Nano-polyplexes can enter the cell and show a high transfection efficiency after 24 h of transfection. The RRHRH-PAMAM G2 was non-toxic to HeLa, NIH3T3, A549, and MDA-MB-231 cell lines. These results strongly suggest that RRHRH-PAMAM G2 holds promise as a gene carrier for gene therapy owing to its biocompatibility and ability to deliver genes to the cell.
摘要：
聚(酰胺基胺)(PAMAM)树枝状聚合物由于其在引入不同功能部分方面的灵活性和在低世代时降低的毒性而在基因治疗领域中引起了相当大的关注。然而,它们的转染效率仍然受到限制。因此,作为基因载体，提高其转染效率的重要方法包括通过缀合其表面周围的官能团来修饰PAMAM的结构。在这项研究中,我们成功地将RRHRH寡肽缀合至PAMAM第2代(PAMAMG2)的表面以产生RRHRH-PAMAMG2。该构建旨在浓缩质粒DNA（pDNA）并促进其渗透到细胞膜中，导致其在基因治疗方面有前途的潜力。RRHRH-PAMAMG2/pDNA复合物小于100nm，带正电荷。纳米复合物可以进入细胞并在转染24小时后显示出高转染效率。RRHRH-PAMAMG2对HeLa无毒，NIH3T3、A549和MDA-MB-231细胞系。这些结果强烈表明RRHRH-PAMAMG2由于其生物相容性和将基因递送到细胞的能力而有望作为基因治疗的基因载体。
