生物被膜（BF）是鲍曼不动杆菌（AB）发生耐药，导致抗生素治疗失败的重要原因，因此治疗中我们考虑联用多粘菌素（PB）和抗BF肽IDR-1018（I1）。但要增加药物的BF穿透性，并实现精准药物配比，进而强化药物协同作用、降低毒性，选择合适的共递送载体是关键问题。目前常用载体有脂质体和高分子材料，但均存在粒径大、无法精准控制联用药物比例等问题。DNA四面体（Td）是一类体积小、设计灵活的新载体。我们前期发现，Td可穿透AB菌膜，携带反义核酸入菌抑制靶基因表达，且有BF穿透性，提示Td可作为针对BF生成型耐药AB（BF-DRAB）的高效载体。本课题拟利用碱基互补配对，调控Td粒径以及PB和I1的配比，筛选出BF穿透性最佳的Td粒径，并优化PB和I1比例，最终制备出能高效穿透BF，进而分散BF且杀灭细菌的PB-I1@Td，并在体内外评价其有效性及安全性，旨在为抗BF-DRAB感染寻找新的突破口。

Bacterial biofilm (BF) is a crucial factor of making A. baumannii (AB) resistant to drugs and causing treatment failure of antibiotics. To solve this problem, we want to combine polymyxin B (PB) and anti-biofilm peptide IDR-1018 (I1). However, because of the need to enhance the drug synergism and reduce the drug toxicity, it matters to choose a proper co-delivery carrier in order to increase biofilm penetrability and adjust ratios accurately of both drugs. Now, liposome and polymer materials are frequently-used carriers, which have some disadvantages such as big size and inability to control the drug ratios. DNA tetrahedron (Td), as a new type of carrier, is charactered by its small size and flexible design. We have demonstrated that Td could penetrate bacterial membrane of AB and deliver antisense oligonucleotides into bacteria to inhibit target genes. And it was also found that Td had the ability to penetrate the biofilm. All results implies that Td has the potential to be a drug carrier for combating the drug-resistant AB forming the biofilm (BF-DRAB). In this project, we adjust Td size and ratios of PB and I1 by taking advantage of DNA base pairing, and then select the Td with the best biofilm penetrability as well as optimize the ratios between PB and I1. Furthermore, PB-I1@Td with strong penetrability is prepared, which can disperses biofilm and kills bacteria. And the efficiency and safety of PB-I1@Td are evaluated in vitro and in vivo. This project aims to open a novel avenue for treating BF-DRAB.