An efficient system for intracellular delivery of beta-lactam antibiotics to overcome bacterial resistance.
An efficient system for intracellular delivery of beta-lactam antibiotics to overcome bacterial resistance.
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一个有效的系统，用于β-内酰胺抗生素的细胞内递送以克服细菌耐药性。
DOI：
10.1038/srep13500
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发表时间：
2015-08-27
影响因子：
4.6
通讯作者：
Couvreur P
中科院分区：
文献类型：
--
作者：
Abed N;Saïd-Hassane F;Zouhiri F;Mougin J;Nicolas V;Desmaële D;Gref R;Couvreur P
抗生素的“黄金时代”绝对是一个古老的故事，对于细胞内细菌感染尤其如此。抗生素的细胞内生物利用度差降低了许多治疗的效率，从而促进了耐药性。因此，纳米装置与抗生素结合的发展，能够靶向并将药物释放到受感染的细胞中，似乎是避免这些并发症的一个有希望的解决方案。在这里，我们利用两种天然萜烯（法尼基和香叶基）来设计纳米装置，用于有效地在细胞内递送青霉素g。萜烯部分和抗生素之间的共价键导致形成前药，其自组装形成具有55-63%高药物有效载荷的纳米颗粒。此外，在抗生素和萜烯之间添加环境敏感键导致对细胞内病原体金黄色葡萄球菌具有有效的抗菌活性，与未处理的感染细胞相比，细胞内复制减少约99.9%。通过高效液相色谱分析，我们证明并量化了前药上存在这种敏感键（SB）时PenG的细胞内释放，表明该技术成功地将抗生素直接输送到细胞中。
The “Golden era” of antibiotics is definitely an old story and this is especially true for intracellular bacterial infections. The poor intracellular bioavailability of antibiotics reduces the efficency of many treatments and thereby promotes resistances. Therefore, the development of nanodevices coupled with antibiotics that are capable of targeting and releasing the drug into the infected-cells appears to be a promising solution to circumvent these complications. Here, we took advantage of two natural terpenes (farnesyl and geranyl) to design nanodevices for an efficient intracellular delivery of penicillin G. The covalent linkage between the terpene moieties and the antibiotic leads to formation of prodrugs that self-assemble to form nanoparticles with a high drug payload between 55–63%. Futhermore, the addition of an environmentally-sensitive bond between the antibiotic and the terpene led to an efficient antibacterial activity against the intracellular pathogen Staphylococcus aureus with reduced intracellular replication of about 99.9% compared to untreated infected cells. Using HPLC analysis, we demonstrated and quantified the intracellular release of PenG when this sensitive-bond (SB) was present on the prodrug, showing the success of this technology to deliver antibiotics directly into cells.