Subramaniyan Siva Bala, Vijayakumar Santhosh, Megarajan Sengan, Kamlekar Ravi Kanth, Anbazhagan Veerappan
School of Chemical & Biotechnology, SASTRA Deemed University, Thanjavur 613401, Tamil Nadu, India.
Department of Chemistry, School of Advance Sciences, VIT, Vellore 632014, Tamil Nadu, India.
ACS Omega. 2019 Aug 15;4(9):14049-14056. doi: 10.1021/acsomega.9b01886. eCollection 2019 Aug 27.
Herein, we report a new strategy based on jacalin functionalization to diminish the impact of biological fluids in the antibacterial applications of nanoparticles (NPs). Precoating pectin-capped copper sulfide NPs (pCuS) with bovine serum albumin produced a protein corona, which affects the antibacterial activity of pCuS. It was found that the minimum inhibitory concentration (MIC) increases fourfold because of the formation of the protein corona. Interestingly, the pCuS functionalized with jacalin enhance the targeting capabilities through bacterial cell surface glycan recognition with no interference from the protein corona. The MIC of pCuS decreases 16-fold on functionalization with jacalin. Mechanistic studies indicated that the pCuS functionalized with jacalin impede the protein corona interference and induce bacterial cell death by impairing the GSH/reactive oxygen species balance and disrupting the bacteria cell membrane. As a proof of concept, we used a bacteria-infected zebrafish animal model to demonstrate the interference of biological fluids in the antibacterial activity of NPs. Infected zebrafish treated with 1× MIC of pCuS failed to recover from the infection, but 4× MIC rescues the fish. The requirement of a high dose of NPs to treat the infection confirms the interference of biological fluids in nanotherapeutic applications. At the same time, the jacalin-pCuS complex rescues the infected fish at 16-fold lesser MIC. The results obtained from this study suggest that jacalin-mediated NP targeting may have broad implications in the development of future nanomedicine.
在此，我们报告了一种基于芝麻凝集素功能化的新策略，以减少生物流体对纳米颗粒（NPs）抗菌应用的影响。用牛血清白蛋白预包被果胶包覆的硫化铜纳米颗粒（pCuS）会产生蛋白质冠层，这会影响pCuS的抗菌活性。研究发现，由于蛋白质冠层的形成，最小抑菌浓度（MIC）增加了四倍。有趣的是，用芝麻凝集素功能化的pCuS通过细菌细胞表面聚糖识别增强了靶向能力，而不受蛋白质冠层的干扰。用芝麻凝集素功能化后，pCuS的MIC降低了16倍。机理研究表明，用芝麻凝集素功能化的pCuS可阻止蛋白质冠层的干扰，并通过破坏谷胱甘肽/活性氧平衡和破坏细菌细胞膜来诱导细菌细胞死亡。作为概念验证，我们使用细菌感染的斑马鱼动物模型来证明生物流体对NPs抗菌活性的干扰。用1×MIC的pCuS处理的感染斑马鱼未能从感染中恢复，但4×MIC可挽救鱼。治疗感染需要高剂量的NPs证实了生物流体在纳米治疗应用中的干扰。同时，芝麻凝集素-pCuS复合物在MIC低16倍的情况下挽救了感染的鱼。本研究获得的结果表明，芝麻凝集素介导的NP靶向可能在未来纳米医学的发展中具有广泛的意义。
