Macrophages Loaded With Gold Nanorods For The Integration Of Diagnosis And Treatment Of Tumor Hypoxic Areas

Gold nanoroads are emerging as promising candidates for precision medical treatment on tumor due to strong near infrared absorption,high conversion efficiency of heat,integrating multiple image features,and so on.However,there exist several problems when applying these gold nanorods for in vivo applications,such as potential long-term toxicity due to difficulty cleared out from the body and the poor treatment effect of hypoxic area.In order to solve these problems,we report a strategy to synthesize ultra-small gold nanorods(a width less than 6 nm and a length of about 25 nm)with renal clearance and strong near infrared absorption.In order to further increase its biological compatibility,polyethylene glycol(PEG)was used to modify the gold nanorods.Subsequently,we employed macrophage vehicles to transport the ultra-small gold nanorods to the tumor hypoxic area for improving the therapeutic effect.Lastly,using the photoacoustic imaging technology,we further explore the macrophage on how to overcome biological barriers to improve the delivery of diagnosis reagents and therapeutic effect of cancer,which provides a new idea for the treatment of tumors.This article mainly includes the following contents:Firstly,one scale-up seedless method is developed to prepare the ultra-small gold nanorods with uniform particle size and strong near-infrared absorption properties.Then,PEG was used to replace the hexadecyl trimethyl ammonium bromides(CTAB)which cover on the surface of the gold nanorods to further improve the biocompatible of the ultra-small gold nanorods.At last,three kinds of gold nanorods with different surface charges were obtained by ligand exchange.Secondly,the biocompatibility of the gold nanorods with different surface charges was investigated.The results suggested that cationic gold nanorods have high biological toxicity,while neutral and anionic gold nanorods have good biological compatibility.Subsequently,we investigated the cellular uptake of the neutral and anionic gold nanorods.The results showed that the cellular uptake of anionic gold nanorods is larger than the neutral gold nanorods.After the macrophages loaded with anionic gold nanorods,the biological activity for macrophages and near infrared absorption of the gold nanorods was investigated,respectively.The result proved Anionic-Au-NR-laden-macrophages still has good biological activity and good near infrared absorption.Thirdly,in order to explore the therapeutic effect for hypoxic region of the tumor by the Anionic-Au-NR-laden-macrophages,the targeted properties of the tumor in the hypoxic region was studied by the photoacoustic imaging and tissue slice technique.The results showed that macrophages can carry the anionic gold nanorods to the tumor hypoxic region,which lays a foundation for improving the therapeutic effect of the tumor.Fourthly,the treatment of tumor hypoxic region is one of the effective ways to improve the therapeutic effect of the tumor.Therefore,we preliminary explored the treatment of tumor hypoxic region by Anionic-Au-NR-laden-macrophages.Compared with free Anionic-Au-NR,the Anionic-Au-NR-laden-macrophages exhibited more excellent antitumor efficiency.As a result,the tumor recurrence rate of the Anionic-Au-NR-laden-macrophages was reduced by 37.5% and the survival rate increased by 37.5%.These results suggest macrophage loaded ultra-small gold nanorods can effectively improve the therapeutic effect of tumor.