A tumor-responsive nanoprobebased on a conjugated
polyelectrolyte and gold nanoparticle (AuNP) hybrid wasdesigned to response to
the low pH extracellular microenvironment in tumor withlight-up fluorescence.
AuNPs with positive surface charges were prepared bydirect reducing Au salt
with sodium borohydride and stabilized by cystamine. ApH triggered
charge-reversible polymer and a water-soluble cationic
conjugatedpolyelectrolyte (CPE) were sequentially deposited onto the AuNP
surface throughelectrostatic interaction. The obtained hybrid probe is
monodispersed with anaverage diameter of 68.3 nm by dynamic light scattering
measurement. Inphysiological conditions (pH ≈7.4), thehybrid probe is almost
non-fluorescent due to the super-quenching of CPE by AuNPsvia energy/charge
transfer and efficient exciton migration along the polymerbackbone. When
exposed to acidic extracellular microenvironments in tumor (pHe ≈6.5), the
acid-labile amides hydrolyze into primary amines. Thegenerated amine groups
result in strong electrostatic repulsion between CPE andAuNPs, leading to
recovered probe fluorescence. The fluorescence turn-on isfurther utilized for
tumor extracellular acidic microenvironment imaging. Inaddition, under in vivo
conditions, the nanosized hybrid probe exhibitsspecific accumulation in tumor
tissue with light-up fluorescence, whichprovides new opportunities for easy
tumor imaging and identification.
Science突破发现：HIV老药可治疗黄斑变性
发布时间：2014-11-26 00:00 文章来源： 作者：
导读：近日，刊登在国际杂志Small上的一篇研究论文中，来自新加坡A*STAR研究所的研究人员开发了一种混合金属聚合物纳米颗粒，其在肿瘤细胞周围特殊的酸性环境下就会发光用以指示肿瘤所在，因此可以鉴别任何肿瘤的非特异性探针或许就可以用于监测癌症的发病部位、扩散及其疗法的有效性。
癌性肿瘤pH通常比正常的pH低，进而就会导致癌细胞内部和周围微环境中呈现酸性，正常细胞和肿瘤细胞之间的简单差异就可以帮助很多研究人员开发新型探针以利用光学成像和磁共振等技术来检测肿瘤的低pH微环境。然而许多靶向胞内pH的探针需要探针进入细胞内部来发挥作用，而一项巨大的挑战就是如何能够检测到正常细胞和肿瘤细胞胞外微环境的微小pH差异，一旦可以成功实现这种微小pH差异的检测就意味着探针并不需要进入细胞就可以检测出肿瘤细胞。
研究者Bin Liu说道，我们的目的就是开发可以实现上述目的的探针，文章中我们开发出了一种基于自组装的金纳米颗粒聚合物的新型探针，这种混合结构在正常的生理pH值之中是不会发荧光的，如果类似于肿瘤周围pH为6.5时的酸性环境就可以改变探针表面的化学基团从而开启探针的荧光。
在确定pH控制溶液的开关机制后，研究人员利用培养中的细胞和植入肿瘤的小鼠体内检测了这种新型探针的作用，在小鼠机体中注射探针后24小时，研究者利用全身性的成像技术或移除组织进行检查后，仅在小鼠肿瘤组织部位观察到了明显的荧光，这就显示这种新型探针或许可以在临床中用于人体试验。
最后研究者Liu表示：“到目前为止我们的新型探针具有很好的生物相容性，其对于生物医学应用领域非常关键；目前我们计划进一步检查探针对机体组织的毒性，并且在进行临床试验前评估探针在机体的生物分布性及药理学特性，我们相信该探针的开发为后期识别并且监测肿瘤的发展以有效控制癌症患者的病情会带来极大帮助。”
原文摘要：
A tumor-responsive nanoprobebased on a conjugated polyelectrolyte and gold nanoparticle (AuNP) hybrid wasdesigned to response to the low pH extracellular microenvironment in tumor withlight-up fluorescence. AuNPs with positive surface charges were prepared bydirect reducing Au salt with sodium borohydride and stabilized by cystamine. ApH triggered charge-reversible polymer and a water-soluble cationic conjugatedpolyelectrolyte (CPE) were sequentially deposited onto the AuNP surface throughelectrostatic interaction. The obtained hybrid probe is monodispersed with anaverage diameter of 68.3 nm by dynamic light scattering measurement. Inphysiological conditions (pH ≈7.4), thehybrid probe is almost non-fluorescent due to the super-quenching of CPE by AuNPsvia energy/charge transfer and efficient exciton migration along the polymerbackbone. When exposed to acidic extracellular microenvironments in tumor (pHe ≈6.5), the acid-labile amides hydrolyze into primary amines. Thegenerated amine groups result in strong electrostatic repulsion between CPE andAuNPs, leading to recovered probe fluorescence. The fluorescence turn-on isfurther utilized for tumor extracellular acidic microenvironment imaging. Inaddition, under in vivo conditions, the nanosized hybrid probe exhibitsspecific accumulation in tumor tissue with light-up fluorescence, whichprovides new opportunities for easy tumor imaging and identification.