Cheng Ting-Yu, Chiu Yi-Chun, Chen Kuan-Hsu, Chen Ya-Jyun, Huang Chih-Chia
Department of Photonics, National Cheng Kung University, No. 1, University Road, Tainan 701, Taiwan.
Surgery, Taipei City Hospital Heping Fuyou Branch, Taipei 100, Taiwan.
J Mater Chem B. 2025 Jul 7. doi: 10.1039/d5tb00546a.
The biological application of silver nanoparticles (Ag NPs), which are commonly used as SERS substrates, is often limited by issues related to uncontrolled Ag ion release, resulting in instability and cytotoxicity. In this study, we developed galactosylated Ag@PGlyco-PSMA NPs, a novel biocompatible and bio-SERS platform for sensing small molecules at nanomolar concentration levels, achieving an analytical enhancement factor of 1.71 × 10 alongside intrinsic imaging and labeling capabilities for bladder cancer cells. These Ag NPs were co-synthesized during the polymerization of -nitrophenyl-β-D-galactopyranoside to form an Ag@polyaniline-based glycopolymer (PGlyco) nanostructure, which was subsequently reacted with poly(styrene--maleic acid) (PSMA). This process stabilized the particle dispersion while generating robust SERS signals due to PGlyco immobilization. By controlling the formation kinetics through the addition of the PSMA polymer at 30 seconds after the reaction of Ag@PGlyco NPs, we observed the formation of aggregate-induced hot spots to evolve PGlyco-related SERS signals arising from interparticle interactions. Our results demonstrated that Ag@PGlyco-PSMA NPs exhibit minimal Ag ion release, resulting in over 80% cell viability across T24, MB49, VERO, and SV-HUC-1 cell lines. Among these cells, Ag@PGlyco-PSMA nanoparticles demonstrated remarkable capability for enhancing cellular uptake, effectively distinguishing bladder cancer cells from normal cells with over 2.6 folds of the signal difference in SERS imaging. The galactose moieties in the PGlyco coating around the Ag@PGlyco-PSMA nanoparticles served as a SERS probe for multivalent binding to bladder cancer cells, enabling cancer imaging diagnosis and tumor-specific detection in accordance with tumor volume growth. Our findings indicated that Ag@PGlyco-PSMA nanoparticles offered intrinsic SERS capability for galactose-mediated bio-interaction and minimal Ag ion release, showing an ideal diagnostic optical platform for cancer cell imaging and tumor progression tracking through bladder SERS detection.
银纳米颗粒（Ag NPs）通常用作表面增强拉曼光谱（SERS）底物，其生物学应用常常受到与银离子不受控制释放相关问题的限制，从而导致不稳定性和细胞毒性。在本研究中，我们开发了半乳糖基化的Ag@PGlyco-PSMA NPs，这是一种新型的生物相容性和生物SERS平台，用于检测纳摩尔浓度水平的小分子，实现了1.71×10的分析增强因子，同时具备对膀胱癌细胞的固有成像和标记能力。这些Ag NPs在对硝基苯基-β-D-吡喃半乳糖苷聚合过程中共同合成，形成基于Ag@聚苯胺的糖聚合物（PGlyco）纳米结构，随后与聚（苯乙烯-马来酸）（PSMA）反应。由于PGlyco固定化，该过程稳定了颗粒分散，同时产生了强大的SERS信号。通过在Ag@PGlyco NPs反应30秒后添加PSMA聚合物来控制形成动力学，我们观察到聚集诱导热点的形成，以增强由颗粒间相互作用产生的与PGlyco相关的SERS信号。我们的结果表明，Ag@PGlyco-PSMA NPs的银离子释放量极低，在T24、MB49、VERO和SV-HUC-1细胞系中细胞活力超过80%。在这些细胞中，Ag@PGlyco-PSMA纳米颗粒表现出显著的增强细胞摄取能力，在SERS成像中能有效区分膀胱癌细胞和正常细胞，信号差异超过2.6倍。Ag@PGlyco-PSMA纳米颗粒周围PGlyco涂层中的半乳糖部分作为SERS探针，用于与膀胱癌细胞进行多价结合，能够根据肿瘤体积生长进行癌症成像诊断和肿瘤特异性检测。我们的研究结果表明，Ag@PGlyco-PSMA纳米颗粒具有用于半乳糖介导的生物相互作用的固有SERS能力，且银离子释放量极低，是通过膀胱SERS检测进行癌细胞成像和肿瘤进展跟踪的理想诊断光学平台。
