College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University, Jinan 250014, People's Republic of China.
ACS Appl Bio Mater. 2021 Feb 15;4(2):1740-1748. doi: 10.1021/acsabm.0c01504. Epub 2021 Jan 20.
Photodynamic therapy (PDT) is a promising therapeutic approach that has been extensively applied in curing cancers. However, the limited penetration depth of external light makes PDT only practical for some superficial tumor treatments. Moreover, an external light irradiation might cause damages to adjacent normal tissues. Additionally, the poor targeting ability of PDT can lead to side effects like skin phototoxicity. Therefore, a PDT strategy addressing these drawbacks is urgently exploited. Herein, we constructed a chemiluminescence theranostics platform named MSN@HL@β-CD@AMPPD NPs for liver cancer-specific, diagnosis and therapy without an external light source. Through the interaction of host-guest, 3-[(2-spiroadamatane)-4-methoxy-4-(3-phosphoryloxy)-phenyl-1,2-dioxetane] dioxetane, a chemiluminescence substrate of the liver cancer biomarker alkaline phosphatase was integrated with β-cyclodextrin. Then, the β-cyclodextrin was covalently bound to the mesoporous silica loaded with (4-carboxyphenyl) porphyrin to finally obtain the MSN@HL@β-CD@AMPPD NPs. These NPs can be specifically hydrolyzed by the liver cancer alkaline phosphatase and lead to the liver cancer-targeting chemiluminescence. Subsequently, (4-carboxyphenyl) porphyrin was excited by the chemiluminescence through chemiluminescence resonance energy transfer and created both near-infrared fluorescence and O. This strategy greatly promotes the penetration depth and targeting ability of the PDT. In brief, the platform accomplishes a PDT nano-theranostics for liver cancer and provides a method for the imaging, diagnosis, and therapy of tumors in deep tissue.
光动力疗法（PDT）是一种很有前途的治疗方法，已广泛应用于癌症的治疗。然而，外部光的有限穿透深度使得 PDT 仅适用于一些浅表肿瘤的治疗。此外，外部光照射可能会对相邻的正常组织造成损伤。此外，PDT 的靶向能力差可能会导致皮肤光毒性等副作用。因此，迫切需要开发一种解决这些缺点的 PDT 策略。在此，我们构建了一种名为 MSN@HL@β-CD@AMPPD NPs 的化学发光诊疗平台，用于肝癌的特异性诊断和治疗，无需外部光源。通过主体-客体相互作用，将肝癌生物标志物碱性磷酸酶的化学发光底物 3-[[2-螺环戊烷]-4-甲氧基-4-(3-膦酰氧基)-苯基-1,2-二氧杂环乙烷]二氧杂环乙烷与β-环糊精结合。然后，β-环糊精与负载（4-羧基苯基）卟啉的介孔硅结合，最终得到 MSN@HL@β-CD@AMPPD NPs。这些 NPs 可以被肝癌碱性磷酸酶特异性水解，导致肝癌靶向化学发光。随后，化学发光通过化学发光共振能量转移激发（4-羧基苯基）卟啉，产生近红外荧光和 O2。该策略大大提高了 PDT 的穿透深度和靶向能力。总之，该平台实现了肝癌的 PDT 纳米诊疗，为深部组织肿瘤的成像、诊断和治疗提供了一种方法。
