Yin Chang, Wei Zi-Jin, Long Kai, Sun Mengjie, Zhang Zhouyu, Wang Yifei, Wang Wei, Yuan Zhi
Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071, China.
ACS Appl Mater Interfaces. 2024 Dec 18;16(50):69071-69085. doi: 10.1021/acsami.4c17747. Epub 2024 Dec 8.
Owing to autofluorescence-free feature, persistent luminescent (PersL) nanoparticles (PLNPs) become potential materials for tumor surgical navigation. However, it is still challenging to enhance PersL intensity, contrast ratio, and imaging stability so as to meet clinical demand and avoid missed detection of microlesions. Herein, integrating a tumor microenvironment (TME)-responsive strategy, sensitization enhancement, and internal-standard ratiometric method, a dual-mode PersL imaging strategy is proposed: After loading pH-responsive fluorescent molecule Rh-ADM on PLNPs ZnGaO:Cr,Mn (ZGCM-Rh8), the fluorescence resonance energy transfer (FRET) pathways between Cr and Rh-ADM, as well as Mn and Rh-ADM, could sensitize the NIR PersL emitted by Cr and quench the green PersL from Mn at acidic TME, respectively. As a result, ZGCM-Rh8 is endowed with WLED (white light LED)-excited NIR imaging mode and UV-excited ratiometric imaging mode. Under WLED, ZGCM-Rh8 realizes 4.5-fold PersL enhancement and 97.9 as the maximum tumor contrast after precise control of Rh-ADM contents, helping with the preoperative diagnosis of deep lesions. Under UV, ZGCM-Rh8 conducts ratiometric PersL imaging steadily, and the "NIR/Vis" ratios at the tumor keep larger than 110, succeeding in detecting out a 1.5 mm small lesion and serving thorough surgical elimination of H22 ectopic intramuscular tumor in balb/c mice. To our knowledge, ZGCM-Rh8 is the first to realize pH-responsive PersL sensitization and apply ratiometric PersL imaging technology to surgical navigation.
由于无自发荧光特性，持续发光（PersL）纳米颗粒（PLNPs）成为肿瘤手术导航的潜在材料。然而，提高PersL强度、对比度和成像稳定性以满足临床需求并避免漏诊微病变仍然具有挑战性。在此，通过整合肿瘤微环境（TME）响应策略、敏化增强和内标比率法，提出了一种双模式PersL成像策略：在PLNPs ZnGaO:Cr,Mn（ZGCM-Rh8）上负载pH响应荧光分子Rh-ADM后，Cr与Rh-ADM以及Mn与Rh-ADM之间的荧光共振能量转移（FRET）途径可分别在酸性TME中敏化Cr发射的近红外PersL并淬灭Mn发出的绿色PersL。结果，ZGCM-Rh8具有白光发光二极管（WLED）激发的近红外成像模式和紫外激发的比率成像模式。在WLED下，精确控制Rh-ADM含量后，ZGCM-Rh8实现了4.5倍的PersL增强，最大肿瘤对比度达到97.9，有助于深部病变的术前诊断。在紫外光下，ZGCM-Rh8稳定地进行比率PersL成像，肿瘤处的“近红外/可见光”比率保持大于110，成功检测出1.5毫米的小病变，并彻底切除了balb/c小鼠体内的H22异位肌内肿瘤。据我们所知，ZGCM-Rh8是首个实现pH响应PersL敏化并将比率PersL成像技术应用于手术导航的材料。
