State Key Laboratory of Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, Nanjing 210023, China.
State Key Laboratory of Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, Nanjing 210023, China.
J Colloid Interface Sci. 2024 Jan 15;654(Pt A):740-752. doi: 10.1016/j.jcis.2023.10.038. Epub 2023 Oct 12.
Nanotheranostic agents combined the second near-infrared (NIR-II, 1000-1700 nm) fluorescence imaging with phototherapy strategy have attracted tremendous interest. However, the actual efficacy of NIR-II probes could be weakened by their limited accumulation and penetration in tumor tissues. Herein, a size-transformable NIR-II nanotheranostic agent (BBT-HASS@FPMPL NPs) is employed for simultaneously enhanced penetration and retention in deep tumor tissue to realize precise image and effective PTT therapy. BBT-HASS@FPMPL NPs were first formed by using hyaluronic acid (HA) chains and disulfide bonds as stimuli-responsive "lock" to efficiently load conjugated oligomer (BBTN), and then folic acid (FA) modified polylysine (FPMPL) shell was stacked at the surface by electrostatic interaction. Dual targeting with HA and FA is expected to lead to more selective targeting and better accumulation of BBT-HASS@FPMPL NPs in tumor sites. Simultaneously, obvious particle size reduction and charge reversal can be triggered in acidic tumor microenvironment to achieve deep intratumor filtration through transcytosis. Following tumor penetration, size change was further initiated by overexpressed hyaluronidase and GSH in tumor. Free BBTN can be subsequently released from nanoparticles to promote specific intratumor retention, which synergistically enhance photothermal therapeutic efficacy. Owing to sufficient tumor accumulation and deep penetration, the NIR-II emission of BBTN could further be used for precise monitoring of subcutaneous tumor progression in mice for 6 days with just one dose injection. We expect that such nanotheranostic platform that combined the high resolution of NIR-II fluorescence with deep tumor penetration and long intratumor retention could be useful for real-time monitoring of tumor process, precise diagnosis, and enhanced phototherapy.
纳米诊疗试剂将第二代近红外（NIR-II，1000-1700nm）荧光成像与光疗策略相结合，引起了极大的兴趣。然而，NIR-II 探针的实际疗效可能会因其在肿瘤组织中的有限积累和穿透而减弱。在此，我们采用了一种尺寸可转换的 NIR-II 纳米诊疗试剂（BBT-HASS@FPMPL NPs），用于同时增强深层肿瘤组织中的穿透和保留，以实现精确的成像和有效的 PTT 治疗。BBT-HASS@FPMPL NPs 首先由透明质酸（HA）链和二硫键作为刺激响应“锁”来有效地装载共轭低聚物（BBTN）形成，然后通过静电相互作用在表面堆叠叶酸（FA）修饰的聚赖氨酸（FPMPL）壳。HA 和 FA 的双重靶向作用有望导致 BBT-HASS@FPMPL NPs 在肿瘤部位更具选择性的靶向和更好的积累。同时，在酸性肿瘤微环境中可以触发明显的粒径减小和电荷反转，通过转胞作用实现深层肿瘤内过滤。肿瘤穿透后，肿瘤中过表达的透明质酸酶和 GSH 进一步引发粒径变化。然后，游离的 BBTN 可以从纳米颗粒中释放出来，促进肿瘤内的特异性保留，从而协同增强光热治疗效果。由于充分的肿瘤积累和深层穿透，BBTN 的 NIR-II 发射可进一步用于仅通过一次剂量注射即可对小鼠皮下肿瘤进展进行精确监测 6 天。我们期望这种将 NIR-II 荧光的高分辨率与深层肿瘤穿透和长肿瘤内保留相结合的纳米诊疗平台，可用于实时监测肿瘤过程、精确诊断和增强光疗。
