Human
choroidal melanoma (HCM) is one of the most common primary intraocular
tumors and easily provokes liver metastases owing to the lack of sensitive
and noninvasive therapeutic methods. Concerning the imaging diagnostics
and therapeutic predicaments for choroidal melanoma, we designed microenvironment-triggered
degradable hydrogels (RENP-ICG@PNIPAM:Dox-FA) based on ultrasmall
(<5 nm) rare-earth nanoparticles (RENPs) with enhanced NIR-II luminescence.
The ultrasmall diameter can significantly enhance the NIR-II luminescence
performance of RENPs. RENPs were encapsulated by a dual-response PNIPAM
hydrogel, which could release drug by responding to heat energy and
glutathione under the tumor microenvironment. The in vitro/in vivo NIR-II imaging detection and antitumor
activity were also compared systematically after different treatment
conditions on ocular choroidal melanoma-1 cells and tumor-bearing
mice, respectively. Besides, the degradability of the hydrogel composites
under physiological conditions could be conducive to enhance the photothermal–chemotherapeutic
effect and alleviate long-term biological toxicity. Our work on the
microenvironment-triggered hydrogels with enhanced NIR imaging and
easy metabolism may provide a promising strategy for sensitive and
noninvasive imaging and phototherapy in ocular tumors.
Mechanistic roles of dopant concentrations in excited-state population and quenching in upconversion luminescence are investigated based on nonexponentiality-revisiting kinetics.
Herein, a functional class of microenvironmentassociated nanomaterials is reported for improving the second near-infrared (NIR-II) imaging and photothermal therapeutic effect on intracranial tumors via a spontaneous membraneadsorption approach. Specific peptides, photothermal agents, and biological alkylating agents were designed to endow the nanogels with high targeting specificity, photothermal properties, and pharmacological effects. Importantly, the frozen scanning electron microscopy technology (cryo-SEM) was utilized to observe the self-association of nanomaterials on tumor cells. Interestingly, the spontaneous membrane-adsorption behavior of nanomaterials was captured through direct imaging evidence. Histological analysis showed that the crosslinking adhesion in intracranial tumor and monodispersity in normal tissues of the nanogels not only enhanced the retention time but also ensured excellent biocompatibility. Impressively, in vivo data confirmed that the microenvironment-associated nanogels could significantly enhance brain tumor clearance rate within a short treatment timeframe (only two weeks). In short, utilizing the spontaneous membrane-adsorption strategy can significantly improve NIR-II diagnosis and phototherapy in brain diseases while avoiding high-risk complications.
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