Fluorescent gold nanoclusters (AuNCs) with emission in near infrared (NIR) range have drawn wide attention due to its bright fluorescence, good biocompatibility and photostability. In this work, AuNCs with emission at 800 nm were synthesized through a simple glutathione reduction method through heating. Cyclic RGD peptide will be conjugated through thiol-PEG-amine as targeting ligand. The AuNCs are then used for two photon fluorescent imaging, due to the wide stokes shift. In vivo NIR fluorescent study showed the accumulation of the AuNCs in tumor areas. Moreover, the AuNCs also showed brain uptake, which indicates possible applications in brain imaging.
LS301 is a promising NIR fluorescence probe for targeting brain glioma cancer. The co-localization of LS31 and 5-ALA induced PpIX in vitro and in vivo enables LS301 to guide PpIX fluorescence image surgery. Moreover, LS301 showed no negative impact on 5-ALA-PpIX PDT outcome in brain glioma cells and mouse tumor model. Therefore, the implementation of LS301 and PpIX has potential to improve tumor resection surgery and PDT treatment for better tumor outcomes.
Significance: The blood–brain barrier (BBB) is a major obstacle to detecting and treating brain tumors. Overcoming this challenge will facilitate the early and accurate detection of brain lesions and guide surgical resection of tumors.
Aim: We generated an orthotopic brain tumor model that simulates the pathophysiology of gliomas at early stages; determine the BBB integrity and breakdown over the time course of tumor progression using generic and cancer-targeted near-infrared (NIR) fluorescent molecular probes.
Approach: We developed an intracranial tumor xenograft model that rapidly reestablished BBB integrity and monitored tumor progression by bioluminescence imaging. Sham control mice were injected with phosphate-buffered saline only. Fluorescence molecular tomography (FMT) was used to quantify the uptake of tumor-targeted and passive NIR fluorescent imaging agents in orthotopic glioma (U87-GL-GFP PDE7B H217Q cells) tumor model. Cancer-induced and transient (with focused ultrasound, FUS) disruption of BBB integrity was monitored with NIR fluorescent dyes.
Results: Stereotactic injection of 50,000 cells into mouse brain allowed rapid reestablishment of BBB integrity within a week, as determined by the inability of both tumor-targeted and generic NIR imaging agents to extravasate into the brain. Tumor-induced BBB disruption was observed 7 weeks after tumor implantation. FUS achieved a similar effect at any time point after reestablishing BBB integrity. While tumor uptake and retention of the passive NIR dye, indocyanine green, was negligible, both actively tumor-targeting agents exhibited selective accumulation in the tumor region. The tumor-targeting molecular probe that clears rapidly from nontumor brain tissue exhibits higher contrast than the analogous vascular-targeting agent and helps delineate tumors from sham control.
Conclusions: We highlight the utility of FMT imaging for longitudinal assessment of brain tumors and the interplay between the stages of BBB disruption and molecular probe retention in tumors, with potential application to other neurological diseases.
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