Abstract
Quantum dots (QDs) bring new insights in cancer theranostics. Exceptional brightness together with the simple possibility to modify surface with targeting molecules make QDs attractive agents in fluorescence guided surgery and photodynamic therapy. Currently, many targeted QDs have been developed for theranostic purpose. However, their targeting ability was tested mainly in two dimensional monolayer tumor cell models, while our study includes 3D tumor model reflecting the specificity of in vivo tumor environment. Core/multilayer shell CdSe/CdS/ZnS QDs were conjugated with folic acid (FA) and characterized spectroscopically. Cytotoxicity of QDs on KB and A549 cells lines were evaluated using the MTT assay. Cellular uptake of QDs was assessed by epifluorescent microscopy. To study the distribution of QDs in tumor tissue, KB spheroids were prepared by means of the liquid overlay technique and then frozen cut of spheroids treated with QDs were imaged by epifluorescence microscopy. We confirmed the specificity of QD-FA for the folic acid receptor positive KB cells. In 3D tumor spheroid model we demonstrated uptake enhancement of QD-FA compared with non-targeted QD. It was demonstrated that penetration profiles were similar for both QDs with penetration depth never exceeding 100 μm. We have demonstrated the effectiveness of FA conjugated QDs to target tumor spheroids thus confirming the crucial role of FRα receptor as a target. Further improvement of QD-FA targeting ability could be performed using dual targeting different targeting agents, such as FA and cyclic RGD.
Highlights
Cancer is the second most important cause of death worldwide [1]
Current therapeutic improvements are mainly related to tumor targeting with nanoparticles (NPs), which show superior properties compared with routine drugs
We developed the Quantum dots (QDs) conjugated to folic acid (FA) and assessed their targeting ability in multicellular tumor spheroids (MCTSs) made from folate receptor-α (FR-α)-positive oral cancer cells (KB)
Summary
Current therapeutic improvements are mainly related to tumor targeting with nanoparticles (NPs), which show superior properties compared with routine drugs. NPs display improved tumor accumulation through both passive and active targeting, large surface to volume ratio and versatile surface chemistry. They can associate therapeutics and imaging capabilities of drugs with theranostic aims [2]. We used QDs coated by a zwitterionic copolymer ligand to assess the improvement of QD selectivity upon their conjugation with folic acid (FA) as a targeting agent. We developed the QDs conjugated to FA and assessed their targeting ability in MCTSs made from FR-α-positive oral cancer cells (KB). In the parallel we evaluated QDs uptake in conventional monolayer cells model
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
