Abstract
Among almost 200 types of cancers, glioma is considered one of the most common forms of malignant tumors located in the central nervous system (CNS). Glioblastoma (GBM), one of the deadliest types of brain cancer, remains one of the challenges faced by oncologists. Thus, smartly designed nanomaterials biofunctionalized with polypeptides can offer disruptive strategies relying on the earliest possible diagnosis ("seeing is believing") combined with more efficient therapies for fighting cancer cells. To worsen this scenario, bacteria infections very often pose a serious challenge to cancer-immunodeficient patients under chemotherapy. Thus, in this research, we report for the first time the design and synthesis of novel nanoconjugates composed of photoluminescent ZnS quantum dots (ZnS QDs), which were directly surface biofunctionalized with epsilon-poly-l-lysine (εPL), acting as an amine-rich cell-penetrating peptide (CPP) and antimicrobial peptide agent (AMP). These nanoconjugates (named ZnS@CPP-AMP) were produced through a one-step facile, eco-friendly, and biocompatible colloidal aqueous process to be applied as a proof of concept as nanoprobes for bioimaging GBM cancer cells (U87-MG) associated with synergic antibacterial activity. They were characterized regarding their physicochemical and optical properties associated with the biological activity. The results demonstrated that chemically stable aqueous colloidal nanoconjugates were effectively formed, resembling core-shell (inorganic, ZnS, organic, εPL) nanostructures with positively surface-charged features due to the cationic nature of the amine-rich polypeptide. More importantly, they demonstrated photoluminescent activity, cytocompatibility in vitro, and no significant intracellular reactive oxygen species (ROS) generation. These ZnS@CPP-AMP nanocolloids behaved as fluorescent nanoprobes for bioimaging GBM cancer cells, where the polycationic nature of the εPL biomolecule may have enhanced the cellular uptake. Additionally, they displayed mild antibacterial growth inhibition due to electrostatic interactions with bacterial membranes. Thus, it can be envisioned that these novel photoluminescent colloidal nanoconjugates offer novel nanoplatforms that can be specifically targeted with biomolecules for bioimaging to diagnose highly lethal cancers, such as GBM, and as an adjuvant in antibacterial therapy.
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