Bioengineering stimuli-responsive organic-inorganic nanoarchitetures based on carboxymethylcellulose-poly-l-lysine nanoplexes: Unlocking the potential for bioimaging and multimodal chemodynamic-magnetothermal therapy of brain cancer cells.

Regrettably, glioblastoma multiforme (GBM) remains the deadliest form of brain cancer, where the early diagnosis plays a pivotal role in the patient's therapy and prognosis. Hence, we report for the first time the design, synthesis, and characterization of new hybrid organic-inorganic stimuli-responsive nanoplexes (NPX) for bioimaging and killing brain cancer cells (GBM, U-87). These nanoplexes were built through coupling two nanoconjugates, produced using a facile, sustainable, green aqueous colloidal process ("bottom-up"). One nanocomponent was based on cationic epsilon-poly-l-lysine polypeptide (εPL) conjugated with ZnS quantum dots (QDs) acting as chemical ligand and cell-penetrating peptide (CPP) for bioimaging of cancer cells (QD@εPL). The second nanocomponent was based on anionic carboxymethylcellulose (CMC) polysaccharide surrounding superparamagnetic magnetite "nanozymes" (MNZ) behaving as a capping macromolecular shell (MNZ@CMC) for killing cancer cells through chemodynamic therapy (CDT) and magnetohyperthermia (MHT). The results demonstrated the effective production of supramolecular aqueous colloidal nanoplexes (QD@εPL_MNZ@CMC, NPX) integrated into single nanoplatforms, mainly electrostatically stabilized by εPL/CMC biomolecules with anticancer activity against U-87 cells using 2D and 3D spheroid models. They displayed nanotheranostics (i.e., diagnosis and therapy) behavior credited to the photonic activity of QD@εPL with luminescent intracellular bioimaging, amalgamated with a dual-mode killing effect of GBM cancer cells through CDT by nanozyme-induced biocatalysis and as "nanoheaters" by magnetically-responsive hyperthermia therapy.