Carboxymethylcellulose biofunctionalized ternary quantum dots for subcellular-targeted brain cancer nanotheranostics.

Among the most lethal forms of cancer, malignant brain tumors persist as one of the greatest challenges faced by oncologists, where nanotechnology-driven theranostics can play a critical role in developing novel polymer-based supramolecular nanoarchitectures with multifunctional and multi-modal characteristics to fight cancer. However, it is virtually a consensus that, besides the complexity of active delivering anticancer drugs by the nanocarriers to the tumor site, the current evaluation methods primarily relying on in vitro assays and in vivo animal models have been accounted for the low translational effectiveness to clinical applications. In this view, the chick chorioallantoic membrane (CAM) assay has been increasingly recognized as one of the best preclinical models to study the effects of anticancer drugs on the tumor microenvironment (TME). Thus, in this study, we designed, characterized, and developed novel hybrid nanostructures encompassing chemically functionalized carboxymethylcellulose (CMC) with mitochondria-targeting pro-apoptotic peptide (KLA) and cell-penetrating moiety (cysteine, CYS) with fluorescent inorganic semiconductor (Ag-In-S, AIS) for simultaneously bioimaging and inducing glioblastoma cancer cell (U-87 MG, GBM) death. The results demonstrated that the CMC-peptide macromolecules produced supramolecular vesicle-like nanostructures with aqueous colloidal stability suitable as nanocarriers for passive and active targeting of cancer tumors. The optical properties and physicochemical features of the nanoconjugates confirmed their suitability as photoluminescent nanoprobes for cell bioimaging and intracellular tracking. Moreover, the results in vitro demonstrated a notable killing activity towards GBM cells of cysteine-bearing CMC conjugates coupled with pro-apoptotic KLA peptides. More importantly, compared to doxorubicin (DOX), a model anticancer drug in chemotherapy that is highly toxic, these innovative nanohybrids nanoconjugates displayed higher lethality against U-87 MG cancer cells. In vivo CAM assays validated these findings where the nanohybrids demonstrated a significant reduction of GBM tumor progression (41% area) and evidenced an antiangiogenic activity. These results pave the way for developing polymer-based hybrid nanoarchitectonics applied as targeted multifunctional theranostics for simultaneous imaging and therapy against glioblastoma while possibly reducing the systemic toxicity and side-effects of conventional anticancer chemotherapeutic agents.

Polysaccharide based Copolymers as Supramolecular Systems in Biomedical Applications.

Polysaccharides are natural polymers, obtained from a large variety of sources ranging from fungi to more complex organisms such as birds and whales. Their use for pharmaceutical and biomedical applications has been the subject of numerous researches by the world´s academia. Polysaccharide chemical/physical modifications leading to graft copolymers are discussed in this review, focusing on those nanosystems that are potential candidates for drug delivery applications. Therefore, this review focuses on the biomedical application of polysaccharide based copolymers, particularly as nanocarriers. Copolymer of polysaccharides such as alginate, cellulose, chitosan, dextran, guar, hyaluronic acid, pullulan and starch as drug delivery nanocarriers will be discussed.