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Although noticeable scientific and technological progress, cancer remains one of the deadliest diseases worldwide and advancements in diagnosis, targeting and treating cancer cells are an urgency. In this study, we designed and synthesized novel amino acid and polypeptide modified polysaccharide derivatives associated with fluorescent nanomaterials for producing nanohybrids with functionalities for bioimaging and cell penetrating. Carboxymethylcellulose (CMCel) was chemically biofunctionalized with L-cysteine (CMCelCys) or poly-L-arginine (CMCelPolyArg) and the conjugates were used as capping ligands for synthesizing fluorescent AgInS 2 quantum dots (AIS-QDs) in aqueous colloidal media. These systems were characterized by FTIR, NMR, UV–Vis, TEM-EDX, DLS, zeta potential and PL for assessing physicochemical properties, structural and morphological features. Mitochondrial activity assay (MTT) was used for evaluating preliminary cytotoxicity and confocal laser microscopy for investigating cellular uptake of the nanohybrids. Results confirmed the biofunctionalization of CMCel through amide bonds formation and indicated the formation of water-dispersed fluorescent nanocolloids with core-shell nanostructures composed by semiconductor cores stabilized by shell layers of CMCelCys or CMCelPolyArg. The nanohybrids' optical properties were affected by the grafting of functionalities into CMCel. All nanohybrids demonstrated no in vitro cytotoxicity based on MTT results and were successfully internalized by glioma cells, behaving as fluorescent nanoprobes for bioimaging and biolabeling. Unlabelled Image • Novel "green" fluorescent polysaccharide-AIS QD nanobioconjugates were developed. • Core-shell nanostructures were functionalized with L-cysteine and poly-L-arginine. • AIS-carboxymethylcellulose colloids were formed and functionalized in aqueous media. • The nontoxic nanoconjugates behaved as active fluorescent nanoprobes for bioimaging. • The nanoconjugates can be applied as fluorescent nanoplatforms for cancer research. [ABSTRACT FROM AUTHOR]

In this study, it is reported the use of sodium carboxymethyl cellulose (CMCel) as a multifunctional biocompatible polysaccharide for the direct synthesis of fluorescent alloyed-ZnCdS quantum dot (QD) nanoconjugates via aqueous “green” process at room temperature. The nanoconjugates were extensively characterized by spectroscopical (NMR, FTIR, UV-vis, PL) and morphological techniques (DLS, TEM) for accessing their structural and physicochemical properties associated with X-ray photoelectron spectroscopy (XPS) for surface and interface analysis. The results proved the hypothesis of formation of core-shell nanostructures composed by the semiconductor ZnCdS QD core and the organic biocompatible ligand CMCel shell. Moreover, CMCel chemical functional groups played a pivotal role for controlling the size of water-soluble colloidal nanocrystals (2r = 4–5 nm) and hydrodynamic diameters (<15 nm) evidenced by metal complexation and interactions at the nanointerfaces. Additionally, these nanoconjugates were cytocompatible and luminescent for bioimaging human osteosarcoma cancer cells. Thus, these novel polysaccharide-based fluorescent bioconjugates offer promising perspectives as nanoplatforms for cancer cell bioimaging and diagnosis purposes. [ABSTRACT FROM AUTHOR]

Nanobiomaterials can be engineered to recognize cancer-specific receptors at the cellular level for diagnostic and therapeutic purposes. In this work, we report the synthesis of novel multifunctional nanoconjugates composed of fluorescent inorganic semiconductor quantum dot (QD) cores and tripeptide-modified polysaccharide organic shells. These structures were designed for targeting and imaging the α v β 3 integrin receptors of cancer cells. Initially, chitosan was covalently bound with the RGD peptide using a crosslinker to form bioconjugates (RGD-chitosan), which were later utilized as capping ligands for the production of surface-functionalized CdS QDs via a single-step process in aqueous media at room temperature. These core-shell nanostructures were extensively characterized by UV–vis spectroscopy, photoluminescence (PL) spectroscopy, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), zeta potential (ZP) and dynamic light scattering (DLS). The TEM images and the UV–vis absorption results indicated the formation of ultra-small CdS QD nanocrystals with average diameters between 2.0 and 3.0 nm. In addition, the PL results demonstrated that the nanobioconjugates exhibited intense green fluorescence under excitation. The CdS-RGD-chitosan systems were effective at specific targeting integrin when assayed in vitro using two model cell cultures, HEK 293 (non-cancerous human embryonic kidney cell) and SAOS (cancerous sarcoma osteogenic-derived cells) imaged using fluorescence microscopy. [ABSTRACT FROM AUTHOR]

Cancer remains one of the world's most devastating diseases with millions of fatalities and new cases every year. In this work, we attempted to develop a facile “enzyme-free” fluoroimmunoassay based on the novel nanoconjugates composed of CdS quantum dots (QDs) as the fluorescent inorganic core and an antibody-modified polysaccharide as the organic shell, modeling their possible application for the in vitro diagnosis of non-Hodgkin lymphoma (NHL) cancer. Chitosan was conjugated with an anti-CD20 polyclonal antibody (pAbCD20) by the formation of covalent amide bonds. In the sequence, these chitosan-antibody conjugates were utilized as direct ligands for the surface biofunctionalization of CdS QDs (CdS/chitosan-pAbCD20) using a single-step colloidal process in aqueous medium at room temperature. The most relevant physico-chemical properties of these nanoconjugates were assessed by morphological and spectroscopic techniques. The results indicated that CdS nanocrystals were produced with an average diameter of 2.5 nm and with cubic zinc blende crystalline nanostructure. The CdS-immunoconjugates (CdS/chitosan-pAbCD20) presented colloidal hydrodynamic diameter (H D ) of 15.0 ± 1.2 nm. In addition, the results evidenced that the “enzyme-free” QD-linked immunosorbent assay (QLISA) was effective for the in vitro detection against the antigen CD20 (aCD20) based on fluorescent behavior of the CdS nanoconjugates. Moreover, the CdS-immunoconjugates were successfully used for fluorescence bioimaging of NHL cancer cells. Finally, the cell viability results using different cell cultures based on LDH, MTT and Resazurin bio-assays have demonstrated no cytotoxicity of the new CdS-chitosan bioconjugates relative to the standard controls. Thus, CdS conjugates may offer a promising platform for the future development of in vitro and in vivo applications for the detection and diagnosis of NHL cancer cells. [ABSTRACT FROM AUTHOR]

Hybrid Core-Shell Nanostructures: Integrating Biofunctionalized Polysaccharide-Drug Conjugates with Fluorescent Semiconductor Nanocrystals against Cancer. • New biofunctional quantum dot/polysaccharide/folate nanoconjugates were produced. • Cu-In-S/ZnS-CMC core-shell hybrid conjugates produced by facile green aqueous process. • ZCIS-CMC conjugates acted as non-toxic optical nanoprobes for bioimaging cancer cells. • Cu-In-S/ZnS-CMC nanocolloids biofunctionalized by folate targeted breast cancer cells. • ZAIS-CMC-FA/DOX acted as targeted-drug delivery nanocarriers for killing cancer cells. Although the field of oncology nanomedicine has shown indisputable progress in recent years, cancer remains one of the most lethal diseases, where the early diagnosis plays a pivotal role in the patient's prognosis and therapy. Herein, we report for the first time, the synthesis of biocompatible nanostructures composed of Cu-In-S and Cu-In-S/ZnS nanoparticles functionalized with carboxymethylcellulose biopolymer produced by a green aqueous process. These inorganic-organic colloidal nanohybrids developed supramolecular architectures stabilized by chemical functional groups of the polysaccharide shell with the fluorescent semiconductor nanocrystal core, which were extensively characterized by several morphological and spectroscopical techniques. Moreover, these nanoconjugates were covalently bonded with folic acid via amide bonds and electrostatically conjugated with the anticancer drug, producing functionalized supramolecular nanostructures. They demonstrated nanotheranostics properties for bioimaging and drug delivery vectorization effective for killing breast cancer cells in vitro. These hybrids offer a new nanoplatform using fluorescent polysaccharide-drug conjugates for cancer theranostics applications. [ABSTRACT FROM AUTHOR]

Semiconductor quantum dots (QDs) are one of the most interesting photoluminescent nanomaterials with very promising applications in cancer nanomedicine. In this work, ZnS fluorescent quantum dots (ZnS-QDs) were synthesized and stabilized by carboxymethylcellulose (CMC) as a pH-sensitive biopolymer using a facile one-step green aqueous colloidal process at distinct pH conditions (acidic, neutral and alkaline) and chemical proportions of precursors (Zn2+, S2−). The optical properties of these nanoconjugates (ZnS@CMC) were characterized by UV–visible and photoluminescence spectroscopy. The morphological features and physicochemical properties were evaluated by TEM, FTIR spectroscopy, zeta potential, and dynamic light scattering (DLS) analyses. The cytocompatibility in vitro of ZnS@CMC was assessed by MTT assay using normal and malignant glioma cells. The UV–Vis results indicated that ZnS-QDs were effectively produced with different bandgap energies (from 4.5 to 3.8 eV) blue-shifted from bulk (E bulk = 3.61 eV), and sizes (typically from 3.3 to 4.5 nm), dependent on the pH and concentration ratio of precursors during the synthesis. Analogously, the changes of synthesis parameters significantly altered the photoluminescence emission energies and intensities within the visible range of spectra (PL maxima from λ = 400–430 nm, at pH = 3.5, [Zn:S] ratio = 1:2). The cell viability results in vitro (>90%) demonstrated no cytotoxicity of ZnS@CMC nanohybrids towards both cell types. Importantly, these ZnS@CMC nanoconjugates behaved as active fluorescent nanoprobes for bioimaging malignant glioma cells proving the high potential for applications in cancer nanomedicine. Image 1004 • Facile green synthesis of ZnS quantum dot-carboxymethylcellulose nanoconjugates. (79). • CMC pH-sensitive ligand tailored nucleation/growth processes of ZnS nanocrystals. (80). • Colloidal process parameters regulated the optical properties of ZnS@CMC nanohybrids. (84). • ZnS@CMC colloids behaved as active photoluminescent biological nanoprobes. (73). • Fluorescent nanoconjugates were effective for bioimaging brain cancer cells in vitro. (84). [ABSTRACT FROM AUTHOR]

• Facile green synthesis of ZnS quantum dot-carboxymethylcellulose-DOX nanoconjugates. (83) • New ZnS@CMC-DOX supramolecular nanohybrids were produced by a green colloidal process. (85) • ZnS@CMC-DOX bioconjugates behaved as photoluminescent bioprobes and drug nanocarriers. (85) • Nanocolloids were suitable for bioimaging and killing brain cancer cells in vitro. (81) Glioblastoma (GBM) is the utmost aggressive and lethal primary brain cancer, which has a poor prognosis and remains virtually incurable. Nanomedicine with emerging disruptive nanotechnology alternatives, including designed supramolecular nanohybrids has excellent potential as multimodal tools against cancer by combining nanomaterials, biomacromolecules, and drugs. Thus, we developed and constructed for the first time quantum dot-biopolymer-drug nanohybrids based on host-guest chemistry for simultaneous bioimaging, targeting, and anti-cancer drug delivery against GBM cells in vitro. ZnS fluorescent quantum dots (ZnS-QDs) were produced using chemically modified polysaccharide, carboxymethylcellulose (CMC), as water-soluble capping ligand and biofunctional layer via a facile one-step eco-friendly aqueous colloidal process at room temperature and physiological pH. These hybrid inorganic-organic nanocolloids (ZnS@CMC) were electrostatically conjugated with doxorubicin (DOX) anti-cancer drug forming innovative supramolecular complexes (ZnS@CMC-DOX) for amalgamating bioimaging and killing cancer cells. These nanoconjugates were characterized regarding their optical and physicochemical properties combined with morphological and structural features. The cytocompatibility was evaluated by MTT assay using healthy and GBM cells. The results showed that ultra-small ZnS-QDs were expertly produced uniform nanocolloids (average size = 3.6 nm). They demonstrated photoluminescence emission within the visible range of spectra. The cell viability results in vitro showed no cytotoxicity of ZnS@CMC nanohybrids towards both cell types. In summary, the novelty of this research relies on using a nanotheranostic strategy for developing ZnS@CMC-DOX nanohybrids with supramolecular vesicle-like structures. They behaved simultaneously as active fluorescent nanoprobes and nanocarriers with modulated drug release for bioimaging and killing malignant glioma cells proving the high potential for applications in cancer nanomedicine. [ABSTRACT FROM AUTHOR]

Novel core-shell superparamagnetic nanofluids composed of magnetic iron oxide (Fe 3 O 4 , MION) and cobalt-doped (Co x Fe 3-x O 4 , Co-MION) nanoparticles functionalized with carboxymethyl cellulose (CMC) ligands were designed and produced via green colloidal aqueous process. The effect of the degree of substitution (DS = 0.7 and 1.2) and molecular mass (M w) of CMC and cobalt doping concentration on the physicochemical and magnetic properties of these nanoconjugates were comprehensively investigated using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction, transmission electron microscopy (TEM) with selected area electron diffraction, X-ray fluorescence, dynamic light scattering (DLS), zeta potential (ZP) analysis, vibrating sample magnetometry (VSM) and electron paramagnetic resonance spectroscopy (EPR). The results demonstrated the effect of concentration of carboxylate groups and M w of CMC on the hydrodynamic dimension, zeta potential, and generated heat by magnetic hyperthermia of MION nanoconjugates. Co-doping of MION showed significant alteration of the electrostatic balance of charges of the nanoconjugates interpreted as effect of surface interactions. Moreover, the VSM and EPR results proved the superparamagnetic properties of these nanocolloids, which were affected by the presence of CMC and Co-doping of iron oxide nanoparticles. These magnetic nanohybrids behaved as nanoheaters for killing brain cancer cells in vitro with prospective future applications in oncology and nanomedicine. Magnetic iron oxide nanoparticles/carboxymethyl cellulose biopolymer – " Smart nanohybrids" for magneto-thermotherapy of cancer cells. Unlabelled Image • Carboxymethyl cellulose-magnetic iron oxide nanoparticle conjugates were synthesized. • CMC‑iron oxide (Fe 3 O 4) and Co-doped (Co x Fe 3-x O 4) nanocolloids were produced in water. • Degree of substitution and molar mass of CMC tuned properties of Fe 3 O 4 nanoconjugates. • Fe 3 O 4 and Co-doped nanoparticles showed distinct surface interactions with CMC groups. • New CMC-Fe 3 O 4 conjugates proved activity as nanoheaters to kill brain cancer cells. [ABSTRACT FROM AUTHOR]

An electrochemical approach has been used for the aqueous synthesis of low-toxicity and eco-friendly copper indium sulfide (CuInS 2) nanocrystals, and related core@shell systems (CuInS 2 @ZnX, where X = S2- and Se2-). The chalcogenide precursors (S2-, Se2-) were generated in electrochemical cavity cell, using a constant current electrolysis (i = 30 mA and Q = 11.5C), in the presence of metallic precursors (In3+, Cu+, Zn2+), room temperature and argon atmosphere. Firstly, In 2 S 3 seeds were obtained in the intermediate compartment of the cell and converted to CuInS 2 by thermoactivated diffusion (colloidal solution under reflux) of Cu+ ions into the In 2 S 3 lattice. Cu+/In3+ ratios = 0.25 and 0.125 were tested for the production of CuInS 2 stabilized by l -glutathione (GSH), and characterized by UV–vis and emission spectroscopy, XRD, HRTEM and zeta potential. CuInS 2 @ZnX nanoparticles were prepared by using the same electrochemical system, paired electrolysis and Zn sacrificial anode. Nanocrystals prepared under Cu+/In3+ = 0.125 reached 3.1% (CuInS 2), 4.6% (CuInS 2 @ZnSe), and 9.6% (CuInS 2 @ZnS) quantum yields. The CuInS 2 @ZnX systems presented high cell viability (85%–94%) and internalization in cytosol region of HeLa cells, showing high potential for biological labeling. Image 1 • Copper indium sulfide nanocrystals were synthesized by eco-friendly electrochemical method. • The covering of CuInS 2 nanocrystal with ZnS and ZnSe improves the quantum yield. • First report of CuInS 2 @ZnSe water synthesis text & application as nontoxic biomarker. • CuInS 2 @ZnX (X = S, Se) was shown to give 84–95% cell viability in cytosol HeLa cells. [ABSTRACT FROM AUTHOR]