•A GO-C60 hybrid was constructed by stepwise conjugation.•GO-C60 exhibits good solubility and colloidal stability in physiological solutions.•GO-C60 generates reactive oxygen species under green, red and NIR light.•GO-C60 exhibits considerable temperature variations upon irradiation of NIR light.•GO-C60 shows combined effects of photodynamic therapy and photothermal therapy.Photodynamic therapy (PDT) and photothermal therapy (PTT) are two promising methodologies for cancer therapy. Although a variety of materials which can be used in PDT and PTT have been developed in the past decades, those showing the combined effect of PDT and PTT under NIR irradiation are rare. Graphene oxide (GO) and fullerene C60 (denoted as C60 hereafter) with unique physical and chemical properties are promising candidates for PTT and PDT, respectively. Here, by using a stepwise conjugation method, a new GO-C60 hybrid which contains hydrophilic methoxypolyethylene glycol (mPEG) and mono-substituted C60 was constructed for combined PDT and PTT. The hybrid shows good solubility in different environments including physiological solutions. The introduction of C60 to GO did not decrease the photothermal properties of GO, while the conjugation of GO to C60 activated the ability of C60 to generate singlet oxygen (1O2) in near infrared (NIR) region in aqueous solution. The GO-C60 hybrid also shows good ability to induce the generation of reactive oxygen species (ROS) in Hela cells. Due to the synergistic effect between GO and C60, GO-C60 hybrid exhibits superior performance in the inhibition of cancer cells compared to both individuals, indicating its high potential in practical applications.

•Centrifugation can separate nanoparticles with low ζ potential into different sizes.•Transport and uptake of OAE polysaccharide nanoparticles were size dependent.•Endocytic mechanisms of OAE nanoparticles were size dependent.Four batches of oleoyl alginate ester (OAE) nanoparticles with narrow size distribution were rapidly separated from the initial batch of nanoparticles by means of centrifugation at the relative centrifugal force (RCF) between 270 × g and 6750 × g after adjusting the zeta potential. The size of nanoparticles decreased with increasing speed of centrifugation, and the polydispersity of nanoparticles significantly decreased. As particle size increased the loading capacity also increased, while transport across Caco-2 cells and the cellular uptake of nanoparticles in jejunum decreased. Endocytosis of nanoparticles around 50 nm/120 nm, 420 nm and 730 nm occur mainly via clathrin-mediated endocytosis, caveolae-mediated endocytosis and macropinocytosis respectively. These results show that centrifugation could separate nanoparticles with appropriate zeta potential into different sizes and the transport and cellular uptake of OAE polysaccharide nanoparticles were size dependent.

Histidine–hyaluronic acid (His–HA) conjugates were synthesized using hyaluronic acid (HA) as a hydrophilic segment and histidine (His) as hydrophobic segment by 1-ethyl-3(3-dimethylaminopropyl)carbodiimide (EDC) mediated coupling reactions. The structural characteristics of the His–HA conjugates were investigated using 1H NMR. His–HA nanoparticles (HH-NPs) were prepared based on His–HA conjugates, and the characteristics of HH-NPs were investigated using dynamic light scattering, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and fluorescence spectroscopy. The particles were between 342 and 732 nm in size, depending on the degree of substitution (DS) of the His. TEM and SEM images indicated that the morphology of HH-NPs was spherical in shape. The critical aggregation concentrations of HH-NPs ranged from 0.034 to 0.125 mg/ml, which decreased with an increase in the DS of the His. Images of fluorescence microscopy indicate that HH-NPs were taken up by the cancer cell line (MCF-7), and significantly decreased by competition inhibition of free HA. From the cytotoxicity test, it was found that DOX-loaded HH-NPs exhibited similar dose and time-dependent cytotoxicity against MCF-7 cells with free DOX.

Hydrophobic alginate derivative was prepared by modification of alginate by acid chloride reaction using oleoyl chloride without organic solvents. The conjugate of oleoyl alginate ester (OAE) was confirmed by FT-IR and 1H NMR. The degree of substitution (DS) of OAE was determined by 1H NMR, and it ranged from 0.84 to 3.85. In distilled water, OAE formed self-assembled nanoparticles at low concentrations in aqueous medium, and nanoparticles retained their structural integrity both in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The loading and release characteristics of nanoparticles based on OAE were investigated using vitamin D3 as a model nutraceutical. As the concentration of vitamin D3 increased, the loading capacity (LC) increased, whereas the loading efficiency (LE) decreased. Nanoparticles could release vitamin D3 at a sustained rate in gastrointestinal fluid. These results revealed the potential of OAE nanoparticles as oral carriers for sustained release of vitamin D3.

Folate (FA) modified carboxymethyl chitosan (FCC) has been synthesized and the hydrogel nanoparticles can be prepared after the sonication. Formation and characteristics of nanoparticles of FCC were studied by fluorescence spectroscopy and dynamic light scattering methods. The critical aggregation concentration value of FCC in water was 9.34 × 10−2 mg/ml and the mean hydrodynamic diameter of particle was 267.8 nm. The morphology of nanoparticles was observed by transmission electron microscopy which had spherical shape. Loading capacity (LC), loading efficiency (LE) and the in vitro release profiles of nanoparticles were investigated by doxorubicin (DOX) as a model drug. When the initially added amount of DOX versus the constant amount of FCC polymer was increased, the LC in the nanoparticles was gradually increased and the LE decreased. The in vitro release profile of the DOX from the FCC nanoparticles exhibited sustained release. Cellular uptake of FCC nanoparticles was found to be higher than that of nanoparticles based on linoleic acid (LA) modified carboxymethyl chitosan because of the FA-receptor-mediated endocytosis, thereby providing higher cytotoxicity against Hela cells.

The purpose of the present research work was to study the formation of linoleic acid (LA) modified carboxymethyl chitosan (LCC). Another objective was to evaluate effect of linoleic acid degree of substitution on loading capacity (LC), ADR loading efficiency (LE) and in vitro release profile of LCC nanoparticles. The hydrogel nanoparticles can be prepared using linoleic acid modified carboxymethyl chitosan (LACMCS) after the sonication. The critical aggregation concentration (CAC) of the self-aggregate of LA modified CMCS (LCC) was determined by measuring the fluorescence intensity of the pyrene as a fluorescent probe. The CAC values were in the range of 0.061–0.081 mg/mL. Self-aggregated nanoparticles exhibited an increased LC and LE, decreased sustained release with an increasing ratio of the hydrophobic LA to hydrophilic CMCS. LCC nanoparticles loaded with ADR exerted in vitro anticancer activity against Hela cells that was comparable to the activity of free (non-entrapped in nanoparticles) ADR.