Carbon nanomaterials such as multiwalled carbon nanotubes (MWCNTs) and graphene oxide (GO) have been functionalized by highly hydrophilic and biocompatible poly(vinyl alcohol) (PVA) for loading and delivery of an anticancer drug, camptothecin (CPT). For the first time, CPT was loaded onto MWCNT-PVA and GO-PVA through π-π interactions and its capability to kill human breast and skin cancer cells was investigated.

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In this research, we have covalently functionalized graphene oxide (GO) with hydrophilic and biocompatible Pluronic F38 (F38), Tween 80 (T80) and maltodextrin (MD) for loading and delivery of a poorly water soluble antioxidant and anticancer drug, ellagic acid (EA). The functionalized GO showed a good aqueous solubility and biocompatibility. This is the first time that the EA was loaded onto GO-F38, GO-T80 and GO-MD through π-π interactions, yielding a loading capacity of 1 g, 1.22 g and 1.14 g of EA per gram of GO-F38, GO-T80, and GO-MD respectively. Their capabilities to kill human breast carcinoma cells (MCF7) and human colon adenocarcinoma cells (HT29) were then investigated. The release of EA from these nanocarriers was studied in water (neutral pH) and buffer solutions of pH 4 and 10 at 37 ° C. The GO-F38, GO-T80 and GO-MD released ˜ 36-38% drug within 3 days at pH 10. The cytotoxicity of EA loaded onto the functionalized GO was higher than that of free EA dissolved in DMSO. The DPPH assay was used to study the antioxidant activity, and the very similar antioxidant activities were obtained for three EA-loaded nanocarriers and the free EA, indicating that loading of EA onto the functionalized GO did not hamper its antioxidant activity. Therefore, all three functionalized GOs are suitable nanocarriers for drug delivery because of their non-toxicity and high drug loading capacity.

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Formulated forms of cancer therapeutics enhance the efficacy of treatment by more precise targeting, increased bioavailability of drugs, and an aptitude of some delivery systems to overcome multiple drug resistance of tumors. Drug carriers acquire importance for anti-cancer interventions via targeting tumor-associated macrophages with active molecules capable to either eliminate them or change their polarity. Although several packaged drug forms have reached the market, there is still a high demand for novel carrier systems to hurdle limitations of existing drugs on active molecules, toxicity, bioeffect, and stability. Here, we report a facile assembly and delivery methodology for biodegradable polymeric multilayer capsules (PMC) with the purpose of further use in injectable drug formulations for lung cancer therapy via direct erosion of tumors and suppression of the tumor-promoting function of macrophages in the tumor microenvironment. We demonstrate delivery of low-molecular-weight drug molecules to lung cancer cells and macrophages and provide details on in vivo distribution, cellular uptake, and disintegration of the developed PMC. Poly-l-arginine and dextran sulfate alternately adsorb on a ∼500 nm CaCO3 sacrificial template followed by removal of the inorganic core to obtain hollow capsules for consequent loading with drug molecules, gemcitabine or clodronate. The capsules further compacted upon loading down to ∼250 nm in diameter via heat treatment. A comparative study of the capsule internalization rate in vitro and in vivo reveals the benefits of a diminished carrier size. We show that macrophages and epithelial cells of the lungs and liver internalize capsules with efficacy higher than 75%. Using an in vivo mouse model of lung cancer, we also confirm that tumor lungs better retain smaller capsules than the healthy lung tissue. The pronounced cytotoxic effect of the encapsulated gemcitabine on lung cancer cells and the ability of the encapsulated clodronate to block the tumor-promoting function of macrophages prove the efficacy of the developed capsule loading method in vitro. Our study taken as a whole demonstrates the great potential of the developed PMC for in vivo treatment of cancer via transporting active molecules, including those that are water-soluble with low molecular weight, to both cancer cells and macrophages through the bloodstream.