Self-assembled Camptothecin derivatives - Curcuminoids conjugate for combinatorial chemo-photodynamic therapy to enhance anti-tumor efficacy.

Camptothecin (CPT), an alkaloid, was first discovered from plants and has potent anti-tumor activity. Since then, CPT analogs (namely Irinotecan and Topotecan) have been approved by the FDA for cancer treatments. Curcumin, on the other hand, is a widely used photosensitizer in photodynamic therapy (PDT) treatment. In our previous work, we have reported a straightforward strategy to construct a drug self-delivery system in which two-molecular species Irinotecan and Curcumin can self-assembly into a complex of ion pairs, namely ICN, through intermolecular non-covalent interactions. We found that ICN has slightly better chemotherapy efficacy than its individual components with much fewer side effects. In this paper, we aim to combine the chemotherapy and the PDT of ICN to further improve its anti-tumor performance. The efficient cellular uptake of ICNs was observed by confocal microscopy. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay was used to detect the generation of singlet oxygen species. We found that the cell viability was 9% with both chemotherapy and PDT, and 31% with chemotherapy alone for the case with an ICN concentration of 10 µM, which demonstrated that the anti-tumor efficacy against the HT-29 cancer cell line was enhanced substantially with the combination therapy strategy. The study with an in vivo mouse model has further verified that the chemo-PDT dual therapy can inhibit tumor growth by 84% and 18.8% comparing with the control group and the chemotherapy group, respectively. Our results demonstrated that the new strategy using self-assembly and carrier-free nanoparticles with their chemo-PDT dual therapy may provide new opportunities to develop future combinatorial therapy methods in treating cancer.

The interplay of extracellular polymeric substances and oil/Corexit to affect the petroleum incorporation into sinking marine oil snow in four mesocosms.

Large amounts of oil containing mucous-like marine snow formed in surface waters adjacent to the Deepwater Horizon spill that was implicated in oil delivery to the seafloor. However, whether chemical dispersants that were used increased or decreased the oil incorporation and sedimentation efficiency, and how exopolymeric substances (EPS) are involved in this process remains unresolved. To investigate the microbial responses to oil and dispersants in different oceanic settings, indicated by EPS production, petro- and non-petro carbon sedimentation, four mesocosm (M) experiments were conducted: 1) nearshore seawater with a natural microbial consortia (M2); 2) offshore seawater with f/20 nutrients (M3); 3) coastal seawater with f/20 nutrients (M4); 4) nearshore seawater with a natural microbial consortia for a longer duration (M5). Four treatments were conducted in M2, M3 and M4 whereas only three in M5: 1) a water accommodated fraction of oil (WAF), 2) a chemically-enhanced WAF prepared with Corexit (CEWAF, not in M5), 3) a 10-fold diluted CEWAF (DCEWAF); and 4) controls. Overall, oil and dispersants input, nutrient and microbial biomass addition enhanced EPS production. Dispersant addition tended to induce the production of EPS with higher protein/carbohydrate (P/C) ratios, irrespective of oceanic regions. EPS produced in M4 was generally more hydrophobic than that produced in M3. The P/C ratio of EPS in both the aggregate and the colloidal fraction was a key factor that regulated oil contribution to sinking aggregates, based on the close correlation with %petro-carbon in these fractions. In the short term (4-5 days), both the petro and non-petro carbon sedimentation efficiencies showed decreasing trends when oil/dispersants were present. In comparison, in the longer-term (16 days), petro-carbon sedimentation efficiency was less influenced by dispersants, possibly due to biological and physicochemical changes of the components of the oil-EPS-mineral phase system, which cooperatively controlled the sinking velocities of the aggregates.

Impact of exposure of crude oil and dispersant (Corexit) on aggregation of extracellular polymeric substances.

Spilled oil treated with Corexit dispersant can cause unintended impacts on marine environment systems including altering marine organic matter dynamics; however, impacts on microgels and marine oil snow (MOS) formation are still debated and remain to be fully understood. Extracellular polymeric substances (EPS) are a major source of marine organic carbon for MOS and microgel formation. EPS initial aggregation plays key roles in the oil degrading process and various biogeochemical reactions. Here we used four types of EPS with water accommodated fraction (WAF), chemically-enhanced WAF (CEWAF) and Corexit, to represent potential situations during oil spills and post-application of Corexit. We found that Corexit alone can inhibit EPS aggregation and disperse pre-existing microgels. CEWAF can enhance EPS aggregation with efficiency by up to 80%-100% and more aggregates accumulated within the air-water interface. Additionally, more hydrophobic EPS aggregates showed high resistance to Corexit dispersion while hydrophilic EPS were more sensitive. Effects of oil spills on marine gel particle formation are primarily determined by chemical characteristics (hydrophobicity and protein content) of the constituent EPS. This study offers unique insights for organic particle dynamics and identifies controlling factors for MOS or gel particles associated with oil spills and Corexit dispersant used.

Superhydrophobic graphene-based sponge as a novel sorbent for crude oil removal under various environmental conditions.

Mechanical recovery of oils using oil sorbents is one of the most important approaches to manage marine oil spills. However, the properties of the oils spilled into sea are influenced by external environmental conditions. In this study, we present a graphene-based (GB) sponge as a novel sorbent for crude oil removal and compare its performance with that of a commercial sorbent sheet under various environmental parameters. The GB sponge with excellent superhydrophobic and superoleophilic characteristics is demonstrated to be an efficient sorbent for crude oils, with high sorption capacity (up to 85-95 times its weight) and good reusability. The crude-oil-sorption capacity of our GB sponge is remarkably higher (about 4-5 times) than that of the commercial sheet and most other previously reported sponge sorbents. Moreover, several challenging environmental conditions were examined for their effects on the sorption performance, including the weathering time of oils, seawater temperature, and turbulence (wave effect). The results show that the viscosity of the oil increased with increasing weathering time or decreasing temperature; therefore, the sorption rate seemed to decrease with longer weathering times and lower temperatures. Turbulence can facilitate inner sorption and promote higher oil sorption. Our results indicate that the extent of the effects of weather and other environmental factors on crude oil should be considered in the assessment of the effective adsorption capacity and efficiency of sorbents. The present work also highlights the widespread potential applications of our GB sponge in marine spilled-oil cleanup and hydrophobic solvent removal.

Corexit, oil and marine microgels.

Corexit, an EPA-approved chemical dispersant, was intensively used during the 2010 Deepwater Horizon Oil Spill in the Gulf of Mexico. Current studies surrounding Corexit have mainly focused on its toxicity and oil removal capacity. The potential impact of Corexit on the surface ocean carbon dynamics has remained largely unknown. The spontaneous assembly of DOM (dissolved organic matter) polymers into microgels (POM, particulate organic matter) was demonstrated previously that it can influence various critical processes, such as colloidal pump, microbial loops, and nutrition availability in the surface ocean. Here, we report that Corexit alone can significantly inhibit DOM microgel formation and reduce the stability of pre-existing microgels. However, Corexit and oil, Chemically Enhanced Water Accommodated Fraction (CEWAF), could effectively facilitate DOM microgel formation. The unanticipated disturbance of Corexit and oil spills on the critical DOM-POM continuum warrant particular caution and thus should be considered for future application of Corexit during oil spills.