RESUMO
A large number of experimental and clinical data indicates that tumor-associated macrophages (TAMs) were involved in the whole process of tumor growth, invasion and metastasis. Like macrophages in other tissues, TAMs originate from blood monocytes, which are recruited to the tumor tissues by cytokines and then differentiated into TAMs. It is interesting that the monocytes overexpress siglec receptor in their surface, which has a high binding specificity to sialic acid (SA). From this point of view, we hypothesize that if SA was used as a ligand in the surfaces of drug delivery systems, SA would enhance the targeting efficiency to monocytes, and thus to achieve a higher specificity to TAMs. In our previous study, an SA derivative of SA-octadecylamine (SA-18) was synthesized and was found to enhance cytotoxicity on TAMs in vitro. The chain length is a critical factor for SA efficiency in liposomes and it has a significant influence on the TAM targeting effects of the carriers. So in this study, four kinds of different chain length of SA fatty amine derivatives were synthesized, including SA-18, SA-hexadecylamine (SA-16), SA-tetradecylamine (SA-14) and SA-dodecylamine (SA-12), and were modified on the surfaces of blank liposomes (BLK-SnL, n=18, 16, 14, 12) and pixantrone maleate-loaded liposomes (Pix-SnL, n=18, 16, 14, 12). TAM targeting effects of these SA derivatives were evaluated by acute toxicity and antitumor efficacy in vivo. The results of acute toxicity experiments showed that the toxicities of the SA derivatives deceased gradually with the reduction in the length of lipophilic chain. The in vivo antitumor efficacies of SA-modified blank liposomes showed that these blank formulations had no effect on the tumor inhibition except BLK-S14L (61.4%±18.8%), and BLK-S16L even promoted the tumor growth (-31.7%±13.1%, the 18th day). The in vivo antitumor efficacies of SA-modified Pix liposomes showed that the tumor inhibition effects were Pix-S18L (97.4%±2.1%) > Pix-S14L (73.1%±21.1%) > Pix-S12L (53.9%±17.8%) > Pix-S16L (32.9%). Because of the relatively strong binding ability of SA-18, it was hard to fall off from the liposomes in the transport process, leading to a good TAM targeting ability and less toxicity to the normal tissues. Meanwhile, 50% of the mice in Pix-S18L group showed "tumor shedding" and "wound healing" phenomena without recurrence in two months following the treatment. Therefore, SA-18 is the most potential TAM targeting material among these SA fatty amine derivatives.
RESUMO
A laboratory-scale anaerobic baffled reactor (ABR) with four compartments using soybean protein processing wastewater as organic loading rates (OLRs) was investigated for the performance and phase separated characteristics. It was found that the chemical oxygen demand (COD) removal efficiencies were 92-97% at 1.2-6.0kgCOD/m3d feeding. The dominated species, propionate and butyrate, were found in the 1st compartment. Acetate was dominated in the 2nd compartment and then decreased in the 3rd and 4th. Meanwhile, 93% volatile fatty acids (VFAs) were removed in the 3rd and 4th compartments. In the 1st compartment, biogas revealed carbon dioxide (CO2) and hydrogen (H2). The highest H2 yield was found in the 2nd compartment, thereafter decreased from the 2nd to 4th which corresponded to the increased of the methane (CH4) yield. It indicated that the proper anaerobic consortium in each separate compartment was developed along with substrate availability and specific environmental conditions.
