Anticancer Activity of Water-Soluble Olsalazine-PAMAM-Dendrimer-Salicylic Acid-Conjugates

Improving the activity and selectivity profile of anticancer agents will require designing drug carrier systems that employ soluble macromolecules. Olsalazine-PAMAM-dendrimer-salicylic acid-conjugates with dendritic arms of different lengths have shown good stability regarding the chemical link between drug and spacer. In this study, the drug release was followed in vitro by ultraviolet (UV) studies. Evaluation of the cytotoxicity of the olsalazine-PAMAM-dendrimer-salicylic acid-conjugates employing a sulforhodamine B (SRB) assay in PC-3 (human prostatic adenocarcinoma) and MCF-7 (human mammary adenocarcinoma) cell lines demonstrated that conjugate 9 was more active as an antiproliferative agent than cisplatin, and no cytotoxicity towards the African green monkey kidney fibroblast (COS-7) cell line was observed in any of the conjugates synthesized in the present work.

Liposomal Taro Lectin Nanocapsules Control Human Glioblastoma and Mammary Adenocarcinoma Cell Proliferation

The search for natural anticancer agents and nanocarrier uses are a part of the current strategies to overcome the side effects caused by chemotherapeutics. Liposomal nanocapsules loaded with purified tarin, a potential immunomodulatory and antitumoral lectin found in taro corms, were produced. Liposomes were composed by 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine, cholesterylhemisuccinate, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[folate(polyethylene glycol)-2000 prepared by thin-film hydration. Small unilamellar vesicles were achieved by sonication and extrusion. Scanning electron microscopy evidenced round-shaped nanocapsules presenting a smooth surface, 150 nm diameter and polydispersity index <0.2, estimated by dynamic light scattering. Tarin entrapment rates were over 80% and leakage of ~3% under 40 days of storage at 4 °C. Entrapped tarin exhibited an 83% release after 6 h at pH 4.6–7.4 and 36 °C. Both free and encapsulated tarin exhibited no in vitro toxicity against healthy mice bone marrow and L929 cells but stimulated the production of fibroblast-like and large round-shaped cells. Encapsulated tarin resulted in inhibition of human glioblastoma (U-87 MG) and breast adenocarcinoma (MDA-MB-231) proliferation, with an IC50 of 39.36 and 71.38 µg/mL, respectively. The effectiveness of encapsulated tarin was similar to conventional chemotherapy drugs, such as cisplatin and temozolide. Tarin liposomal nanocapsules exhibited superior pharmacological activity compared to free tarin as a potential chemotherapy adjuvant.

T/Tn immunotherapy avoiding immune deviation

Tumor immunotherapy, capable of inducing both cellular and humoral immune responses, is an attractive treatment strategy for cancer. It has been reported that the inactivation of cell-mediated immunity by hyper-activation of humoral immunity—referred to as immune deviation—does not inhibit tumor growth. We investigated the ability of several adjuvants to elicit Thomsen-Friedenreich (T/Tn)-specific humoral immunity while avoiding immune deviation and conferring protection against tumorigenesis. T/Tn (9:1) antigen was purified from blood type O erythrocytes donated by healthy Korean volunteers. Immunization was performed using T/Tn only, T/Tn mixed with Freund’s adjuvant (T/Tn+FA), keyhole limpet hemocyanin (KLH)-conjugated T/Tn mixed with FA (KLH-T/Tn+FA), or oxidized mannan-conjugated T/Tn mixed with FA (ox-M-T/Tn+FA). Anti-T/Tn antibodies were generated in the T/Tn+FA, KLH-T/Tn+FA, and ox-M-T/Tn+FA groups. The antibody level was highest in the KLH-T/Tn+FA group. Mice immunized with ox-M-T/Tn+FA showed specific complement-dependent cytotoxicity, and were protected against T/Tn-positive mammary adenocarcinoma cell challenge, although anti-T/Tn antibody levels were the highest in the KLH-T/Tn+FA group. These results demonstrate that an ox-M-conjugated T/Tn vaccine mixed with FA can promote cellular immunity while moderating the humoral immune response, thereby effectively inhibiting tumor growth.