BackgroundNanocarrier-based systems have cultivated significant improvements in prostate cancer therapy. However, the efforts are still limited in clinical applicability, and more research is required for the development of effective strategies. Here, we describe a novel nanoliposomal system for targeted apoptotic gene delivery to prostate cancer.MethodsPoly (2-ethyl-2-oxazoline) (PEtOx) dioleoyl phosphatidylethanolamine (DOPE) nanoliposomes were conjugated with the prostate-specific membrane antigen (PSMA)-targeting peptide GRFLTGGTGRLLRIS (P563) and loaded with BikDDA, a mutant form of the proapoptotik Bik. We selected 22Rv1 cells with moderate upregulation of PSMA to test the in vitro uptake, cell death, and in vivo anti-cancer activity of our formulation, P563-PEtOx-DOPE-BikDDA.ResultsBikDDA was upregulated in 22Rv1 cells, inducing cell death, and CD-1 nude mice xenografts administered with the formulation showed significant tumor regression.ConclusionWe suggest that P563-PEtOx-DOPE-BikDDA nanoliposomes can serve as prominent gene carriers against prostate cancer.

Transglutaminase 2 (TG2) is a multifunctional crosslinking enzyme that displays transamidation, protein disulfide isomerase, protein kinase, as well as GTPase and ATPase activities. TG2 can also act as an adhesion molecule involved in the syndecan and integrin receptor signaling. In recent years, TG2 was implicated in cancer progression, survival, invasion, migration, and stemness of many cancer types, including renal cell carcinoma (RCC). Von Hippel-Lindau mutations leading to the subsequent activation of Hypoxia Inducible Factor (HIF)-1-mediated signaling pathways, survival signaling via the PI3K/Akt pathway resulting in Epithelial Mesenchymal Transition (EMT) metastasis and angiogenesis are the main factors in RCC progression. A number of studies have shown that TG2 was important in HIF-1- and PI3K-mediated signaling, VHL and p53 stabilization, glycolytic metabolism and migratory phenotype in RCC. This review focuses on the role of TG2 in the regulation of molecular pathways nurturing not only the development and propagation of RCC, but also drug-resistance and metastatic potential.