title: Critical factors in the development of tumor-targeted anti-inflammatory nanomedicines.
abstract: Tumors are complex and dynamic assemblies of different cell types within an atypical/abnormal architecture. Tumor-associated macrophages, mast cells, dendritic cells, eosinophils, fibroblasts are present in and around tumors and contribute to an abundant, deregulated and long lasting chronic inflammation, a permissive microenvironment for tumor proliferation. The fact that tumor-initiated inflammation overrides protective immunity and supports tumor development, combined with the successful strategy of liposomal drug targeting to tumor tissues, gave rise to a novel attractive antitumor therapeutic strategy: targeting anti-inflammatory drugs to tumors. As many natural bioactive compounds have anti-inflammatory properties and act by targeting multiple signaling pathways, their medicinal application involves the treatment of cancer. The nanoformulation into liposomes circumvents solubility, stability, bioavailability issues associated with these compounds, while promoting tumor drug accumulation. Liposomal formulations of resveratrol, carvacrol phosphate, pterostilbene phosphate, N-(3-oxo-dodecanoyl)-l-Homoserine lactone, caffeic acid and caffeic acid phenethyl ester (CAPE) were prepared and characterized. In vivo, B16F10 melanoma bearing mice seem not to be responsive to liposomal treatments of natural compounds. The specific combination of tumor model, drug delivery system and drug potency are crucial factors that should be considered in the development and evaluation of new nanomedicines for cancer-inflammation therapy, especially when translating from preclinical models.
authors: Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Dept. of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors: Maria
authors: M
authors: Coimbra
authors: Bart J
authors: BJ
authors: Crielaard
authors: Gert
authors: G
authors: Storm
authors: Raymond M
authors: RM
authors: Schiffelers
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004354:Drug Screening Assays, Antitumor; D008081:Liposomes; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry*; D009368:Neoplasm Transplantation; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes