title: Use of Nanotechnology to Develop Multi-Drug Inhibitors For Cancer Therapy.
abstract: Therapeutic agents that inhibit a single target often cannot combat a multifactorial disease such as cancer. Thus, multi-target inhibitors (MTIs) are needed to circumvent complications such as the development of resistance. There are two predominant types of MTIs, (a) single drug inhibitor (SDIs) that affect multiple pathways simultaneously, and (b) combinatorial agents or multi-drug inhibitors (MDIs) that inhibit multiple pathways. Single agent multi-target kinase inhibitors are amongst the most prominent class of compounds belonging to the former, whereas the latter includes many different classes of combinatorial agents that have been used to achieve synergistic efficacy against cancer. Safe delivery and accumulation at the tumor site is of paramount importance for MTIs because inhibition of multiple key signaling pathways has the potential to lead to systemic toxicity. For this reason, the development of drug delivery mechanisms using nanotechnology is preferable in order to ensure that the MDIs accumulate in the tumor vasculature, thereby increasing efficacy and minimizing off-target and systemic side effects. This review will discuss how nanotechnology can be used for the development of MTIs for cancer therapy and also it concludes with a discussion of the future of nanoparticle-based MTIs as well as the continuing obstacles being faced during the development of these unique agents.'
authors.affiliation: Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA ; Penn State Hershey Melanoma Center, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA ; Penn State Melanoma Therapeutics Program, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA ; The Foreman Foundation for Melanoma Research, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Raghavendra
authors.initials: R
authors.lastname: Gowda
authors.affiliation: Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Jones
authors.affiliation: Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA ; Penn State Hershey Melanoma Center, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA ; Penn State Melanoma Therapeutics Program, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Shubhadeep
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA ; Department of Pathology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA ; Department of Dermatology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA ; Department of Surgery, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA ; Penn State Hershey Melanoma Center, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA ; Penn State Melanoma Therapeutics Program, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA ; The Foreman Foundation for Melanoma Research, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Robertson
keywords: Cancer therapy; Multi-drug inhibitors; Multi-target inhibitors; Nanoliposomes; Nanotechnology