title: Nanodiamonds: The intersection of nanotechnology, drug development, and personalized medicine.
abstract: The implementation of nanomedicine in cellular, preclinical, and clinical studies has led to exciting advances ranging from fundamental to translational, particularly in the field of cancer. Many of the current barriers in cancer treatment are being successfully addressed using nanotechnology-modified compounds. These barriers include drug resistance leading to suboptimal intratumoral retention, poor circulation times resulting in decreased efficacy, and off-target toxicity, among others. The first clinical nanomedicine advances to overcome these issues were based on monotherapy, where small-molecule and nucleic acid delivery demonstrated substantial improvements over unmodified drug administration. Recent preclinical studies have shown that combination nanotherapies, composed of either multiple classes of nanomaterials or a single nanoplatform functionalized with several therapeutic agents, can image and treat tumors with improved efficacy over single-compound delivery. Among the many promising nanomaterials that are being developed, nanodiamonds have received increasing attention because of the unique chemical-mechanical properties on their faceted surfaces. More recently, nanodiamond-based drug delivery has been included in the rational and systematic design of optimal therapeutic combinations using an implicitly de-risked drug development platform technology, termed Phenotypic Personalized Medicine-Drug Development (PPM-DD). The application of PPM-DD to rapidly identify globally optimized drug combinations successfully addressed a pervasive challenge confronting all aspects of drug development, both nano and non-nano. This review will examine various nanomaterials and the use of PPM-DD to optimize the efficacy and safety of current and future cancer treatment. How this platform can accelerate combinatorial nanomedicine and the broader pharmaceutical industry toward unprecedented clinical impact will also be discussed.
authors.affiliation: Division of Oral Biology and Medicine, University of California, Los Angeles (UCLA) School of Dentistry, Los Angeles, CA 90095, USA. ; Department of Bioengineering, UCLA School of Engineering and Applied Science, Los Angeles, CA 90095, USA. ; The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, Los Angeles, CA 90095, USA. ; California NanoSystems Institute, UCLA, Los Angeles, CA 90095, USA. ; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Dean
authors.initials: D
authors.lastname: Ho
authors.affiliation: BRIM Biotechnology Inc., Taipei 11560, Taiwan, R.O.C.
authors.forename: Chung-Huei Katherine
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore. ; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 177599, Singapore. ; National University Cancer Institute, Singapore, Singapore 119082, Singapore.
authors.forename: Edward Kai-Hua
authors.initials: EK
authors.lastname: Chow
keywords: Drug Development; Nanoscience; combination therapy; nanodiamond; nanomedicine; personalized medicine; phenotype; precision medicine