Drug Design, Development and Therapy (Oct 2019)
Smart Targeting To Improve Cancer Therapeutics
Abstract
Moraima Morales-Cruz,1,* Yamixa Delgado,2,* Betzaida Castillo,3 Cindy M Figueroa,4 Anna M Molina,1 Anamaris Torres,2 Melissa Milián,2 Kai Griebenow1,* 1Department of Chemistry, University of Puerto Rico, Río Piedras Campus, San Juan, PR, USA; 2Department of Biochemistry & Pharmacology, San Juan Bautista School of Medicine, Caguas, PR, USA; 3Department of Chemistry, University of Puerto Rico, Humacao Campus, Humacao, PR, USA; 4Department of Math and Sciences, Polytechnic University of Puerto Rico, San Juan, PR, USA*These authors contributed equally to this workCorrespondence: Yamixa Delgado PO Box 4968 Caguas, PR 00726-4968, USATel +1 787 743 3038Fax +1 787 746 3093Email [email protected] Kai Griebenow 17 Ave Universidad STE 1701, San Juan, PR 00925-2537, USATel +1 787 764 0000Fax +1 787 746 3093Email [email protected]: Cancer is the second largest cause of death worldwide with the number of new cancer cases predicted to grow significantly in the next decades. Biotechnology and medicine can and should work hand-in-hand to improve cancer diagnosis and treatment efficacy. However, success has been frequently limited, in particular when treating late-stage solid tumors. There still is the need to develop smart and synergistic therapeutic approaches to achieve the synthesis of strong and effective drugs and delivery systems. Much interest has been paid to the development of smart drug delivery systems (drug-loaded particles) that utilize passive targeting, active targeting, and/or stimulus responsiveness strategies. This review will summarize some main ideas about the effect of each strategy and how the combination of some or all of them has shown to be effective. After a brief introduction of current cancer therapies and their limitations, we describe the biological barriers that nanoparticles need to overcome, followed by presenting different types of drug delivery systems to improve drug accumulation in tumors. Then, we describe cancer cell membrane targets that increase cellular drug uptake through active targeting mechanisms. Stimulus-responsive targeting is also discussed by looking at the intra- and extracellular conditions for specific drug release. We include a significant amount of information summarized in tables and figures on nanoparticle-based therapeutics, PEGylated drugs, different ligands for the design of active-targeted systems, and targeting of different organs. We also discuss some still prevailing fundamental limitations of these approaches, eg, by occlusion of targeting ligands.Keywords: active targeting, drug delivery systems, EPR effect, nanoparticles, passive targeting, stimulus-responsive targeting
