Chitosan Nanoparticles for Targeted Cancer Therapy: A Review of Stimuli-Responsive, Passive, and Active Targeting Strategies

Abstract

Jafar RMH Al-Shadidi,1 Shahad Al-Shammari,1 Danah Al-Mutairi,1 Dalal Alkhudhair,1 Hnin Ei Thu,2 Zahid Hussain1,3 1Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates; 2Department of Pharmacology, Faculty of Dentistry, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor Branch, Selangor, Malaysia; 3Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab EmiratesCorrespondence: Zahid Hussain, Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates, Email [email protected]: Despite all major advancements in drug discovery and development in the pharmaceutical industry, cancer is still one of the most arduous challenges for the scientific community. The implications of nanotechnology have certainly resolved major issues related to conventional anticancer modalities; however, the undesired recognition of nanoparticles (NPs) by the mononuclear phagocyte system (MPS), their poor stability in biological fluids, premature release of payload, and low biocompatibility have restricted their clinical translation. In recent decades, chitosan (CS)-based nanodelivery systems (eg, polymeric NPs, micelles, liposomes, dendrimers, conjugates, solid lipid nanoparticles, etc.) have attained promising recognition from researchers for improving the pharmacokinetics and pharmacodynamics of chemotherapeutics. However, the specialty of this review is to mainly focus on and critically discuss the targeting potential of various CS-based NPs for treatment of different types of cancer. Based on their delivery mechanisms, we classified CS-based NPs into stimuli-responsive, passive, or active targeting nanosystems. Moreover, various functionalization strategies (eg, grafting with polyethylene glycol (PEG), hydrophobic substitution, tethering of stimuli-responsive linkers, and conjugation of targeting ligands) adapted to the architecture of CS-NPs for target-specific delivery of chemotherapeutics have also been considered. Nevertheless, CS-NPs based therapeutics hold great promise for improving therapeutic outcomes while mitigating the off-target effects of chemotherapeutics, a long-term safety profile and clinical testing in humans are warranted for their successful clinical translation.Keywords: chitosan nanoparticles, targeted cancer therapy, tumor microenvironment, stimuli-responsive targeting, passive targeting, active targeting

Keywords

• chitosan nanoparticles
• targeted cancer therapy
• tumor microenvironment
• stimuli-responsive targeting
• passive targeting
• active targeting