title: Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review.
abstract: As the mainstay in the treatment of various cancers, chemotherapy plays a vital role, but still faces many challenges, such as poor tumour selectivity and multidrug resistance (MDR). Targeted drug delivery using nanotechnology has provided a new strategy for addressing the limitations of the conventional chemotherapy. In the last decade, the volume of research published in this area has increased tremendously, especially with functional nano drug delivery systems (nanocarriers). Coupling a specific stimuli-triggered drug release mechanism with these delivery systems is one of the most prevalent approaches for improving therapeutic outcomes. Among the various stimuli, pH triggered delivery is regarded as the most general strategy, targeting the acidic extracellular microenvironment and intracellular organelles of solid tumours. In this review, we discuss recent advances in the development of pH-sensitive nanocarriers for tumour-targeted drug delivery. The review focuses on the chemical design of pH-sensitive biomaterials, which are used to fabricate nanocarriers for extracellular and/or intracellular tumour site-specific drug release. The pH-responsive biomaterials bring forth conformational changes in these nanocarriers through various mechanisms such as protonation, charge reversal or cleavage of a chemical bond, facilitating tumour specific cell uptake or drug release. A greater understanding of these mechanisms will help to design more efficient drug delivery systems to address the challenges encountered in conventional chemotherapy.
authors.affiliation: School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1142, New Zealand.
authors.forename: Manju
authors.initials: M
authors.lastname: Kanamala
authors.affiliation: Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1142, New Zealand.
authors.forename: William R
authors.initials: WR
authors.lastname: Wilson
authors.affiliation: School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1142, New Zealand.
authors.forename: Mimi
authors.initials: M
authors.lastname: Yang
authors.affiliation: Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1142, New Zealand.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Palmer
authors.affiliation: School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1142, New Zealand. Electronic address: z.wu@auckland.ac.nz.
authors.forename: Zimei
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D049329:Nanostructures / Q000737:chemistry; D036103:Nanotechnology; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D001672:Biocompatible Materials
keywords: Intracellular delivery; PEG detachment; Protonation; Tumour targeted drug delivery; pH-sensitive bond; pH-sensitive nanocarriers