Surface Modification of Titanate Nanotubes with a Carboxylic Arm for Further Functionalization Intended to Pharmaceutical Applications

Abstract

Nanotechnology is playing a significant role in modern life with tremendous potential and promising results in almost every domain, especially the pharmaceutical one. The impressive performance of nanomaterials is shaping the future of science and revolutionizing the traditional concepts of industry and research. Titanate nanotubes (TNTs) are one of these novel entities that became an appropriate choice to apply in several platforms due to their remarkable properties such as preparation simplicity, high stability, good biocompatibility, affordability and low toxicity. Surface modification of these nanotubes is also promoting their superior characters and contributing more to the enhancement of their performance. In this research work, an attempt was made to functionalize the surface of titanate nanotubes with carboxylic groups to increase their surface reactivity and widen the possibility of bonding different molecules that could not be bonded directly. Three carboxylic acids were investigated (trichloroacetic acid, citric acid and acrylic acid), and the prepared composites were examined using FT-IR and Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The toxicity of these functionalized TNTs was also investigated using adherent cancer cell lines and fibroblasts to determine their safety profile and to draw the basic lines for their intended future application. Based on the experimental results, acrylic acid could be the suitable choice for permanent surface modification with multiple carboxylic groups due to its possibility to be polymerized, thus presenting the opportunity to link additional molecules of interest such as polyethylene glycol (PEG) and/or other molecules at the same time.

An Overview of Hydrothermally Synthesized Titanate Nanotubes: The Factors Affecting Preparation and Their Promising Pharmaceutical Applications

“…As TNTs have promising potential to be used in multiple applications, their fragile structure should be taken into consideration, as it could undergo numerous changes during handling/processing. For example, TNTs could be easily broken up due to mechanical forces such as stirring or ultrasonication, resulting in shorter nanotubes [10,37]. Also, extremely high-temperature treatments used in many procedures could result in changing the surface chemistry and reducing the number of OH groups on it.…”

“…Furthermore, their safety/toxicity studies still present conflicting results. Some studies have reported their safe use without showing any toxic effects [7,10,80]. Others even displayed positive outcomes such as increased cell viability [8], enhanced proliferation, and bone cell adhesion [81], probably due to their porous structure allowing the flow of nutrients and blood [82], while other studies reported their toxic effects and classified them as more toxic than other nanomaterials such as nanorods, nanoribbons, and nanowires [83,84].…”

“…Others even displayed positive outcomes such as increased cell viability [8], enhanced proliferation, and bone cell adhesion [81], probably due to their porous structure allowing the flow of nutrients and blood [82], while other studies reported their toxic effects and classified them as more toxic than other nanomaterials such as nanorods, nanoribbons, and nanowires [83,84]. However, the potential utilization of TNTs in health-related applications is supported by the promising results obtained by numerous studies which investigated their cytotoxicity using different cell lines (intact and cancerous) with different concentrations (range from 1 µg/mL to 5 mg/mL) and different times of exposure (from short treatment of 120 min to long exposure of 7 days) [7,8,10,85]. Even surface-modified TNTs with several molecules (silane, stearate, polyethyleneimine, acrylic acid-polyethylene glycol copolymer) have presented similar results which could promote the shifting of TNTs (bare and surface-modified) to the health domain [9,10,61].…”

“…However, the potential utilization of TNTs in health-related applications is supported by the promising results obtained by numerous studies which investigated their cytotoxicity using different cell lines (intact and cancerous) with different concentrations (range from 1 µg/mL to 5 mg/mL) and different times of exposure (from short treatment of 120 min to long exposure of 7 days) [7,8,10,85]. Even surface-modified TNTs with several molecules (silane, stearate, polyethyleneimine, acrylic acid-polyethylene glycol copolymer) have presented similar results which could promote the shifting of TNTs (bare and surface-modified) to the health domain [9,10,61].…”

“…Pharmaceutics 2024, 16, x FOR PEER REVIEW 2 of 19 nano-size combined with tubular structure are unique properties which differentiate them from other types of nanoparticles (NPs), giving them higher surface area and cellular uptake [3,4]. Moreover, TNTs offer a distinguished profile of specifications that could be interesting in numerous fields, such as their hydrophilic nature, good wettability and biocompatibility [2,3,5], chemical stability [5], photocatalytic activity [5], excellent mechanical properties, and corrosion resistance [5,6], in addition to low toxicity [7][8][9][10]. Due to these remarkable specifications, TNTs have been successfully utilized in numerous fields with great outcomes and impressive performance (Figure 1) making them attractive candidates for investigation of their potentials in further disciplines [5,[11][12][13].…”