Since the classic talk from Richard Feynman, titled 'There's plenty of room at the bottom’ , presented on 29 December 1959 at the annual meeting of the American Physical Society (at the California Institute of Technology, USA), introduced the concept of nanotechnology, this technology has evolved at an outstanding pace in practically all areas of sciences [1, 2]. To be considered as nanotechnology, nanosized and nanostructured systems should present one or more components with at least one dimension ranging from 1 to 100 nm. In recent years, innovation in nanotechnology and nanoscience for medicine (or nanomedicine) has been a major driving force in the creation of new nanocomposites and nanobioconjugates. Essentially, these materials may bring together the intrinsic functionalities of inorganic nanoparticles and the biointerfaces offered by biomolecules and polymers of natural origin, such as carbohydrates and derivatives, glycoconjugates, proteins, DNA, enzymes and oligopeptides [3–5].
In view of the large number of available alternatives to produce hybrids and conjugates for bioapplications, carbohydrates have been often chosen, due to their biocompatibility, physicochemical and mechanical properties, and relative chemical solubility and stability in aqueous physiological environment [5–8]. Among these carbohydrates, chitosan (poly-β(1 → 4)-2-amino-2-deoxy-d-glucose) is one of the most abundant polysaccharides (semi-processed) from natural sources, second only to cellulose [5–8]. Chitosan is a polycationic polymer that has been broadly used in pharmaceuticals, drug carrier and delivery systems, wound dressing biomaterial, antimicrobial films, biomaterials, food packaging and many applications [5–10]. Chitosan is mainly produced from the alkaline deacetylation of chitin (usually extracted from the shells of marine crustaceans, such as crabs and shrimps), forming a copolymer composed of N-acetyl-d-glucosamine and d-glucosamine units available in different grades, depending upon the content of the acetylated moieties [5–8]. The degree of deacetylation (DD) and the molar mass (MM) of chitosan influence its properties, such as solubility in water, mechanical behaviour, chemical stability and biodegradability. Similarly, there are several alternatives of one-dimensional and zero-dimensional nanostructured inorganic materials, such as nanotubes, nanowires, nanorods and quantum dots, that are suitable for conjugation with carbohydrates to produce hybrid nanomaterials for bioapplications [11–13]. Quantum dots (QDs) are ultra-small semiconductor nanocrystals that consist of numbers of atoms in the range of a few thousands. Owing to their reduced dimension, QDs exhibit discrete electronic energy levels that give rise to unique electronic, optical and magnetic properties [13–16]. They have rapidly emerged as a new class of fluorescent nanomaterials for a boundless number of applications, primarily as probes in biology, medicine and pharmacy. Having many advantages over organic dyes, such as broad excitation and resistance to photobleaching, QDs are one of the most exciting tools for use in nanotechnology, nanomedicine and nanobiotechnology areas . However, to be used in biological conditions, QDs must exhibit compatibility to the water-based physiological medium in which the large number of natural macromolecules exist. Therefore, surface chemical engineering of QDs is required to render them water soluble and biocompatible. Surprisingly, reports on the surface bio-functionalisation of QDs with chitosan and its derivatives are scarcely found in the literature [5, 17–20], and only recently has the direct synthesis of CdS QDs using chitosan and chemically modified chitosans in aqueous colloidal dispersion been published by our group [17–19]. Despite the noticeable advances in the synthesis of nanohybrids based on the conjugation of QDs and biomolecules, to date, most published studies and commercial QDs are synthesised through the traditional organometallic method and contain toxic elements, such as cadmium, lead and mercury, using organic solvents and ligands (trioctyl phosphine/trioctyl phosphine oxide, TOP/TOPO) at high temperatures. Presently, the most commonly used QDs contain divalent cadmium, widely known as a toxin, due to the accumulation of Cd2+ in tissues and organs [13, 21, 22]. Although Cd2+ is incorporated into a nanocrystalline core (as components of low-solubility sulphides or selenides) covered by another semiconductor 'shell’ like ZnS and surrounded by biologically compatible ligands, such as polymers, amino acids, proteins and carbohydrates [23–27], it is still unclear if these toxic ions will impact the use of QDs as clinical luminescent probes for biomedical applications. Consequently, great concern has been raised over the toxicity of QDs made by heavy-metal cores in living cells, animals and humans, and in the environment as the long-term impact is not entirely understood [5, 22]. In that sense, 'cadmium-free’ nanomaterials are very promising alternatives, such as zinc compounds [5, 28], due to their natural environmental abundance. Zinc divalent cations (Zn2+) are commonly found in nature, in forms varying from mineral inorganic sources to several living organisms as crucial metabolic species.
Thus, this research focused on demonstrating the synthesis of ZnS quantum dots directly capped by chitosan using a facile, reproducible and economical single-step aqueous processing method at room temperature. Moreover, the nanohybrid systems were extensively characterised, and the strong influence of pH on the formation of the semiconductor nanocrystals and their fluorescent response was verified. The novel colloidal biofunctionalised water-soluble nanoconjugates made of ZnS-QDs/chitosan are potentially non-toxic and, combined with their luminescent properties, offer great potential for use in various biomedical and environmentally friendly applications.