Hybrid nanocomposite curcumin-capped gold nanoparticle-reduced graphene oxide: Antioxidant potency and selective cancer cytotoxicity

Source: Hybrid nanocomposite curcumin-capped gold nanoparticle-reduced graphene oxide: Antioxidant potency and selective cancer cytotoxicity

Among the various nanomaterials reported to date, graphene has ascended as the ‘wonder material’ and ‘shining star’, with a Nobel Prize awarded in 2010 for its discovery [1]. Due to the interesting chemical, mechanical, and optical properties, graphene applications have been actively pursued in the general biomedical fields, with distinctive focus on cancer nanomedicine, to confront the increasing cancer mortality rates [2–7]. In this context, graphene offers a range of nano-therapeutic modalities of phototherapy, drug delivery, and combination therapy [8–10]. This enables efficient support for functionalization and drug loading [11, 12], in addition to enhanced mechanical stability and cellular interactions [13]. The few limitations of graphene such as hydrophobicity and self-aggregation, can be effectively resolved via suitable functionalization and composite hybrid fabrication [14]. In fact, various studies have proven advantageous attributes using graphene-based composites (GBCs) in cancer nano-therapy, over raw un-functionalized graphene counterparts [15–17]. Nevertheless, the progress and development of these composites to the next in vivo and clinical stages remains slow [12]. The main barrier recognized is the safety profile, or biocompatibility and selectivity, of these composites towards normal tissue [12, 13]. After all, drug selectivity and enhanced patients’ life quality are the ultimate goal of nanotechnology in cancer treatment [18, 19].

For successful and selective cancer nano-therapy applications, more attention needs to be directed to GBCs fabrication and pre-clinical trials, as these processes constitute the basic foundation for further development and progress. In fact, careful design and suitable choice of raw materials and synthesis methodology are suggested approaches to increase GBCs biocompatibility [13, 20]. Accurate reporting of the selectivity index (SI) in pre-clinical in vitro testing is also an important factor determining safety and indicating successful employment of raw materials in cancer-active, normal cell-biocompatible composites. As such, current nanomedicine research indicates that graphene selection as a starting build-up template secures essential planar surface area that is suitable for functionalization and drug upload [21]. On the other hand, gold nanoparticles (AuNPs) stand out as a prominent functional moiety used heavily with various nanomaterials [11, 22], due to the stable [23], well-established biocompatible features that enhance the overall composite selectivity [11, 24]. Consequently, graphene-AuNPs hybrid composite is one of the best-studied materials in the field of cancer nano-therapy [25–29]. Furthermore, there is a mounting focus devoted to the hybridization and synthesis methodology used to combine different moieties into one nanocomposite. Green synthesis is recently identified as an easy, eco-friendly, cost-effective, safe, and efficient alternative to conventional chemical synthesis, further reinforcing biological activities of the whole system [30, 31]. As a result, there are various reports of GBCs synthesized by green methods (S1 Table), yet the majority show inconsistent use of human cancer/normal cell lines, with a lack of SI reporting in respective target tissues, which may contribute to indeterminate conclusions and hinder further development [13].

Apart from synthesis approaches, the suitable anti-cancer drug incorporation holds fundamental values and merits. Plant-derived drugs account for over 60% of drugs introduced worldwide recently [32], including Curcuma longa polyphenolic extract curcumin (CR), which has been the focal point of modern cancer research [33, 34]. Its major advantage lies in its multi-targeted therapeutic approach, which is of utmost importance to confer cancer disease that holds more than 500 gene products dysregulation [34, 35]. The astonishing ability of CR to inhibit tumor proliferation, cell cycle, metastasis, and angiogenesis is limited by its low bioavailability [34, 35]. Therefore, CR nano-formulations are prescribed as a valid solution [36]. In this study, we suggest, for the first time, the one-pot combination of all these beneficial attributes of graphene, AuNPs, and CR into one novel green nanocomposite, namely CR-capped AuNPs-reduced graphene oxide (CAG). Unlike previous reports of CR combining with GBCs through two-step chemical reactions [37, 38], this work proposes a novel green, simple, onepot synthesis which uses CR to its fullest potential as a natural reducing agent, with capping and functionalization moiety during synthesis, while also preserving its anti-oxidant, cancer cytotoxic, and selective biological activities. This structure is anticipated to confer superior features, overcoming the limitations faced by each single component, in addition to being a green and safe product with no toxic impurities and increased biocompatibility. Comprehensive in vitro cancer cytotoxicity and respective selectivity indices are discussed in the current work, in terms of various concentrations, time points, and cell lines chosen to represent suitable target colon cancer tissue and distant normal liver cells, which mimic the probable in vivo behavior of GBCs as reported previously [39, 40]. We believe, as recommended by nano-toxicology reviews [41], that careful design and accurate SI measurement will improve knowledge gathered at the preliminary in vitro stage, creating a worthwhile template eligible for various biomedical applications and further study and development.

References can be found in the full paper.

READ FULL PAPER HERE...