Curcumin and isonicotinic acid hydrazide functionalized gold nanoparticles for selective anticancer action

https://doi.org/10.1016/j.colsurfa.2020.125484Get rights and content

Highlights

  • A new approach to improve potential of gold nanoparticles is demonstrated by developing a suitable surface corona.

  • The curcumin and isonicotinic acid hydrazide formed a functional corona on gold nanoparticles for anticancer action.

  • Investigations on human lung squamous carcinoma and human lung fibroblasts indicate selective toxicity.

  • The work reveals that facile surfaces on nanoparticles are important in controlling bio-medical potential of nanoparticles.

Abstract

Besides physicochemical properties, careful design of biomolecular surface corona can dictate therapeutic potential of nanoparticles. Therefore, we demonstrate a new approach to improve the anticancer potential of gold nanoparticles (AuNPs) by developing a strong corona of curcumin and isonicotinic acid hydrazide (INH) around them. Here, curcumin reduced AuNPsCur are surface-functionalized with biologically active INH (AuNPsCur@INH). Our investigations on human lung squamous carcinoma (LK-2) and human lung fibroblast (TIG-120) cells indicate selective toxicity of functionalized nanoparticles. Conjugation of curcumin and INH on the surface of AuNPs induced anticancer action through reactive oxygen species (ROS) generation. The further extension of this study revealed apoptosis and morphological changes in LK-2 and TIG-120 cells, respectively. Moreover, the anticancer potential of these nanoparticles is compared with standard cisplatin. The outcomes of the work determine that the facile functional surfaces on nanoparticles can be important in controlling the biological activities of nanoparticles.

Graphical abstract

A surface corona of curcumin and isonicotinic acid hydrazide is developed on gold nanoparticles for improved anticancer activity. The selective toxicity of functional nanoparticles is shown on human lung squamous carcinoma, and cytocompatibility towards human lung fibroblasts.

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Introduction

Multimodal gold nanoparticles (AuNPs) are one of the most emerging nanomaterials, and they are extensively being used in genomics, cancer treatments, pharmacological cargo delivery, DNA immunization, biosensing, and microorganism’s management [[1], [2], [3], [4], [5]]. Further, due to ease in fine-tuning of shape, size and surface chemistry, AuNPs find immense applications in immunogenic carriers and adjuvants, photodynamic, and -thermal therapies [6,7]. The inert nature of AuNPs coupled with their inherent nanozyme potential leads to surface-enhanced Raman scattering (SERS), and makes them an attractive material for nanozyme-based detection systems [8]. Moreover, AuNPs are a popular choice of materials due to their non-toxicity, biocompatibility and non-immunogenicity; which are akin to several biodegradable nanomaterials like liposomes, dendrimers, chitosan, gelatin, polymethyl methacrylate, and poly(lactide-co-glycolic acid) [4,9]. Furthermore, by fine-tuning the important physicochemical properties of AuNPs including their size, shape, composition, surface charge, and surface chemistry, it is possible to manipulate characteristic nature of AuNPs according to their potential application [10].

In the context of above, our group has designed isoniazid or isonicotinic acid hydrazide (INH) surface-coated AuNPs, and investigated their nanozyme activity, highly efficient and selective antimicrobial potential and anti-mycobacterium ability [5]. The INH is a first-line medication used in tuberculosis (TB), and conventionally it is used as a combinatorial medicine. However, long term usages of INH based treatments are often discontinued due to its toxicity. Nevertheless, it has been reported that the amelioration of INH toxicity can be accomplished by co-administrating of polyphenols such as amino-phenols, curcumin (Cur), or vitamin B [11]. Motivated from the belief, in the present work, we have synthesized AuNPs with curcumin (AuNPsCur), and successively surface coated with INH moieties (AuNPsCur@INH), anticipating that the presence of curcumin can combat the toxicity caused by the INH. In this perspective, it is also important to state that the tuberculosis is known to induce idiosyncratic toxicity; one such toxicity can be attributed to the induction of lung adenocarcinoma, which is known to be effortlessly metastasized. Several reported cases indicate that tuberculosis can increase the risk of lung cancer owing to inflammation, fibrosis, and subsequent immunosuppression. Contrarily, many of the reports reveal the induction of tuberculosis in patients with a history of lung cancer [12], and cancer has been pharmaceutically targeted via cancer immunology, microenvironment, genetics, metabolism and oxidative stress [[13], [14], [15]]. In the milieu of oxidative stress, reactive oxygen species (ROS) are generated due to the respiratory metabolism in the electron transport chain (ETC), and behave like a double-edge sword that contributes to cancer by activating oncogenic genes, hypoxic conditions and elevated integrin levels [13]. In this direction, many analogues of curcumin have demonstrated improved anti-cancerous efficiency but limited by reduced solubility.

Curcumin [diferuloylmethane or 1,7-bis(4-hydroxy-3-methoxy phenyl)-2,6-heptadine-3.5-dione] is the principle curcuminoid of a rhizomatous herbaceous perennial plant of Curcuma longa, a member of the ginger family Zingiberaceae. Curcumin is best known for its anti-cancerous, antioxidant, anti-inflammatory, antibiotic and anti-mutagenic properties which is aggressively investigated for treatment in Alzheimer’s disease, ageing [16], cancer [17], depression [18], diabetes, myocardial infarction [19], rheumatoid arthritis [20] and in upregulating wound healing mechanism [21,22]. Amassing huge beneficial effects, curcumin fails to deliver adequate bioavailability because of its lower absorption, rapid metabolism and elimination [23]. Many adjuvants such as piperidine, liposomes, phospholipid complexes, and metallic nanoparticles are known to improve its bioavailability [[24], [25], [26]]. In this context, a curcumin-loaded PLGA [Poly(d, l-lactide-co-glycolic acid)] micromagnetic composite system has been developed, and it was found to have cytotoxicity against HeLa cell lines with a significant potency [27]. Therefore, we believe that presentation of curcumin on AuNPs will not only control the noxiousness of INH but also improve the potential utility of curcumin for bio-medical applications.

Therefore, we have developed sequence surface functionalized AuNPs with curcumin and INH as shown in Fig. 1A and assessed their anti-cancerous activity on human lung squamous LK-2 carcinoma cells, whereas the cytotoxicity of these nanoparticles is investigated towards human lung TIG-120 fibroblast cells.

Section snippets

Materials and chemicals

Curcumin, fetal bovine serum (FBS), isoniazid or isonicotinic acid hydrazide (INH), potassium hydroxide (KOH), tetrachloroauric acid (HAuCl4) were procured from Sigma Aldrich (St. Louis, Missouri, United States); the phosphate-buffered solution (PBS) tablets were purchased from Takara (Shiga, Japan); Hank’s balanced salt solution (HBSS), Alpha minimum essential medium (α-MEM) and Dulbecco`s modified eagle media (DMEM) were obtained from Gibco (Carlsbad, CA, United States); the antibacterial

Results and discussion

Previously, AuNPs have been synthesized with curcumin, which works as a green reducing agent, and surface availability of curcumin on nanoparticles exert potential biological applications [[29], [30], [31], [32], [33], [34]]. It has been established that the AuNPs are prepared by the reduction of AuCl4, and both phenolic-OH and enolic-OH of curcumin help in the reduction of metal ions to form AuNPs, as illustrated in Fig. 1C. In the present work, we have synthesized AuNPsCur and further

Conclusions

In this study, we demonstrate the important role of nanoparticle’s surface corona towards selective biological action, which has often been overlooked. Here, we have employed a sequential surface-functionalization approach to acquire a stable surface corona of curcumin and INH on AuNPs. This study shows that AuNPs act as an excellent carrier and stabiliser for curcumin and INH molecules. Investigations on human lung cancer and human fibroblast confirmed the selective toxicity of nanoparticles

CRediT authorship contribution statement

Akhela Umapathi: Methodology, Writing - original draft, Formal analysis, Conceptualization, Data curation, Investigation. Navya PN: Methodology, Formal analysis, Writing - review & editing. Harishkumar Madhyastha: Investigation, Validation, Writing - review & editing. Mandeep Singh: Investigation, Writing - review & editing, Methodology. Radha Madhyastha: Investigation, Methodology, Validation. Masugi Maruyama: Supervision, Writing - review & editing, Resources. Hemant Kumar Daima:

Declaration of Competing Interest

The authors report no declarations of interest.

Acknowledgments

AU acknowledges the VRC scholarship provided by Rao Bahaddur Dharmapravartha Gubbi Thotadappa Charities, Bengaluru, India. The generous support of Japan Science and Technology (JST) Agency, Japantoward Asia Youth Exchange Program in Science (Sakura Exchange Program) is duly accredited by AU, NPN and HKD. Further, HKD appreciates the Centre for Advanced Materials and Industrial Chemistry (CAMIC) in the School of Sciences, RMIT University, Australiafor an Honorary Visiting Research Fellowship.

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