One pot synthesis of carbon dots decorated carboxymethyl cellulose- hydroxyapatite nanocomposite for drug delivery, tissue engineering and Fe3+ ion sensing
Introduction
Cellulose is the most abundant renewable polymer available in nature. Materials based on cellulose and its derivatives particularly carboxymethyl cellulose (CMC) have been widely used in a variety of applications for their fascinating properties such as hydrophilicity, biodegradability, biocompatibility and ease of processibility (Chang & Zhang, 2011). Due to these properties, it has been extensively studied in biomedical field, ranging from tissue engineering to drug delivery (Camponeschi et al., 2015, Guo et al., 2015, Kono, 2014). Compared to pure form, cellulose-inorganic hybrid materials have attracted increasing attention for their superior properties such as less swelling degree, higher mechanical properties and exceptional bioactivity (He, Chang, Peng, & Zhang, 2012). So far, hydroxyapatite (HA) is the most appropriate inorganic material for this purpose due to its close similarity with inorganic component of natural bone; induces excellent bioactivity in the composites. Recently, researchers have introduced hydroxyapatite into carboxymethyl cellulose in an effective way to combine the advantages of cellulose and hydroxyapatite; and develop materials with high functionality (Fragal et al., 2016). Consequently, carboxymethyl cellulose-hydroxyapatite (CMC-HA) composite has emerged as one of the most promising material in biomedical field (Pasqui, Torricelli, Cagna, Fini, & Barbucci, 2014; Azzaouia et al., 2017).
Currently, researchers have designed HA based nanocomposite and applied in multiple applications. For example, Azzaouia and co-authors synthesized a tri-functional CMC-HA composite and employed as (i) toxic material absorbent; (ii) antimicrobial and antifungal composite; and (iii) a candidate for bone tissue engineering (Azzaouia et al., 2017). In the present work, we have aimed to synthesize a CMC-HA composite for diverse applications such as in tissue engineering, drug delivery and metal ion sensing. To develop a smart drug carrier as well an intelligent ion sensor, it is essential to conjugate fluorescent molecules or particles with the composite.
Carbon dots (CDs), a luminescent nanomaterial has been extensively studied due to its low cost, facile synthesis, hydrophilicity, high photostability and excellent biocompatibility. In recent years, there is a growing interest in developing surface functionalized nanomaterials with CDs for drug delivery; so that it can be accurately traced in cells and tissues. In our previous work, we have demonstrated the CDs embedded nanoscale metal organic frameworks for potential drug delivery (Chowdhuri, Singh, Ghosh, & Sahu, 2016). Furthermore, CDs have excellent ability to detect various metal ions by taking the advantages of its surface functional groups. The fluorescent quenching behavior of CDs after combination with metal ions; is the main aspect to use CDs as a sensing probe (Lv et al., 2017). These properties motivate us to expand the application scopes of CMC-HA composite from bone tissue engineering to drug delivery and metal ion sensing; with the incorporation of CDs. In the past few years, groups of researchers worked separately to fabricate CDs conjugated HA and CDs conjugated cellulose for different applications. Zhao and co-authors synthesized CDs conjugated F-substituted hydroxyapatite for cellular imaging (Zhao, Shi, Fang, & Feng, 2015). Guo et al. reported biomimetic calcium phosphate/CDs composites for cell labeling and copper ions detection (Guo et al., 2016). Gogai and co-authors developed CDs decorated HA nanohybrid for bone tissue engineering (Gogai, Kumar, Mandal, & Karak, 2016). You et al. designed a transparent sunlight conversion film by the conjugation of CDs with CMC (You, Zhang, Liu, & Lei, 2016). Lv et al. synthesized a CDs-bacterial cellulose composite for Fe3+ ion detection (Lv et al., 2017). In most of the reported literatures, conjugation of CDs was a complex lengthy process. Recently, two groups of researchers showed the possibilities of direct carbonization of cellulose to high fluorescent CDs by a simple hydrothermal process (Wu, Li, Tan, Wu, & Liu, 2015; Li et al., 2017). It inspired us to synthesize CDs conjugated CMC-HA nanocomposite directly from CMC-HA nanocomposite through a simple thermal route. In this study, we have developed a one pot method to synthesize carbon dots decorated CMC-HA nanocomposite for applications in bone tissue engineering, drug delivery and metal ion sensing arena. Initially, we have synthesized CMC-HA nanocomposite through in-situ mineralization process and refluxed it at 140 °C for 8 h to get fluorescent enabling CDs conjugated CMC-HA nanocomposite; and subsequently applied for multiple biomedical applications.
It is well known that the excessive amount of Fe3+ ions in human body cause serious diseases like Parkinson’s disease, Alzheimer’s disease, liver, and kidney damage. In view of this issue, the selective and sensitive detection of Fe3+ ions are very important (Wang et al., 2016). The synthesized CDs-CMC-HA nanocomposite showed excellent selectivity towards Fe3+ ions over other metal ions. In this study, we have introduced a novel CDs conjugated CMC-HA nanocomposite (CDs-CMC-HA) possess the following notable advantages − (1) synthesized through a cost effective one-pot method; (2) having excellent properties for drug loading, release and imaging; (3) bone regenerative property; and (4) good sensitivity for Fe3+ ions.
Section snippets
Materials and chemicals used
Sodium salt of carboxymethyl cellulose (degree of substitution 0.9), calcium nitrate tetra hydrate ( > 98% assay), di-ammonium hydrogen phosphate and liquid ammonia ( > 25% assay) were purchased from Merck, Mumbai, India. Anticancer drug doxorubicin and dialysis membrane (MWCO 3.5 KD) were purchased from Sigma Aldrich. Fetal bovine serum (FBS), phosphate buffer solution (PBS), Dulbecco’s modified eagle’s medium (DMEM) were purchased from Himedia, India, and Hyclone, USA respectively. Millipore
Results and discussion
In this study, carboxymethyl cellulose has been established as an active functional material due to its recognizable contribution in in-situ mineralization of HA and the formation of high fluorescent CDs through carbonization. The schematic presentation of the starting CMC-HA formation step followed by CDs-CMC-HA formation to drug loading and release behavior of CDs-CMC-HA are shown in Fig. 1.
Conclusion
The present work demonstrated the successful fabrication of fluorescent enabling carbon dots conjugated CMC-HA nanocomposite through a simple one pot method. The synthesized CDs-CMC-HA nanocomposite exhibited an intense blue emission at 440 nm with high stability. In this report, the functionality of synthesized CDs-CMC-HA nanocomposite has been explored in three directions particularly in bone tissue engineering, drug delivery and ion sensing arena. Synthesized nanocomposite showed cell
Conflict of interest
The authors declare no conflict of interest
Acknowledgements
The authors would like to acknowledge In house project support group (iPSG) (OLP-0231), CSIR- National Metallurgical Laboratory for financial support and research facilities. The authors also like to acknowledge the Indian Institute of Technology (Indian School of Mines) [IIT-ISM], Dhanbad for providing characterization facilities. Author (Chandrani Sarkar) acknowledges University Grants Commission, India for granting Fellowship.
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