Synthesis and Characterization of Nanodiamond-Doxorubicin (Dox) Conjugate for Effective Delivery against MCF-7 Cell Lines

Abstract

In this work, we have introduced a carbon nanomaterial (nanodiamond), to bind with anticancer drug doxorubicin (DOX) with via amide bond conjugation for cancer drug delivery and therapy. Nanodiamond (ND) was initially carboxylated by the surface modification along the treatment with strong alkaline solution (H2SO4:HNO3) and then activated the carboxyl moiety of ND with the addition of EDC. Anticancer drugs were bound to the ND through a succession of chemical modifications by adipic acid dihydrazide (ADH). The ND-Drug conjugate was analyzed by Nuclear Magnetic Resonance (1H-NMR) Spectroscopy, Fourier Transform Infrared (FTIR) Spectroscopy and Mass Spectroscopy (MS), Atomic Force Microscopy (AFM), Particle size, Zeta potential, Drug release, SRB assay against MCF-7 cells, and DNA fragmentation. Spectroscopic analysis confirms the conjugation of nanodiamond with different anticancer drug. AFM photomicrograph represents the surface morphological features of ND-DOX conjugates. In- vitro investigation showed that ND-DOX conjugates have slow and sustained drug release characteristics. In-vitro cytotoxicity studies, an enormous cytotoxic potential of ND-Drug conjugates were showed against cancer cell line. Above all findings were suggested that the ND-DOX conjugates may be a potential inhibitor of MCF-7 cancer cells to act as a drug candidate. According to all these data it can be confirm that the ND-DOX conjugates could be an effective agent for drug delivery and could be promising in future for tumor targeting strategy.
 Keywords: Nanodiamond, Sustained Release, Drug Delivery, Cytotoxicity, Conjugates

Combined Nanochemotherapy Using Doxorubicin and Curcumin as an Example

“…Therefore, the development of alternative polymers to replace PEG is needed [40]. In other cases, it is necessary to have polymers that capture, solubilize and control the release of the drug without resorting to chemical conjugation [36], such as Pluronic® micelles [34,41,42], poly(lactic acid) (PLG ), poly(lactic co-glycolic acid) (PLGA) [43], chitin [44,45], chitosan [34,35,42]. For example, a multifunctional co-delivery system that coencapsulates hydrophobic chemotherapeutic drugs (curcumin) and hydrophilic therapeutic drugs (Survivin shRNA genes) in polymer nanoparticles (PLGA polymer and conjugated triblock polymer) is a promising strategy for clinical application in cancer therapy [46].…”

“…Biodegradable polymers with a high molecular weight include: polypeptides, dextrins, polysialic acid, polyacetals [36], PLG, PLGA [43], chitosan [34,35], PEG micelles [47], alginate [48], albumin [49][50][51][52][53], pluronic micelles (Pluronic®) [34,41,42,49]. Recently, polyglutamic acid (PGA), which has a high potential among synthetic polypeptides, has been used in nanomedicine [36].…”

“…The process of self-assembly is an interesting tool [36]. In recent decades, Pluronic® [49,60] has been developed to prepare micelles that can be modified [34,41,42]. It is known that micelles formed by pluronic triblock copolymers are a promising class of drug delivery agents [49].…”

“…Their molecules degrade in the biological environment [61], and due to the hydrophobicity of the core and steric factors, they have the ability to encapsulate hydrophobic agents [49,42]. Pluronics L61, P85, P105, PF127 [34,49,62,63], or P85 [42] and F68 [41,49,62] are most often used in micelles.…”

“…NPs made using nanodiamonds (ND) are useful components for research in nanomedicine due to their relatively small size and chemical inertness. They have the possibility of flexible surface modification, which in general makes them positive elements for various biological applications [41,64,65]. In vitro studies have shown that ND-Dox + Pluronic® F 68 conjugates have slow and sustained drug release characteristics and tremendous cytotoxic potential against the MCF-7 breast cancer cell line.…”