Targeted Delivery of Docetaxel by Use of Transferrin/Poly(allylamine hydrochloride)-functionalized Graphene Oxide Nanocarrier

Abstract

The exceptional chemical and physical properties of graphene oxide (GO) make it an attractive nanomaterial for biomedical applications, particularly in drug delivery. In this work we synthesized a novel, GO-based nanocarrier for the delivery of docetaxel (DTX), a potent hydrophobic chemotherapy drug. The GO was functionalized with transferrin (Tf)-poly(allylamine hydrochloride) (PAH), which provided targeted and specific accumulation to extracellular Tf receptors and stabilized GO in physiological solutions. Tf was conjugated to PAH via amide covalent linkages, and Tf-PAH coated the surface of DTX-loaded GO through electrostatic interactions. The morphology and structure of the resulting nanostructure, along with its surface modifications, were verified by use of Fourier transform infrared (FT-IR) and UV-vis spectroscopy, atomic force microscopy (AFM), and scanning electron microscopy (SEM). DTX was loaded at a relatively high loading capacity of 37% and released in a pH-dependent and sustained manner under physiological conditions. The targeting efficiency and cytotoxicity of this drug delivery system were evaluated on MCF-7 breast cancer cells. Improved efficacy of targeted DTX-loaded nanocarrier was observed compared to nontargeted carrier and free DTX, especially at high drug concentrations. The Tf-PAH-functionalized GO nanocarrier is a promising candidate for targeted delivery and controlled release of DTX.

Recent Advances in Targeted Tumor Chemotherapy Based on Smart Nanomedicines

“…The targeting efficiency was evaluated against MCF‐7 breast tumor cells. In contrast to free DTX that showed low cytotoxicity at a high DTX concentration, improved cytotoxicity of Tf‐modified DTX nanomedicine was observed as a result of the targeting effect and enhanced stability in cell medium . As aforementioned, drug delivery mediated by positive targeting initially relies on the passive targeting, which suggests that the positive and passive drug delivery mechanisms are interrelated.…”

“…In contrast to free DTX that showed low cytotoxicity at a high DTX concentration, improved cytotoxicity of Tf-modified DTX nanomedicine was observed as a result of the targeting effect and enhanced stability in cell medium. [40] As aforementioned, drug delivery mediated by positive targeting initially relies on the passive targeting, [22] which suggests that the positive and passive drug delivery mechanisms are interrelated. Adopting Tf as the positive targeting group (Figure 3), Singh et al found both the passive targeting and positive targeting exhibited dose-dependent therapeutic distinction.…”

Carbon Nanomaterials for Breast Cancer Treatment

“…This would allow for reducing the drugs dosage, their concentrations on sites that are not of interest, and the side effects associated with chemotherapy and hormonal therapy [15,16]. In this regard, carbon nanomaterials with potential uses for the administration of drugs against cancer and breast cancer are being analyzed [17,22,23,[29][30][31]; they are considered as advantageous systems to control drug release in the organism and increase the efficiency of treatments and reduce their toxicity [17,32,33]. However, carbon nanomaterials have some disadvantages including their lack of solubility and low reproduction rate through their chemical functionalization and structural characterization.…”

“…Many properties of carbon nanomaterials, such as size, shape, surface structure and charge, chemical composition, aggregation and/or agglomeration, and solubility, can greatly influence their interactions with biomolecules and cells. For example, carbon nanomaterials have been employed to produce exceptional images of tumor sites [20,21], impressive potential as high-efficiency delivery transporters for drugs and/or biomolecules into cells [20,22,23]. Therefore, the main emphasis of this article focuses on the discussion of carbon nanomaterials and their current applications in the identification, diagnosis, and treatment of breast cancer.…”

Incorporation of Graphene Quantum Dots, Iron, and Doxorubicin in/on Ferritin Nanocages for Bimodal Imaging and Drug Delivery

“…The unique properties of graphene derivatives have made them attractive nanomaterials in drug delivery and biomaging . Among graphene derivatives, graphene quantum dots (GQDs) have minimum toxicity owing to their ultra‐small size (<10 nm) and oxygen functional groups in their structure .…”