PolyPEGylated nanodiamond for intracellular delivery of a chemotherapeutic drug

Abstract

Water dispersible and biocompatible polyPEGylated ND nanoparticles were prepared via surface-initiated atom transfer radical polymerization. Cell internalization study reveals that ND nanoparticles facilitate the transport of doxorubicin hydrochloride into A549 cells, indicating their potential applications in cancer therapy.Over the past few decades, carbon nanomaterials (CNMs) have attracted a great deal of scientific and technological attention due to their unique structure and remarkable electronic, mechanical and thermal properties. These materials have shown promising applications in different fields such as electronics, energy conversion and storage, and biomedicine etc. 1-6 Nanodiamond (ND) is a relative new class of CNM, which has been investigated extensively for biomedical applications in recent years due to its excellent physicochemical properties, biocompatibility, inexpensive large scale synthesis and small size (2-10 nm). 7-18 It has been reported that fluorescent ND nanoparticles could be used as bioprobes for single particle tracing in cells and even in small organisms such as Caenorhabditis elegans. [19][20][21] It has also been suggested that ND might be useful for controlled drug delivery and gene therapy as well as tissue engineering. 22-26 For many of these biomedical applications, effective dispersion of ND in aqueous solution especially in physiological solution is necessary. On the other hand, like many other nanomaterials, ND nanoparticles are readily recognized as foreigners by the mononuclear phagocytic system (MPS) of cells and are rapidly cleared from blood circulation after intravenous administration, resulting in cumulative negative effects on the MPS and leading to impairment of this vital host defence system. 27-31 Therefore, effective dispersion of ND in aqueous media and preventing it from recognition by the MPS are crucial for the practical biomedical applications of ND.Polyethylene glycol (PEG) is a class of hydrophilic polymer with outstanding physicochemical and biological properties, such as excellent water-solubility and biocompatibility. 32,33 The conjugation of PEG chains on the nanoparticle surface (PEGylation) is expected to render nanoparticle dispersion as well as reduce protein opsonization and subsequent phagocytosis by MPS to the nanoparticles, which can help these PEGylated nanoparticles escape from the reticuloendothelial system (RES) after intravenous administration. To date, PEGylation of many nanoparticles, such as liposome, quantum dots, gold nanoparticles, carbon nanotubes and other nanomaterials could extremely reduce the nanoparticles' uptake by MPS and prolong their blood circulation time. [34][35][36][37][38] Our previous study has demonstrated that PEG or polyPEGMA molecules could be immobilized onto the surface of ND via both ''grafting to'' and ''grafting from'' methods. 39 The polyPEGMA conjugated ND showed enhanced dispersibility in both aqueous and organic media.In current work, we present the polyPEGylation of ND through surface-initiated atom t...

Smart pH-responsive and high doxorubicin loading nanodiamond for in vivo selective targeting, imaging, and enhancement of anticancer therapy

“…[36][37][38][39] Therefore, PEG has been introduced to the ND, which can not only improve the dispersion, but also reduce the interaction with cells to reducing non-specific effects, and prolong the blood circulation time. [40][41] We have prepared ND-PEG via an ester band and found that PEGylated ND showed enhanced dispersity and stability in vitro under the physiological environment or in cell culture medium in our previous study. 42 Unfortunately, the Taking into account the necessity of high drug loading, augmented treatment efficiency and targeting ability for tumor, a novel nanodrug based on free DOX physical adsorption onto PEGylated ND in sodium citrate medium was designed (Scheme 1).…”

Preparation of amine functionalized carbon nanotubes via a bioinspired strategy and their application in Cu2+ removal

“…As compared with the pristine CNTs, the funcitonalized CNTs have demonstrated to be better performance in heavy metal ion removal [17,18]. Previously, a number of surface modification strategies such as surface oxidation with concentrated acid, non-covalent with surfactants and amphiphilic polymers, in situ polymerization and hybridized with inorganic nanomaterials have been reported [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. On the other hand, different physical methods such as plasma irradiation and gamma-irradiation have also developed for surface modification of CNTs.…”

PEGylation of carbon nanotubes via mussel inspired chemistry: Preparation, characterization and biocompatibility evaluation

“…For example, we have previously demonstrated that PEGylation of nanodiamonds could be achieved through both graft to method and graft from method [54]. These PEGylated nanodiamonds showed high water dispersibiliy and can be used for intracellular delivery of anticancer drug (DOX) into cells with good performance [60]. More importantly, PEGylation is also an important strategy for avoiding nanomaterials swallowed by reticuloendothelial system in vivo, which is very useful for improving the therapeutic index and decreasing the adverse effects of drugs [59].…”

“…The cell viability was further used to quantitatively evaluate the biocompatibility of CNT-PDA-PEGMA using the WST assay as described in our previous reports [51][52][53]. Briefly, cells were seeded in 96-well microplates at a density of 5 × 10 4 cells per mL in 160 L Then the cells were washed with PBS for three times to remove the uninternalized nanoparticles.…”