Fabrication and Antitumor Mechanism of a Nanoparticle Drug Delivery System: Graphene Oxide/Chitosan Oligosaccharide/γ‐Polyglutamic Acid Composites for Anticancer Drug Delivery

Abstract

This study focused on the design of a novel pH responsive nanoparticle drug delivery system (NDDS) with high biocompatibility and water solubility. The designed system was used for doxorubicin (DOX) delivery at tumor sites in a controlled manner. These innovative nanoparticles are soluble in physiological solutions besides water. In this study, pretreated γ‐polyglutamic acid (γ‐PGA) aqueous solutions were loaded into composites of graphene oxide (GO) covalently linked with chitosan oligosaccharide (CO) to fabricate GO‐CO‐γ‐PGA via amidation. The characterizations of the synthesized samples were carried out by using fourier transform infrared spectrometer (FTIR), X‐ray photoelectron spectrometer (XPS), ultraviolet– visible spectrophotometer (UV‐Vis), transmission electron microscopy (TEM), atomic force microscope (AFM) and zeta potential. Furthermore, drug loading and release behaviors from GO‐CO‐γ‐PGA were studied. The DOX loading in the constructed nanocarriers (GO‐CO‐γ‐PGA‐DOX) resulted in controlled and sustained release. The results of cell experiments revealed that the synthesized composites, which were easily transferred into cells, showed low toxicity and exhibited excellent antitumor effect due to its good connection with DOX. In addition, the composite nanoparticles caused the cell cycle arrest of Hela cells at the G2/M phase. Western blot results indicated that GO‐CO‐γ‐PGA‐DOX downregulated the expression of Bcl‐2 protein but upregulated Bax protein expression, which triggered the release of cytochrome C (Cytc). This condition further activated caspase‐3, cleaved the substrate of poly ADP‐ribose polymerase (PARP), and caused cell apoptosis. These results demonstrated that GO‐CO‐γ‐PGA‐DOX induces apoptosis via the intrinsic mitochondrial apoptotic pathway. Hence GO‐CO‐γ‐PGA composites have promising application in the field of biomedicine.

Functionalized Graphene Oxide for Chemotherapeutic Drug Delivery and Cancer Treatment: A Promising Material in Nanomedicine

“…CS is an amino polysaccharide, a hydrophilic, biocompatible, non-toxic, and biodegradable polymer of glucosamine and acetylglucosamine [ 121 , 122 , 123 , 124 ]. CS has been reported to have broad applications, including in biomedicine, agriculture, water treatment, food packaging, dentistry, ophthalmology, catalysis, textiles, paper, and biotechnology [ 125 ].…”

“…The authors evaluated the GO–CO–γ-PGA composite for pH-dependent controlled release of DOX into HeLa cells. While the GO–CS–γ-PGA nano-drug composite exhibited noteworthy cytotoxicity to HeLa cells, no cytotoxicity against normal cell lines was observed [ 121 ].…”

Synthesis and Application of ZIF‐8 MOF Incorporated in a TiO2@Chitosan Nanocomposite as a Strong Nanocarrier for the Drug Delivery of Acyclovir

“…[1,2,3] Most of the drawbacks can be decreased by effective and appropriative drug delivery systems (DDSs). [4,5] Nanoparticles (NPs) exhibit remarkable attributes such as the ability to protect drug from environmental factors, increasing drug stability in the bloodstream, transmission of low-soluble drugs, increasing fusion into target tissues and cells, capability to cross the blood-brain-barrier, increasing bioavailability in oral medicines, decreasing drug toxicity, prolonging circulation times, and reducing dose required for patients. [6,7] For these reasons, interests in targeted drug delivery system based on nanoparticles have extensively grown in recent years.…”

“…[22] Titanium dioxide (TiO 2 ) NPs are important tools in nanotechnology as pharmaceutical compounds, as well as attractive candidates for delivering many small drug molecules or large biomolecules such as DNA, RNA, and proteins. [23][24][25][26][27] Chitosan is a biocompatible polymer possessing several benefits such as low allergen city biodegradability, good solubility in acidic solution, and nontoxicity, [28][29][30][31][32] which is why it has been widely used in medicine, industry, wastewater treatment, and agriculture.…”

“…Although different drugs are versatile tools for the cure of intense sicknesses including cancer, Parkinson and cardiovascular diseases, they illustrate considerable disadvantages such as poor solubility and nonselective biodistribution, leading to toxicity damages to healthy tissues [1,2,3] . Most of the drawbacks can be decreased by effective and appropriative drug delivery systems (DDSs) [4,5] …”