Hyaluronic acid and Arg-Gly-Asp peptide modified Graphene oxide with dual receptor-targeting function for cancer therapy

Abstract

Graphene oxide (GO) modified with hyaluronic acid (HA) and Arg-gly-asp peptide (RGD) was designed as a dual-receptor targeting drug delivery system to enhance the specificity and efficiency of anticancer drug delivery. Firstly, GO-HA-RGD conjugate was characterized to reveal its structure and morphology. Whereafter, doxorubicin (Dox) as a model drug was loaded on GO-HA-RGD carrier, which displayed a high loading rate (72.9%, GO:Dox (w/w) = 1:1), pH-response and sustained drug release behavior. Cytotoxicity experiments showed that GO-HA-RGD possessed excellent biocompatibility towards SKOV-3 and HOSEpiC cells. Additionally, the GO-HA-RGD/Dox had a stronger cytotoxicity for SKOV-3 cells than either GO-HA/Dox (single receptor) or GO/Dox (no receptor). Moreover, celluar uptake studies illustrated that GO-HA-RGD conjugate could be effectively taken up by SKOV-3 cells via a synergic effect of CD44-HA and integrin-RGD mediated endocytosis. Hence, GO-HA-RGD nanocarrier is able to be a promising platform for targeted cancer therapeutic.

Mechanistic Insight on the Interaction between OPN and Integrin ανβ3 in Osteoarthritis

“…This interaction regulates the expression of tumor-related proteins during carcinogenesis in patients with rectal and/or lung cancer [ 29 , 30 ]. Moreover, integrin interacts with HA to modulate differentiation and metastasis of tumor cells [ 31 , 32 ], suggesting a mechanism involving the stimulation of downstream effects upon OPN and integrin receptor interaction. This includes extracellular signaling and regulation of HA synthesis, thereby affecting the development of OA.…”

Oxidized graphene nanoparticles as a delivery system for the pro‐apoptotic sphingolipid C6 ceramide

“…Such modified forms of graphene can include materials such as iron oxide nanoparticles, polypyrrole, and silver nanoparticles, and the combination of these materials with graphene oxide can be induced to release more drug loaded onto them through the external application of stimuli such as magnetic fields, electricity, and near‐infrared light, respectively . Graphene can also be functionalized with a wide variety of materials that would allow for the specific targeting of cancer cells, including folic acid, antibodies, and RGD peptides . Such modifications can not only enable higher effective doses of drug delivered to cancer cells, but can also reduce the toxicity to surrounding healthy tissue caused by nonspecific delivery.…”

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

“…Guo et al developed a dual-receptor-targeting drug delivery system, in which GO was functionalized with HA via ADH linker, and further with Arg–Gly–Asp peptide (RGD) for targeted drug delivery with more selectivity and specificity [ 156 ]. The synthesis first involves the modification of HA with ADH to introduce an amino group on the HA’s surface.…”

“…Cellular uptake study revealed higher cellular uptake of GO–HA–RGD–DOX compared to GO–HA–DOX or GO–DOX systems. This specific dual targeting ability was achieved through the combined effect of the CD44–HA receptor, and integrin–RGD-facilitated endocytosis [ 156 ].…”