Scientists have recently designed a biofunctionalized graphene oxide (GO) nanoplatform, with high drug loading capacity and controllable drug release, for amplified antitumor therapy. This study has been published as a preliminary test in Biomaterials.
Study: Biofunctionalized graphene oxide nanoflower to amplify antitumor therapy: multimodal encapsulation of elevated drugs, prolonged hyperthermic window, and release of explosive drugs at a deep site. Image credit: Mopic / Shutterstock.com
Graphene and its derivatives as nanocarriers and therapeutic agents
Graphene is a type of carbon nanoparticle with sp2 hybridization. This two-dimensional (2D) structure is used in multiple applications, including biomedical research. Graphene nanosheet contains several active sites and provides suitable conditions for reactions (e.g., conjugation reactions) with functional groups.
Some of the graphene derivatives, such as graphene oxide (GO) and reduced graphene oxide (rGO) have plasmonic properties, which can transform the energy of a laser into heat. These carbon nanoparticles have been applied in several biomedical applications, including magnetic hyperthermia therapy (MHT), photodynamic therapy (PDT), sonodynamic therapy (SDT), and photothermal therapy (PTT).
Researchers have recently reported that graphene quantum dots (GQDs) were used as PTT and PDT agents for cancer imaging and treatment. Because graphene and its derivatives can absorb near-infrared light (NIR), GO-inspired PTT has been applied for tumor ablation.
Previous studies have shown that GO nanosheets are favorable nanoparticles for loading and delivering multiple hydrophobic photosensitizing molecules. One of the key advantages of GO nanosheet-based nanocarrier is the dual capability of delivering drugs without aggregation in physiological solutions and superior therapeutic effects through the combination of PTT and PDT.
Despite several advantages, one of the limitations of the use of GO nanosheets is that it contains large surfaces, allowing a higher rate of protein absorption. This leads to the formation of “protein crown” when in contact with biological media and inhibits tumor orientation.
The researchers stated that a GO-mediated multifunctional drug repository should be designed to achieve optimal efficacy of thermo-chemotherapy and solve these problems. In this context, they used an artificial nanoparticle surface function assembly of GO nanoparticle for drug delivery and treatment.
Design of GO-based nanomedical systems – A new study
To improve nanomedical systems, scientists have used corona protein to optimize biological recognition (e.g., tumor), thereby improving the efficiency of drug delivery to the target. Based on the existing literature, the endogenous AI apolipoprotein (apoA-I) with its natural ability to remove overexpressed BI receptor-type tumor cells (SR-BI), along with its ability to escape elimination of the reticuloendothelial system could be exploited for the manufacture of nanoplatforms for antitumor therapy. It is important to note that the apoA-I-forming protein crown exhibits a bioconjugation reaction.
A previous study found that conjugation of iRGD (CRGDKGPDC), a 9-amino acid cyclic peptide, with apoA-I could benefit nanoparticles during drug delivery due to its high transvascular extravasation. In addition, it also showed specific tumor penetration by sequential recognition of neuropilin-1 (NRP-1) and αvβ3 / 5 integrin.
In the current study, the scientists designed a biomimetic GO nanoplatform, based on the iRGD-conjugated apoA-I protein (iRGD-apoA-I), with superior tumor targeting capacity, biological stability, and high penetration capacity. amplify thermo-chemotherapy.
The protein crown was strongly bound to GO nanosheet (iAPG) by electron-deficient PBA fragments. Biofunctionalized GO nanosheets were connected to an iRGD-apoA-I crown in a stable and controlled manner. Doxorubicin (DOX) molecules were trapped like a sandwich in the GO tank by dense π-π stacking, boron-nitrogen (BN) coordination, and hydrophobic interaction.
The introduction of the iRGD-apoA-I crown into the GO nanosheet showed remarkable drug encapsulation capacity due to the influence of iAPG. In addition, it also allows photothermal conversion and induces the activated release of DOX by extra or intracellular stimuli.
The scientists reported that after NIR irradiation, the iRGD-apoA-I crown allows for longer GO heat retention, which is attributed to its high efficacy in hyperthermic oncotherapy.
The researchers hypothesized that after administration of iAPG / DOX in humans, it would show greater biocompatibility and would not trigger immunogenic reactions in the blood, or after transvascular extravasation, tumor penetration, and cell internalization. lular.
This hypothesis was validated by experimental studies and revealed that iAPG / DOX did not interact with serum proteins. In addition, the authors reported an improvement in the accumulation and entry of loads at target tumor sites.
In situ studies revealed that NIR irradiation could disrupt endo / lysosomal membranes for DOX release. In addition, the iAPG structure showed significant photothermal transformation and was able to deliver DOX to tumor cells after exposure to NIR irradiation. Therefore, this approach was found to be able to effectively restrict tumor growth and metastasis with NIR irradiation. This strategy provided synergistic thermo-chemotherapy without causing peritumor damage.
Concluding remarks
The authors claimed that their engineered protein-based biofunctionalized GO nanosheet raised the reach of carbon nanoparticles in biomedical applications. The new nano-based drug repository with enhanced hyperthermic window, multimodal drug encapsulation, and blast-release drugs could be effectively applied in antitumor therapy.
Reference
Wang, Z. et al. (2022) Biofunctionalized graphene oxide nanoflower to amplify antitumor therapy: multimodal encapsulation of elevated drugs, prolonged hyperthermic window, and release of explosive drugs at a deep site. Biomaterials. https://www.sciencedirect.com/science/article/pii/S0142961222002691?via%3Dihub
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