Biofunctionalized Nanosheet Strengthens Antitumor Targeting

Biofunctionalized nanosheet enhances antitumor targeting

Scientists have recently developed a biofunctionalized graphene oxide (GO) nanoplatform, with high drug loading capacity and controllable drug release, for amplified antitumor therapy. This study was published as a pre-trial in Biomaterials.

Study: Biofunctionalized graphene oxide nanosheet to amplify antitumor therapy: high multimodal drug encapsulation, prolonged hyperthermal window and deep burst drug release. Image Credit: Mopic/Shutterstock.com

Graphene and its derivatives as nanocarriers and therapeutic agents

Graphene is a type of sp2-hybridized carbon nanoparticle. 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 derivatives of graphene, such as graphene oxide (GO) and reduced graphene oxide (rGO) exhibit plasmonic properties, which can convert laser energy into heat. These carbon nanoparticles have been applied in various biomedical applications, including magnetic hyperthermia therapy (MHT), photodynamic therapy (PDT), sonodynamic therapy (SDT), and photothermal therapy (PTT).

Recently, researchers reported that graphene quantum dots (GQDs) were used as PTT and PDT agents for cancer imaging and treatment. As graphene and its derivatives can absorb intense near-infrared (NIR) light, GO-inspired PTT has been applied for tumor ablation.

Previous studies revealed that GO nanosheets are favorable nanocarriers to charge and deliver multiple molecules of hydrophobic photosensitizers. One of the main advantages of the nanocarrier based on GO nanosheets is the dual capacity, i.e. to deliver drugs without aggregation in physiological solutions and superior therapeutic effects via the combination of PTT and PDT.

Despite several advantages, one of the limitations of using GO nanosheets is that they contain large surface areas, allowing for a higher protein absorption rate. This leads to the formation of “protein crowns” when in contact with biological media and inhibits tumor targeting.

The researchers stated that a multifunctional GO-mediated drug depot must be designed to achieve optimal efficiency of thermo-chemotherapy and address these issues. In this context, they used an artificial surface function assembly of GO nanoparticles for drug delivery and treatment.

Designing GO-Based Nanomedical Systems – A New Study

To improve nanomedical systems, scientists have used the corona protein to optimize biological (eg, tumor) recognition, thereby improving the efficiency of targeted drug delivery. Based on the existing literature, endogenous apolipoprotein AI (apoA-I) with its natural ability to scavenge receptor-type BI (SR-BI) overexpressed tumor cells, as well as its ability to evade elimination from the system reticuloendothelial, could be exploited for the fabrication of a nanoplatform for antitumor therapy. Importantly, 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, to apoA-I could benefit nanoparticles upon drug delivery due to its high transvascular extravasation. Moreover, it also exhibited specific tumor penetration by sequential recognition of neuropilin-1 (NRP-1) and αvβ3/5 integrin.

In the current study, scientists designed a biomimetic GO nanoplatform, based on iRGD-conjugated apoA-I protein (iRGD-apoA-I), with superior tumor targeting ability, biological stability, and high penetrating ability to amplify thermo-chemotherapy.

The protein crown was tightly bound to the GO nanosheet (iAPG) via electron-deficient PBA fragments. The biofunctionalized GO nanosheets were fixed with an iRGD-apoA-I crown in a stable and controlled manner. Doxorubicin (DOX) molecules were trapped like a sandwich in the GO reservoir 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 ability due to the influence of iAPG. Moreover, it also enables photothermal conversion and induces the triggered release of DOX via extra or intra-cellular stimuli.

Scientists reported that after NIR irradiation, the iRGD-apoA-I crown allows longer heat retention of GO, which is attributed to its high efficiency 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 cellular internalization.

This hypothesis was validated by experimental studies and revealed that iAPG/DOX did not interact with serum proteins. Additionally, the authors reported improved cargo accumulation and entry into targeted tumor sites.

In situ studies have revealed that NIR irradiation can disrupt endo/lysosomal membranes for the release of bursts of DOX. Moreover, the iAPG structure exhibited significant photothermal transformation and was able to deliver DOX into tumor cells upon exposure to NIR irradiation. Therefore, this approach was found to be able to effectively limit tumor growth and metastasis during NIR irradiation. This strategy provided synergistic thermochemotherapy without causing peritumoral damage.

Final remarks​​​​​​​

The authors said their biofunctionalized GO nanosheet based on engineered proteins increased the scope of carbon nanoparticles in biomedical applications. The new nano-based drug depot with improved hyperthermal window, multimodal drug encapsulation and fast-release drug could be effectively applied in anti-tumor therapy.

Reference

Wang, Z et al. (2022) Biofunctionalized graphene oxide nanosheet to amplify antitumor therapy: high multimodal drug encapsulation, prolonged hyperthermic window, and deep burst drug release. Biomaterials. https://www.sciencedirect.com/science/article/pii/S0142961222002691?via%3Dihub

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