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Tumor-targeting Dendrimers—a Nanotechnology based Cancer Therapy

cancer

 

Cancer remains as one of the leading causes of death worldwide, and millions of dollars are being invested into cancer research. Over the years, cancer treatment has expanded to include methods such as surgery, radiation therapy, chemotherapy, stem cell transplant, and most recently immunotherapy. With chemotherapy in particular, the patients often experience severe side effects like hair loss, kidney damage, and infection in response to the toxicity of the drugs. This toxicity generally occurs when the chemotherapeutic agents attack normal cells. Chemotherapy is administered in a way that is not tumor-specific, and usually the drug ends up being distributed throughout the body. In order for chemotherapy to be more efficient, there is need for a drug delivery system that will be specific in only targeting tumor cells. Nanoparticles have surfaced as a possible delivery system that can do just that.

Nanoparticles have the potential to improve the transport and effectiveness of cancer drugs because their size affects how a drug is distributed throughout the body and delivered to a tumor site. Their size aids in targeting tumors through the enhanced permeability and retention effect (EPR effect), which allows the nanoparticles to accumulate into tumor tissue as opposed to normal tissue (as shown in the figure above), reducing the side effects of the drug.More so, the nanoparticles can be designed for multiple functions by decorating them with tree-like molecules called dendrons and terminating the dendrons with different chemotherapeutic drugs, imaging dyes, and targeting agents. These dendrons are then combined around a central nanoparticle to form a multifunctional dendrimer.

My project involves making gold nanoparticle-cored dendrimers and terminating them with the chemotherapeutic agent cisplatin. Cisplatin is a common drug that is known to treat the following: non-small cell lung cancer, bladder cancer, cervical cancer, ovarian cancer, head and neck cancer, and testicular cancer. To create these dendrimers, the dendrons are first synthesized and attached to a spacer molecule that helps reduce steric hindrance when coupling dendrons with the gold nanoparticles (GNPs). The cisplatin drug molecules are then added to the ends of the dendrons through a cleavable bond to allow for specific release into tumor cells. The completed dendrons are then attached to the GNPs to create the dendrimers. These dendrimers will be more specific in delivering cisplatin to the tumor sites, making the drug less toxic to normal tissues and more efficient.