Hydrogels as cancer theranostic platforms

Abstract

Theranostic hydrogels combine cancer therapy and diagnostics on a single platform. Hydrogels are water-absorbing polymer networks that can embed drugs and imaging agents inside their structure. Stimuli-responsive hydrogels can release the embedded agents in response to stimuli. For example, pH, temperature, ultrasound, light, and magnetic field can initiate the swelling of stimuli-responsive hydrogels and thus induce the release of different agents. The structural changes of Schiff base bonds or ionizable groups give rise to the swelling of pH-sensitive hydrogels. Since the tumor environment is acidic, pH-sensitive hydrogels are often utilized in cancer treatment. Temperature-sensitive hydrogels are based on polymers that can transform from solution state to gel state in response to temperature variation. As for the ultrasound, it can inflict the release of drugs and imaging agents indirectly by producing an increase in temperature and pressure. Light sensitivity can be achieved by adding functional groups to the polymer network that can go through cis-trans-isomerization or other structural changes in response to light. While magnetic particles inside the hydrogel cause sensitivity to the magnetic field.

Hydrogels can be delivered to the body environment in different ways. The injection of hydrogels is one of the most common delivery strategies since it is minimally invasive and enables the transportation of the hydrogel to various body parts. In order to have a successful injection, hydrogels must have suitable properties for gelling. In addition to injections, hydrogels can be delivered orally to treat gastric and colon cancer. Orally delivered hydrogels must be durable because they have to endure the enzymatic and acidic conditions of the digestive tract. Pulmonary delivery enables the treatment of lung cancer via inhalation of the hydrogel. Whereas the nose cavity provides a great position for brain cancer treatment. Similar to the digestive tract, also respiratory tract is covered by mucous membrane, and therefore the bioadhesive properties of hydrogels are especially important. In the case of melanoma treatment, hydrogel-based microneedle patches have shown excellent results. Hydrogels can be also surgically implanted but due to the invasiveness of the operation, hydrogel implantation is usually only utilized when it is combined with compulsory surgery.

Theranostic hydrogels are embedded with imaging agents. For some diagnostic techniques, the imaging agents are a necessity, whereas for some techniques their task is only to improve the accuracy by enhancing the signals. Imaging agents can accumulate in tumors, or they can remain in the hydrogel and thus provide information on the hydrogel degradation. In addition to hydrogel degradation, theranostic hydrogels can also gather information on drug distribution, cancer progression, tumor size, and effectiveness of the treatment. Diagnostic imaging can be performed for example by magnetic resonance imaging and optical imaging. This work intends to offer information on theranostic hydrogels in cancer treatment and introduce the reader to the essential aspects that need to be considered in their development.