Stimuli-Responsive Hydrogels for Cancer Treatment: The Role of pH, Light, Ionic Strength and Magnetic Field

Abstract

Cancer remains as the second leading cause of death, worldwide. Despite the enormous important advances observed in the last decades, advanced stages of the disease remain incurable. The severe side effects associated to systemic high doses of chemotherapy and the development of drug resistance impairs a safe and efficiency anticancer therapy. Therefore, new formulations are continuously under research and development to improve anticancer drugs therapeutic index through localized delivery at tumor sites. Among a wide range of possibilities, hydrogels have recently gained special attention due to their potential to allow in situ sustained and controlled anticancer drug release. In particular, stimuli-responsive hydrogels which are able to change their physical state from liquid to gel accordingly to external factors such as temperature, pH, light, ionic strength, and magnetic field, among others. Some of these formulations presented promising results for the localized control and treatment of cancer. The present work aims to discuss the main properties and application of stimuli-responsive hydrogels in cancer treatment and summarize the most important advances observed in the last decades focusing on the use of pH-, light-, ionic strength-, and magnetic-responsive hydrogels.

Hydrogel-By-Design: Smart Delivery System for Cancer Immunotherapy

“…Those hydrogels with stimulus-responsive properties can be used as a drug delivery system in cancer immunotherapy, in which drug release is triggered upon external stimulis ( Bajpai et al, 2008 ; Andrade et al, 2021 ) such as pH, temperature, and biomolecule concentration ( Figure 2D ). The cross-linking process of the hydrogel can respond to external stimuli.…”

“…The swelling behaviour of hydrogels can be affected by various external physicochemical conditions, which have been widely exploited in controlled drug delivery. pH responsive swelling is particularly important for cancer delivery systems because it allows targeted drug release in solid tumors where tumour microenvironments are typically more acidic than normal tissues ( Andrade et al, 2021 ). Other stimuli responsive swelling mechanisms have also been exploited for controlled drug delivery.…”

“…Moreover, hydrogels respond immediately to various external stimuli and undergo morphological changes, which realize sustained and controlled release of therapeutics for cancer immunotherapy ( Lin and Metters, 2006 ; Ma et al, 2021 ). Novel pH-responsive hydrogels with high swelling property at acidic pH were shown to release drug at a relative fast rate by adjusting the ratio of chitosan and alginate polymers with poly (vinyl alcohol) ( Andrade et al, 2021 ). In addition, the advantages of ease of synthesis, and low raw material prices also make hydrogels a very promising delivery agent for multiple immunological therapeutics ( Ahmed, 2015 ).…”

Multifunctional and Self-Healable Intelligent Hydrogels for Cancer Drug Delivery and Promoting Tissue Regeneration In Vivo

“…Natural hydrogels have widely been used as drug delivery vehicles such as HA, collagen, gelatin, alginate, chitosan [ 36 ]. Hydrogels based on different parameters can be classified based on network size (macrogels, microgels, nanogels), composition (homo or copolymeric), electrical charge (non-ionic, cationic, anionic, amphoteric, or zwitterionic), crosslinking (physical or chemical) [ 37 ]. Some hydrogels can provide a response to an environmental stimulus such as ionic force or pressure, temperature, pH, and light which reflect to their structure [ 37 ].…”

Metronomic Anti-Cancer Therapy: A Multimodal Therapy Governed by the Tumor Microenvironment

“…Several drug-delivery systems, such as drug depots [230][231][232], hydrogels [233][234][235][236], microspheres [237,238], or nanocarriers (NCs) [239,240], have been developed and investigated. For intra-tumoral drug delivery and for bypassing physiological barriers, local drug-loaded depots and hydrogels have allowed the long-term delivery of treatment at the site of action [234,241].…”