Recent Advancements in Stimuli Responsive Drug Delivery Platforms for Active and Passive Cancer Targeting

Simple Summary Cancer is one of the leading causes of death globally. Several studies, efforts and treatment strategies have been put forth for the treatment of different types of cancers. Several chemotherapeutic agents have been discovered and utilized for the treatment of various types of cancers and tumors, which play an important role in improving the quality of life of patients. The key problems associated with the abovementioned chemotherapeutic agents are the limited target ability and non-selective toxicity. The current review focuses on the achievement of improved targeting of anticancer agents at the tumor microenvironment without affecting normal tissues. The fulfilment of the mentioned objectives by stimuli-responsive drug delivery systems, as physical stimuli-responsive drug delivery systems and chemical stimuli-responsive drug delivery systems through active and passive targeting have extensively been discussed in the current review. The current review will help the wide community of researchers conducting research in targeted drug delivery systems and anticancer treatment strategies. The tumor-specific targeting of chemotherapeutic agents for specific necrosis of cancer cells without affecting the normal cells poses a great challenge for researchers and scientists. Though extensive research has been carried out to investigate chemotherapy-based targeted drug delivery, the identification of the most promising strategy capable of bypassing non-specific cytotoxicity is still a major concern. Recent advancements in the arena of onco-targeted therapies have enabled safe and effective tumor-specific localization through stimuli-responsive drug delivery systems. Owing to their promising characteristic features, stimuli-responsive drug delivery platforms have revolutionized the chemotherapy-based treatments with added benefits of enhanced bioavailability and selective cytotoxicity of cancer cells compared to the conventional modalities. The insensitivity of stimuli-responsive drug delivery platforms when exposed to normal cells prevents the release of cytotoxic drugs into the normal cells and therefore alleviates the off-target events associated with chemotherapy. Contrastingly, they showed amplified sensitivity and triggered release of chemotherapeutic payload when internalized into the tumor microenvironment causing maximum cytotoxic responses and the induction of cancer cell necrosis. This review focuses on the physical stimuli-responsive drug delivery systems and chemical stimuli-responsive drug delivery systems for triggered cancer chemotherapy through active and/or passive targeting. Moreover, the review also provided a brief insight into the molecular dynamic simulations associated with stimuli-based tumor targeting.