Abstract

Simple SummaryCancer 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.

Highlights

  • Cancer remains one of the leading causes of death globally

  • Electroporation is an efficient pathway for electro-responsive drug delivery which involves the application of a high voltage across the membrane to cause the formation of pores in cell membranes, increasing their permeability to drugs [74]

  • Enhanced tumor-specific cytotoxicity, cell uptake and synergistic effects of biological and magnetic field-assisted targeting by magnetic field responsive liposomes relative to non-magnetic liposomes

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Summary

Introduction

Cancer remains one of the leading causes of death globally. Each year more than eight million people die of cancer worldwide [1]. Among the aforementioned drug delivery strategies, stimuli-responsive lipid-based drug delivery systems, nanocarriers and prodrugs as displayed, have attained the greatest attention. These drug delivery systems have the imperative attributes which include enhanced selectivity, biocompatibility, cancer microenvironmentbased sensitivity and clinical acceptance with added benefits of easy scale up and multiple options regarding the choice and selection of formulation components. Drug delivery systems through stimuli-responsive carriers, lipids and/or prodrugs in the tumor milieu can lead to accelerated/triggered drug release at the target site, improved cellular binding and internalization, or more effective drug perfusion throughout the tumor volume [16].

Stimuli-Responsive Drug Delivery Systems
Thermoresponsive Drug Delivery Systems
Stimuli-Responsive Lipids
Major Findings
Chemical Stimuli-Responsive Drug Delivery Systems
Enzymes-Responsive Drug Delivery Systems
Stimuli-Responsive Prodrugs
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