Stimuli‐Responsive Prodrug Chemistries for Cancer Therapy

Abstract

Prodrugs are pharmacologically inactive, chemically modified derivatives of active drugs, which, following in vivo administration, is converted to the parent drugs through chemical or enzymatic cleavage. The prodrug approach holds tremendous potential to create the enhanced version of an existing pharmacological agent and leverage those improvements to augment the drug molecules' bioavailability, targeting ability, therapeutic‐efficacy, safety, and marketability. Especially in cancer therapy, prodrug application has received substantial attention. A prodrug can effectively broaden the therapeutic window of its parent drug by enhancing its release at targeted tumor‐sites while reducing its access to healthy cells. The spatiotemporally controlled‐release can be achieved by manipulating the chemical, physical, or biological stimuli present at the targeted tumor site. The critical strategy comprises of drug‐carrier linkages that respond to physiological or biochemical stimuli in the tumor milieu to yield the active drug form. This review will focus on the recent advancements in development of various fluorophore‐drug conjugates that are widely used for real‐time monitoring of drug delivery. The use of different stimuli‐cleavable linkers and the mechanisms of linker cleavage will be discussed. Finally, the review will conclude with a critical discussion on the prospects and challenges that might impede the future development of such prodrugs.

Ultrasound-Controlled Prodrug Activation: Emerging Strategies in Polymer Mechanochemistry and Sonodynamic Therapy

“…Since its first introduction in 1958, the prodrug concept has paved the way for tailored drug delivery systems spanning diverse fields from cancer treatments to antiviral therapeutics. Notably, physical stimuli-responsive prodrugs, especially those regulated by external stimuli such as light and ultrasound, have attracted significant attention due to their real-time control over drug activation with spatiotemporal precision. , Ultrasound refers to mechanical sound waves beyond human hearing (20 kHz to MHz range). In comparison to light-based therapies, a notable advantage of ultrasound as a stimulus is its ability to penetrate tissues without the requirement for optical transparency in the medium, rendering ultrasound advantageous for deep tissue imaging, diagnostics, and therapeutic interventions. , …”

Research Progress of Disulfide Bond Based Tumor Microenvironment Targeted Drug Delivery System

“…The selective release of nanomedicine at the target site is crucial for the effectiveness and safety of the drug. 12 , 13 Due to the rapid proliferation and growth of tumors, it has a series of special microenvironments such as low oxygen, slightly acidic, high oxidative stress, high concentration of GSH, and overexpression of some enzymes. 14 In recent years, based on these special characteristics of the tumor microenvironment, different stimulus-responsive nanomedicine have been developed and applied in cancer therapy.…”