Emerging Strategies in Stimuli-Responsive Prodrug Nanosystems for Cancer Therapy

Abstract

Prodrugs are chemically modified drug molecules that are inactive before administration. After administration, they are converted in situ to parent drugs and induce the mechanism of action. The development of prodrugs has upgraded conventional drug treatments in terms of bioavailability, targeting, and reduced side effects. Especially in cancer therapy, the application of prodrugs has achieved substantial therapeutic effects. From serendipitous discovery in the early stage to functional design with pertinence nowadays, the importance of prodrugs in drug design is self-evident. At present, studying stimuli-responsive activation mechanisms, regulating the stimuli intensity in vivo, and designing nanoscale prodrug formulations are the major strategies to promote the development of prodrugs. In this review, we provide an outlook of recent cutting-edge studies on stimuli-responsive prodrug nanosystems from these three aspects. We also discuss prospects and challenges in the future development of such prodrugs.

Lipid Prodrug Nanoassemblies via Dynamic Covalent Boronates

“…The chemical structure of Lipid-CIP was further proven by its corresponding MS spectra (Figure S13, Supporting Information). Besides, the absorbance peak at −26 ppm (boronic acid) disappeared, and a new peak at around 2 ppm (boronate ester) appeared in their corresponding 11 B NMR spectra (Figure 1c). In the subsequent Fourier transform infrared (FT-IR) spectroscopy (Figure S14, Supporting Information), the vibration peaks of BO−H and ArO−H were replaced by the peaks of ArO−B.…”

“…In this regard, prodrug nanoassemblies are formed. Prodrugs refer to the covalently modified drugs that can release the active parent drug in vivo via enzymatic and/or chemical transformation. ,, However, the clinical application of prodrug nanoassemblies is often limited by their laborious synthesis, low manufacturing scales, and low drug-loading content (DLC).…”

Pillararene-Based Supramolecular Polymers for Cancer Therapy

“…Cancer has become one of the “biggest killers” of human beings worldwide [ 1 , 2 , 3 , 4 , 5 ]. Cancer poses a threat to human health, claiming millions of lives each year [ 6 , 7 , 8 , 9 , 10 ].…”

Near-Infrared-Activatable PROTAC Nanocages for Controllable Target Protein Degradation and On-Demand Antitumor Therapy

“…14 By contrast, exogenous stimuli enable a more precise control of drug release in an on-demand manner. 15 As a noninvasive exogenous stimulus, light has been widely used in the fields of optogenetics and photocontrolled drug delivery. 16−18 Recently, the photocaged 19−21 and photoswitchable PROTACs were reported, 22 which provided a light-controllable technique to spatiotemporally regulate protein degradation.…”