Glutathione‐Responsive Nanoparticles of Camptothecin Prodrug for Cancer Therapy

Abstract

Camptothecin (CPT) is a potent chemotherapeutic agent for various cancers, but the broader application of CPT is still hindered by its poor bioavailability and systemic toxicity. Here, a prodrug that releases CPT in response to glutathione (GSH), which is commonly overexpressed by cancer cells is reported. Through assembling with PEGylated lipids, the prodrug is incorporated within as‐assembled nanoparticles, affording CPT with a prolonged half‐life in blood circulation, enhanced tumor targetingability, and improved therapeutic efficacy. Furthermore, such prodrug nanoparticles can also promote dendritic cell maturation and tumor infiltration of CD8 + T cells, providing a novel strategy to improve the therapeutic efficacy of CPT.

Selenization of Small Molecule Drugs: A New Player on the Board

“…Notwithstanding, its broader therapeutic application is hindered by several poor clinical outcomes ascribed to this drug such as low bioavailability and systemic toxicity. In this regard, various modifications of CPT have been reported in the last years. − A wide range of chemical moieties have been conjugated at the hydroxy group in the α position of the lactone functional group to improve its antitumoral effects. − Interestingly, two Se prodrugs ( 27 and 28 ) (Figure ) have been synthesized by the introduction of a diselenide moiety in this drug structure and have exhibited significantly higher cytotoxic effects to different cancer cell lines compared to CPT (Table ). Furthermore, these CPT analogues unveiled efficient in vivo antitumoral activities and good tolerance in a mouse model compared to the parent drug …”

Camptothecin-based prodrug nanomedicines for cancer therapy

“…To circumvent these limitations, Zhang and coworkers fabricated GSH-responsive nanoprodrugs of S-NP-CPT for cancer therapy relying on the abovementioned carbonate-disulfide linkage. 40 S-NP-CPT was synthesized via the conversion of the α-hydroxyl group of stearic acid (SA) to a disulfide-containing stearic ester, which could react with CPT via triphosgene-catalyzed ligation to form the carbonate-disulfide-linked CPT prodrug of CPT-SS-SA (Fig. 1A).…”

Self‐Propelled Enzymatic Nanomotors from Prodrug‐Skeletal Zeolitic Imidazolate Frameworks for Boosting Multimodel Cancer Therapy Efficiency

“…[27] In order to enabling the PDT efficacy, many researches have been devoted for the 1 O 2 augmentation through direct carrying or in situ generation of O 2 in tumor tissues, or the GSH depletion to block their consumption. [28][29][30] Intriguingly, CAT-engineered micro/nanomotors can consume overproduced endogenous hydrogen peroxide (H 2 O 2 , about 100 × 10 −6 to 1 × 10 −3 m) in tumor cells to generate oxygen (O 2 ) for their self-propulsion. Meanwhile, the supplied O 2 species can further enable the O 2 -dependent PDT therapy through reversing the tumor hypoxia surroundings.…”