Smart stimuli-responsive carrier-free nanoassembly of SN38 prodrug as efficient chemotherapeutic nanomedicine

Abstract

The compound 7-ethyl-10-hydroxy-camptothecin (SN38) is a broad-spectrum antitumor agent whose applications are greatly limited by its poor solubility. Therefore, irinotecan, the hydrophilic derived prodrug of SN38, has been developed as the commercial formulation Campto® for colorectal cancer. However, only 1% to 0.1% of irinotecan is converted to active SN38 in vivo, thus leading to unsatisfactory antitumor activity in clinical settings. Herein, we report a smart stimuli-responsive SN38 prodrug nanoassembly for efficient cancer therapy. First, SN38 was conjugated with an endogenous lipid, cholesterol (CST), via a redox dual-responsive disulfide bond (namely SN38-SS-CST). The prodrug self-assembled into uniform prodrug nanoassemblies with good colloidal stability and ultrahigh drug loading. SN38-SS-CST NPs released sufficient SN38 in the redox environments of tumor cells but remained intact in normal tissues. Finally, SN38-SS-CST NPs potently inhibited the growth of colon cancer without causing systemic toxicity, thus indicating their promise as a translational chemotherapeutic nanomedicine.

Self-amplifying ROS-sensitive SN38 Dimeric Prodrug nanoparticles for Combined Chemotherapy and Ferroptosis in Cancer Treatment

“…To compare the anti-tumor effects of ferroptosis, we prepared two prodrug nanoparticles containing SN38-CA: SN38-CA NPs and SN38-CA@FC NPs. Nanoparticles were fabricated based on a one-step nanoprecipitation method [22], only an amount of Poloxamer F127 (20%, w/w) was used to increase the stability of the nanoparticles [23].…”

Dual-targeted nanoparticulate drug delivery systems for enhancing triple-negative breast cancer treatment

“…The advent of nanoparticulate drug delivery systems (Nano-DDSs) has opened new avenues in tumor-targeting drug delivery, particularly for combination therapies [17,19]. These systems can encapsulate antitumor agents inside the nanocarriers, extending their systemic circulation time and capitalizing on the enhanced permeability and retention (EPR) effect to passively target tumor tissues, thereby mitigating off-target toxicities [20][21][22]. Crucially, Nano-DDSs can ensure co-delivery of different drugs to tumor cells in optimal ratios, maximizing the synergistic effects [23,24].…”

Probing the Impact of Surface Functionalization Module on the Performance of Mitoxantrone Prodrug Nanoassemblies: Improving the Effectiveness and Safety

“…Prodrug nanoassemblies have developed as promising drug delivery systems due to facile preparation methods, high drug loading, and negligible carrier-related toxicity compared with traditional nanoassemblies. − Furthermore, through the rational design of the chemical structure of the prodrug, the prodrug nanoassemblies can be specifically released at the tumor site while remaining inert in normal tissues, thereby performing high antitumor efficiency with low toxicity. − The prodrug nanoassemblies are generally composed of the following modules: drug modules, modification modules, response modules, and surface functionalization modules. The drug module is mainly cytotoxic drugs that exert pharmacodynamic functions like MTO. − The modification module is nonpharmacological molecules that conjugate with the drug module to form self-assembling prodrugs. , For example, branched chain fatty alcohols can improve the assembly stability of prodrugs by introducing structural defects . The response module is a linker between the drug and the modification modules that enables the smart release of the drug. − Disulfide bond is a common response module that can respond to the tumor redox environment .…”

“…24−26 The modification module is nonpharmacological molecules that conjugate with the drug module to form self-assembling prodrugs. 27,28 For example, branched chain fatty alcohols can improve the assembly stability of prodrugs by introducing structural defects. 29 The response module is a linker between the drug and the modification modules that enables the smart release of the drug.…”