Tetrasulfide bond boosts the anti-tumor efficacy of dimeric prodrug nanoassemblies

Carbon-Spaced Tandem-Disulfide Bond Bridge Design Addresses Limitations of Homodimer Prodrug Nanoassemblies: Enhancing Both Stability and Activatability

“…12,13 Despite these advantages, RHPNs are currently only in the preclinical research stage, with their antitumor efficacy limited by the challenges of simultaneously enhancing assembly ability and drug release rate. 14,15 Therefore, constructing RHPNs with a suitable chemical linkage to simultaneously enhance the assembly ability and drug release rate is critical for ensuring stability in systemic circulation and antitumor response in tumors.…”

“…Redox-responsive homodimer prodrugs (HPs) consist of two identical drug molecules bridged by a redox-responsive chemical linkage, which can spontaneously aggregate into nanoassemblies in aqueous medium without the need for adjunct carriers. − Compared with carrier-dependent drug delivery systems such as liposomes and micelles, redox-responsive homodimer prodrug nanoassemblies (RHPNs) integrate the advantages of prodrugs and nanotechnology with ultrahigh drug loading efficiency (over 60%) and avoid carrier-related toxicity. − In addition, the redox-responsive chemical linkage can be triggered by redox substances in the tumor-specific microenvironment, enabling selective drug release. ,, Recently, RHPNs have caught significant attention for their great potential to enhance the effectiveness and safety of chemotherapeutic agents. , Despite these advantages, RHPNs are currently only in the preclinical research stage, with their antitumor efficacy limited by the challenges of simultaneously enhancing assembly ability and drug release rate. , Therefore, constructing RHPNs with a suitable chemical linkage to simultaneously enhance the assembly ability and drug release rate is critical for ensuring stability in systemic circulation and antitumor response in tumors.…”