Emerging evidence indicates that the activation of ferroptosis by glutathione peroxidase 4 (GPX4) inhibitors may be a prominent therapeutic strategy for tumor suppression. However, the wide application of GPX4 inhibitors in tumor therapy is hampered due to poor tumor delivery efficacy and the nonspecific activation of ferroptosis. Taking advantage of in vivo self-assembly, we develop a peptide-ferriporphyrin conjugate with tumor microenvironment specific activation to improve tumor penetration, endocytosis and GPX4 inhibition, ultimately enhancing its anticancer activity via ferroptosis. Briefly, a GPX4 inhibitory peptide is conjugated with an assembled peptide linker decorated with a pH-sensitive moiety and ferriporphyrin to produce the peptide-ferriporphyrin conjugate (Gi-F-CAA). Under the acidic microenvironment of the tumor, the Gi-F-CAA self-assembles into large nanoparticles (Gi-F) due to enhanced hydrophobic interaction after hydrolysis of CAA, improving tumor endocytosis efficiency. Importantly, Gi-F exhibits substantial inhibition of GPX4 activity by assembly enhanced binding (AEB) effect, augmenting the oxidative stress of ferriporphyrin-based Fenton reaction, ultimately enabling antitumor properties in multiple tumor models. Our findings suggest that this peptide-ferriporphyrin conjugate design with AEB effect can improve the therapeutic effect via induction of ferroptosis, providing an alternative strategy for overcoming chemoresistance.

A biomimetic platelet based on assembling peptides initiates artificial coagulation for tumor therapy.

As a promising delivery nanosystem for drug controlled-release, nanocarriers (NCs) have been investigated widely. Although various studies have concentrated on the preparation and characterization of nanoparticles (NPs), clinical applications are rarely reported, due to the unclear distribution, absorption, metabolism, toxicology processes and drug release mechanism. The clinical application of NCs is therefore still a long way off. This review describes the effects of the properties of NCs (including size, shape, surface properties, porosity, elasticity and so on) on pharmacological and toxicological behaviours in vivo and medical applications. Moreover, this study is intended to help the readers understand the behaviours and mechanisms of NCs and positively face the challenges caused by the variety of complicated and limited processes of NCs in vivo. Importantly, this article provides some strategies for the clinical application of NCs and may provide ideas to enhance the therapeutic efficacy of NCs without increasing the toxicology, by introducing tracing technology, which can be more suitable in contributing to the development of safety and efficacy of NCs and the growth of nanotechnology.