Nanozymes with multiple catalytic activities for cancer treatment are summarized, and their performances when combined with various cancer treatments or used alone are compared.

Intravesical photodynamic therapy (PDT) emerges as a promising modality for bladder cancer treatment, yet its efficacy is often curtailed by weak muco-adhesion, poor muco-penetration, low tumor-targeting and intra-tumoral oxygen scarcity. In this work, we introduce a drug delivery system leveraging cerium oxide (CeO2) nanozymes as the core, polyarginine peptides R11 as the tumor-targeting ligands, and indocyanine green (ICG) as the photosensitizers, with the latter two components assembled on the particle surface. Intravesical ICG@R11-CeO2 nanoparticles displayed enhanced mucoadhesive, mucus-penetrating and tumor-targeting properties, and effectively mitigated the hypoxia threat in the tumor microenvironment to improve the PDT sensitivity. Remarkably, the intravesical PDT via ICG@R11-CeO2 nanoparticles achieved complete tumor inhibition in orthotopic bladder cancer models, offering strong evidence on its clinical translational potential.

Background: Liver cancer is one of the most prevalent cancers globally, with approximately 90% of primary liver cancers being hepatocellular carcinomas (HCC). However, current systemic treatment options (whether monotherapy or combination therapy) are limited and offer only modest survival benefits. The effectiveness of a drug is largely determined by its concentration at the target site. Therefore, an effective drug delivery system must enhance drug accumulation at the target site, enable selective drug release there, and facilitate escape from lysosomes. Methods: cRGD-Lipo@Ce6/DOX was prepared by modifying c(RGDyK) onto the surface of drug-loaded liposomes containing Chlorin e6 (Ce6) and doxorubicin (DOX) through an amide reaction. The targeting capability and uptake mechanism of cRGD-Lipo@Ce6/DOX for HCC were analyzed using flow cytometry. To investigate drug release mechanisms and changes in subcellular distribution following ultrasound stimulation, further studies were conducted. The therapeutic efficacy and biosafety of this dual-modality therapy were then evaluated in an HCC subcutaneous tumor-bearing mouse model. Results: The prepared nanocomplex exhibits a surface charge of − 9.91 ± 2.94 mV and an apparent size of 118.07 ± 1.46 nm. Modification of the RGD cyclic peptide on the surface of the drug-carrying liposomes enhanced the targeting and penetration efficiency for HCC. In vitro experiments on drug uptake mechanisms and release demonstrated that reactive oxygen species (ROS) generated by sonodynamic therapy (SDT) promote effective drug release from the carrier into the non-lysosomal region. The combined SDT and chemotherapy treatment achieved a 94% tumor inhibition rate and showed excellent biosafety in HCC subcutaneous tumor-bearing mice. Conclusion: Therefore, the effectiveness of the combination treatment strategy utilizing SDT in conjunction with chemotherapy provides additional treatment options for patients with HCC.

Because of low immunogenicity, ease of modification, and inherent biosafety, peptides have been well recognized as vehicles to deliver therapeutic agents to targeted regions with improved pharmacokinetic characteristics. Enzyme-responsive self-assembled peptides (ERSAPs) show superiority over their naive forms due to their enhanced targeting efficacy and long-retention property. In this review, we have summarized recent advances in the therapeutic application of ERSAPs, mainly focusing on their self-therapeutic properties and potential as vehicles to deliver different drugs.

To evaluate the diagnostic performance of an integrated model using intratumoral habitat imaging and peritumoral CT radiomics for preoperative noninvasive