Photodynamic therapy (PDT) is a clinical treatment for cancer or non-neoplastic diseases, and the photosensitizers (PSs) are crucial for PDT efficiency. The commonly used chemical PSs, generally produce ROS through the type II reaction that highly relies on the local oxygen concentration. However, the hypoxic tumor microenvironment and unavoidable dark toxicity of PSs greatly restrain the wide application of PDT. The genetically encoded PSs, unlike chemical PSs, can be modified using genetic engineering techniques and targeted to unique cellular compartments, even within a single cell. KillerRed, as a dimeric red fluorescent protein, can be activated by visible light or upconversion luminescence to execute the Type I reaction of PDT, which does not need too much oxygen and surely attract the researchers’ focus. In particular, nanotechnology provides new opportunities for various modifications of KillerRed and versatile delivery strategies. This review more comprehensively outlines the applications of KillerRed, highlighting the fascinating features of KillerRed genes and proteins in the photodynamic systems. Furthermore, the advantages and defects of KillerRed are also discussed, either alone or in combination with other therapies. These overviews may facilitate understanding KillerRed progress in PDT and suggest some emerging potentials to circumvent challenges to improve the efficiency and accuracy of PDT.

Due to its noninvasive nature, site-confined irradiation, and high tissue penetrating capabilities, ultrasound (US)-driven sonodynamic treatment (SDT) has been proven to have broad application possibilities in neoplastic and non-neoplastic diseases. However, the inefficient buildup of sonosensitizers in the tumor site remarkably impairs SDT efficiency. The present work proposes a deep-penetrating sonochemistry nanoplatform (Pp18-lipos@SRA737&DOX, PSDL) comprising Pp18 liposomes (Pp18-lipos, Plipo), SRA737 (a CHK1 inhibitor), and doxorubicin (DOX) for the controlled formation of reactive oxygen species (ROS) and release of DOX and SRA737 upon US activation, therefore increasing chemotherapeutic effectiveness and boosting SDT efficacy. Therein, the antitumor activities of DOX have been attributed to its intercalation into the nucleus DNA and induction of cell apoptosis. CHK1 evolved to respond to DNA damage and repair the damage via cell cycle progression. SRA737 is a potent and orally bioavailable clinical drug candidate for inhibiting CHK1, demonstrating adjuvant anticancer effect in vitro and in vivo. It was interesting to find that SRA737 carried into Plipo@DOX could significantly alleviate G2/M cell cycle arrest and aggravate DNA double-strand injuries, resulting in significant cell death. The developed US-switchable nanosystem provides a promising strategy for augmenting sono-chemotherapy against breast cancer controllably and precisely.

Cantharidin (CTD), a potent anticancer terpenoid, is clinically limited by its hepatotoxicity and nephrotoxicity, while its impact on the hematopoietic system-particularly on red blood cells (RBCs), remains poorly understood. This study aimed to explore CTD-induced structural and functional changes in RBCs. A series of assays were conducted, including assessments of hemolysis rate, morphological changes, programmed cell death, intracellular reactive oxygen species (ROS), lactate dehydrogenase (LDH) activity, as well as untargeted metabolomics (LC–MS) and proteomics (LC–MS/MS) analyses. Results showed that high-dose CTD (0.8 mM) caused obvious RBCs morphological abnormalities, reduced adhesion and increased intracellular ROS, leading to RBC rupture, LDH release, and ultimately triggering programmed cell death. Multi-omics profiling identified 377 differential metabolites (enriched in ABC transporters and purine metabolism) and 45 differential proteins associated with Hippo and PI3K-Akt pathways. Among these, the PI3K-Akt pathway emerged as the core mechanism underlying CTD-induced RBCs injury. Collectively, this study has accumulated data on CTD-induced morphological and functional disruptions in RBCs, providing some insights for the subsequent evaluation of toxic drugs in the hematopoietic system.