Herein, a novel phototheranostic nanocomplex that is self-assembled from bovine serum albumin (BSA) and indocyanine green (ICG) is developed for enhanced near-infrared (NIR) fluorescence imaging, which benefits the guidance on in vivo cancer photothermal therapy (PTT). The study confirms that the binding of ICG with the bind sits on the albumin will result in improved hydrolytic stability and high photoluminescence quantum yield (PLQY). The ICG loading ratio in the nanocomplex is optimized and confirms the loading ratio of 0.5% ICG to be the optimal content. The optimized ICG-BSA nanocomplex (ICG-BSA NC) possesses a higher PLQY of 16.8% than that of free ICG (2.7%). The high PLQY and efficient passive targeting ability of ICG-BSA NC help improve its in vivo tumor accumulation and NIR fluorescence imaging significantly. Under laser irradiation, efficient PTT with obvious tumor growth suppression on a triple negative breast tumor model can be observed in the ICG-BSA NC treated group.

Sonodynamic therapy (SDT), which uses ultrasound to trigger a sonosensitizer to generate reactive oxygen species (ROS), is a promising form of cancer therapy with outstanding tissue penetration depth. However, the sonosensitizer may inevitably spread to surrounding healthy tissue beyond the tumor, resulting in undesired side effects under an ultrasound stimulus. Herein, as glutathione (GSH) is overexpressed in the tumor microenvironment, a GSH‐activatable sonosensitizer prodrug is designed by attaching a quencher to tetraphydroxy porphyrin for tumor therapy. The prodrug exhibits poor fluorescence and low ROS generation capacity under ultrasound irradiation, but it also showed that it can be activated by GSH to simultaneously switch on fluorescence emission and ROS generation capability at the tumor site. Compared with the non‐quenched sonosensitizer, the designed prodrug exhibits significantly higher tumor/healthy organ fluorescence ratios, due to the specific fluorescence and ROS activation by overexpressed GSH in the tumor. Finally, the prodrug exhibits efficient tumor growth inhibition under ultrasound irradiation, further demonstrating its promise as a GSH‐activated sonosensitizer prodrug for highly effective cancer treatment.

No abstract

The RAS-RAF-MEK-ERK signaling pathway (MAPK signaling) is hyperactivated in more than 30% of human cancers. The abnormal activation of this pathway is mainly due to the gain-offunction mutations in RAS or RAF genes. Furthermore, the crucial roles of mitogen-activated protein kinase kinase (MEK) in tumorigenesis, cell proliferation and apoptosis inhibition, make MEK inhibitors (MEKi) attractive candidates for the targeted therapy of MAPK pathway-related cancer. Several highly selective and potent non-ATP-competitive allosteric MEKi have been developed and have led to substantial improvements in clinical outcomes. However, the drug efficacies and response rates are limited due to complex pathway cross-talk and pessimistic drug solubility. Nanosized modifications have made great contributions to improving drug efficacies over the past decades. In this review, the important biological status of MEK kinase in the MAPK pathway is illuminated primarily to highlight the irreplaceable position and clinical status of MEKi. In addition, nanomodification strategies to enhance drug efficacy are briefly summarized, followed by the application advances of nanotechnology in the field of MEKi-related cancer theranostics. Finally, the obstacles impeding the development of nanosized MEKi are considered, and promising prospects are suggested. This informative report lays the groundwork for the clinical development of MEKi and outlines a rational frontline-treatment approach for personalized cancer treatment.

Various nanocarriers have been explored to deliver drugs for combination therapy. However, most nanocarriers are composed of inert materials without contribution for improving the cancer therapeutic effect. Herein, a hydrophobic photosensitizer is conjugated to poly (ethylene glycol) to form an amphiphilic polymer, which further self-assembles into nanomicelle. The generated nanomicelle can act as a nanocarrier to encapsulate a cytotoxic molecule, IR-775, for combination therapy. The yielded nanodrug is totally composed of pharmacologically active ingredients to avoid any possible toxicity resulted from carrier materials. The nanodrug performs enhanced therapeutic effect compared with any monotherapy and exhibits negligible hemolysis, indicating good biocompatibility for further in vivo applications.