Three Strategies in Engineering Nanomedicines for Tumor Microenvironment‐Enabled Phototherapy

Abstract

Canonical phototherapeutics have several limitations, including a lack of tumor selectivity, nondiscriminatory phototoxicity, and tumor hypoxia aggravation. The tumor microenvironment (TME) is characterized by hypoxia, acidic pH, and high levels of H2O2, GSH, and proteases. To overcome the shortcomings of canonical phototherapy and achieve optimal theranostic effects with minimal side effects, unique TME characteristics are employed in the development of phototherapeutic nanomedicines. In this review, the effectiveness of three strategies for developing advanced phototherapeutics based on various TME characteristics is examined. The first strategy involves targeted delivery of phototherapeutics to tumors with the assistance of TME‐induced nanoparticle disassembly or surface modification. The second strategy involves near‐infrared absorption increase‐induced phototherapy activation triggered by TME factors. The third strategy involves enhancing therapeutic efficacy by ameliorating TME. The functionalities, working principles, and significance of the three strategies for various applications are highlighted. Finally, possible challenges and future perspectives for further development are discussed.

Exosome-mediated communication between gastric cancer cells and macrophages: implications for tumor microenvironment

“…These substances can change their physical properties, composition, and the environment in which they live to affect tumor cell migration, while the concentration of ECM also determines the ratio of tumor cell migration from one region to another (72)(73)(74)(75)(76). Additionally, nonmalignant cells in the TME are prominently separated into two primary groups, immune cells and mesenchymal stromal cells, which stimulate and promote uncontrolled cell proliferation to affect all stages of carcinogenesis (77)(78)(79). In the tumor microenvironment, immune cells are made up of both adaptive and intrinsic immune cells (80)(81)(82), and the two categories of lymphocytes, T and B lymphocytes, are essential integrants of adaptive immune cells.…”

A copper-loaded self-assembled nanoparticle for disturbing the tumor redox balance and triple anti-tumor therapy

“…Nevertheless, the complicated tumor microenvironment (TME) poses great challenges for current cancer therapy strategies. 17,18 One of the major factors is the antioxidant defense system, mainly attributed to the overexpressed glutathione (GSH) in tumor cells that can regulate the oxidative stress and bring anticancer drug resistance. 19,20 In particular, GSH, an important antioxidative molecule and one of the biomarkers overexpressed in cancer, has the ability to scavenge ROS and result in the reduction of ROS-related therapeutic efficiency.…”

Mercaptosuccinic Acid-Based Carbon Quantum Dots as Peroxidase-like Nanozymes Inducing Cell Pyroptosis for Tumor-Specific Therapy

“…Nonspecific targeting and low efficiency remain critical issues and major challenges in treating tumors. Tumor microenvironment (TME) is given abundant specific features like a weakly acidic condition (pH 6.4–7.0), hypoxia, inflammation and overproduced hydrogen peroxide (H 2 O 2 , 50–100 μM). − Such specific endogenous metabolic microenvironment phenotypes different from normal tissues (pH 7.4) may be exploited strategically to trigger in situ catalysis of nanozymes for precise tumor-specific treatment. , …”