Tumor Therapy Strategies Based on Microenvironment‐Specific Responsive Nanomaterials

Abstract

The tumor microenvironment (TME) is a complex and variable region characterized by hypoxia, low pH, high redox status, overexpression of enzymes, and high‐adenosine triphosphate concentrations. In recent years, with the continuous in‐depth study of nanomaterials, more and more TME‐specific response nanomaterials are used for tumor treatment. However, the complexity of the TME causes different types of responses with various strategies and mechanisms of action. Aiming to systematically demonstrate the recent advances in research on TME‐responsive nanomaterials, this work summarizes the characteristics of TME and outlines the strategies of different TME responses. Representative reaction types are illustrated and their merits and demerits are analyzed. Finally, forward‐looking views on TME‐response strategies for nanomaterials are presented. It is envisaged that such emerging strategies for the treatment of cancer are expected to exhibit dramatic trans‐clinical capabilities, demonstrating the extensive potential for the diagnosis and therapy of cancer.

Tumor microenvironment-responsive degradable silica nanoparticles: design principles and precision theranostic applications

“…), and varying expression of cell types and surface receptors. [9][10][11][12][13]97 TMEresponsive nanotherapeutics are diagnostic and therapeutic agents specifically engineered to target the TME in cancer and are capable of responding to specific conditions or signals within the TME, thereby achieving precise diagnosis and treatment. 13,98 These nanotherapeutics hold significant promise in the realms of cancer theranostics, as they have the potential to enhance treatment effectiveness, minimize side effects, and propel the advancement of personalized medicine.…”

“…[9][10][11][12][13]97 TMEresponsive nanotherapeutics are diagnostic and therapeutic agents specifically engineered to target the TME in cancer and are capable of responding to specific conditions or signals within the TME, thereby achieving precise diagnosis and treatment. 13,98 These nanotherapeutics hold significant promise in the realms of cancer theranostics, as they have the potential to enhance treatment effectiveness, minimize side effects, and propel the advancement of personalized medicine. In this section, we systematically present the latest advancements in the research of TME-responsive degradable silica nanoparticles, elucidating representative types of biological triggers, including pH, redox, hypoxia, and enzymes.…”

“…It exhibits distinctive features, such as dynamic hypoxia, high concentrations of redox components, elevated intracellular adenosine triphosphate (ATP) and lactate levels, and extracellular acidosis. [6][7][8][9][10][11][12][13] Additionally, certain types of tumors possess specific microenvironments. Vascular tumors are characterized by vascular leakage, chaotic branching of blood vessels, uneven blood flow distribution, and high stromal fluid pressure, while stromal tumors present prominent features of abnormal tumor-associated fibroblasts and a dense extracellular matrix.…”

Magnetically Stimulated Integrin Binding Alters Cell Polarity and Affects Epithelial–Mesenchymal Plasticity in Metastatic Cancer Cells

“…Despite advancements in cancer therapies, challenges persist in enhancing the efficacy and minimizing side effects in tumor treatment and drug development. A promising avenue of research involves utilizing cellular microenvironment (CME)-reactive nanomaterials, such as iron oxide magnetic nanoparticles (MNPs), to create complex and dynamic artificial microenvironments . These MNPs are tailored to elicit specific cellular responses by applying controlled physical stimuli via an external magnetic field, which alters the cell polarization and behavior.…”

Enzyme-Induced Shape-Shifting Peptide Nanocarrier Coloaded with Paclitaxel and Dipyridamole Inhibits Platelet Function and Tumor Metastasis

“…The TME is a complex and variable region characterized by hypoxia, low pH, and the overexpression of enzymes. Some features of the TME provide conditions suitable for precise tumor-targeting therapies. − A high level of alkaline phosphatase (ALP) is an important marker of metastasis and poor healing in breast cancer . Utilizing ALP to induce structural changes in peptide nanocarriers offers a promising approach to enhancing the duration of chemotherapeutic agent retention at the tumor location …”