Adapting and Remolding: Orchestrating Tumor Microenvironment Normalization with Photodynamic Therapy by Size Transformable Nanoframeworks.

Abstract

Abnormal tumor microenvironment (TME) facilitates tumor proliferation and metastasis and establishes physiological barriers for effective transport of therapeutics inside the tumor, posing great challenges for cancer treatment. We designed a core-satellite size transformable nanoframework (denoted as T-PFRT) that can synchronously adapt to and remold TME for augmenting photodynamic therapy to inhibit tumor growth and prevent tumor metastasis. Upon matrix metalloproteinase 2 (MMP2)-responsive dissociation of the nanoframework in TME, the core structure loaded with TGFβ signaling pathway inhibitor and oxygen-carrying hemoglobin aims to stroma remodeling and hypoxia relief, allowing photosensitizer-encapsulated satellite particles to penetrate to deep-seated tumor for oxygen-fueled photodynamic therapy. T-PFRT could overcome the stroma and hypoxia barriers for delivering therapeutics and gain excellent therapeutic outcomes in the treatment of primary and metastatic tumors.

• Authors: Tingxizi Liang, Benhua Zhang, Zejing Xing, Yuxiang Dong, Hongmei Xu, Xueqin Chen, Liping Jiang, Jun-Jie Zhu, Qianhao Min
• Journal: Angewandte Chemie (International ed. in English) (Angew Chem Int Ed Engl) Vol. 60 Issue 20 Pg. 11464-11473 (05 10 2021) ISSN: 1521-3773 [Electronic] Germany
• PMID: 33751758 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Wiley-VCH GmbH.

Chemical References

• Antineoplastic Agents
• Photosensitizing Agents
• Matrix Metalloproteinase 2

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Proliferation (drug effects)
• Drug Delivery Systems
• Drug Screening Assays, Antitumor
• Humans
• Hypoxia (drug therapy)
• Matrix Metalloproteinase 2 (metabolism)
• Molecular Structure
• Nanoparticles (chemistry)
• Particle Size
• Photochemotherapy
• Photosensitizing Agents (chemical synthesis, chemistry, pharmacology)
• Stromal Cells (drug effects)
• Tumor Microenvironment (drug effects)