Results
Title

A Polymeric Extracellular Matrix Nanoremodeler for Activatable Cancer Photo‐Immunotherapy.

Authors

Zhang, Chi; Xu, Mengke; Zeng, Ziling; Wei, Xin; He, Shasha; Huang, Jingsheng; Pu, Kanyi

Abstract

Cancer immunotherapy has shown tremendous potential to train the intrinsic immune system against malignancy in the clinic. However, the extracellular matrix (ECM) in tumor microenvironment is a formidable barrier that not only restricts the penetration of therapeutic drugs but also prevents the infiltration of antitumor immune cells. We herein report a semiconducting polymer‐based ECM nanoremodeler (SPNcb) to combine photodynamic antitumor activity with cancer‐specific inhibition of collagen‐crosslinking enzymes (lysyl oxidase (LOX) family) for activatable cancer photo‐immunotherapy. SPNcb is self‐assembled from an amphiphilic semiconducting polymer conjugated with a LOX inhibitor (β‐aminopropionitrile, BAPN) via a cancer biomarker (cathepsin B, CatB)‐cleavable segment. BAPN can be exclusively activated to inhibit LOX activity in the presence of the tumor‐overexpressed CatB, thus blocking collagen crosslinking and decreasing ECM stiffness. Such an ECM nanoremodeler synergizes immunogenic phototherapy and checkpoint blockade immunotherapy to improve the tumor infiltration of cytotoxic T cells, inhibiting tumor growth and metastasis.

Subjects

EXTRACELLULAR matrix; CYTOTOXIC T cells; PROGRAMMED cell death 1 receptors; LYSYL oxidase; CATHEPSIN B; TUMOR growth

Publication

Angewandte Chemie, 2023, Vol 135, Issue 12, p1

ISSN

0044-8249

Publication type

Academic Journal

DOI

10.1002/ange.202217339