Intricate mesoporous biosilica has many biomedical applications as a nanocarrier. However, its potential use in photodynamic therapy (PDT) has received little attention. This work reports the first fabrication of bio-engineered materials by covalently conjugating C-phycocyanin (C-PC), a natural photosensitizer, to biosilica for the PDT of tumor-associated macrophages. The resulting hybrid material showed outstanding photodynamic activity under 620 nm laser irradiation. Furthermore, it enhanced the relatively weak photodynamic effect of C-PC. This study also explored methods of biofunctionalizing biosilica for cancer phototherapy, a new pharmacological application of non-toxic C-PC. (C) 2020 Elsevier Inc. All rights reserved.