Recent strides in macromolecular targeted photodynamic therapy for cancer

Abstract

The recent approval of Akalux® for antibody-targeted photodynamic therapy (PDT) in Japan (also known as photoimmunotherapy), and the recent approval of Cytalux® for folate-specific image guided surgery by the FDA have motivated the continued development of macromolecular targeted PDT for cancer management. This review spotlights some of the most recent advances in macromolecular targeted PDT since 2021, exploring the latest advances in protein engineering, adaptive macromolecular constructs and nanotechnology, adoption of immune checkpoint inhibitors, and targeting using biomimetic membranes. These strategies summarized here attempt to expand the functionality, benefit, and success of macromolecular targeting for PDT to advance the technology beyond what has already entered into the clinical realm.

Figure 1.

Graphical overview highlighting 5 main molecular targeted PDT modalities that are spotlighted in this review: full-length antibodies, engineered proteins, natural ligands, immune checkpoint inhibitors, and biomimetic membranes. (Created using an academic license of Biorender (biorender.com)).

Figure 2.

Graphic highlighting an immune checkpoint targeting photoactivable liposome system utilizing an anti-PD-L1 antibody for active targeting of pancreatic ductal adenocarcinoma (PDAC). Image reproduced from Bhandari et al.

Figure 3.

Basic outline and overview of biomimetic membranes from active and passive targeting, biological roles, and phototherapy applications. Image reproduced from Chen et al.