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Here we demonstrate theranostic immune checkpoint inhibitor nanocomposites (ICI NC) having an improved tumor targeting ability in pulmonary metastatic colon cancer model. Atezolizumab, a PD-L1 antibody, was conjugated with methoxy poly(ethylene glycol) (MePEG) and chlorin e6 (Ce6) via cathepsin-B-sensitive peptide as a linkage (named as ICI nanocomposites, ICI NC). This ICI NC is delivered to tumor sites enriched with tumor-specific enzymes such as cathepsin B, whereas undesired ICI exposure to normal tissue is avoided. When ICI NC were incubated with cathepsin B, Ce6 was released from ICI NC with increased fluorescence intensity in cathepsin B dose-dependent manner, which was by degradation of the peptide and then liberated Ce6 was activated in the aqueous solution. In animal pulmonary metastasis model using CT26 cells, ICI NC showed superior tumor targetability, i.e., fluorescence intensity was significantly strong in the mouse lung having metastatic tumor. On the contrary, cathepsin-B-deficient carriers such as atezolizumab-Ce6 conjugates or atezolizumab-Ce6/MePEG conjugates showed strong fluorescence intensity in the liver as well as lung. Our proposed ICI NC may be used for theranostic cancer therapy with superior tumor specificity of releasing ICI and Ce6 into tumor microenvironment, thereby showing an efficient inhibitory effect on pulmonary metastasis of CT26 cells.

Chlorin e6-Conjugated and PEGylated Immune Checkpoint Inhibitor Nanocomposites for Pulmonary Metastatic Colorectal Cancer