Photodynamic therapy (PDT) is an auspicious therapy approach for the treatment of cancer. Despite its numerous benefits, the drug delivery of the used photosensitizer (PS) to target locations inside the human body remains a main therapy challenge, since the standard intravenous PS injection often causes systemic side-effects. To circumvent this therapy drawback, the oral application represents a promising administration alternative. Especially for the treatment of intestinal cancer it offers the possibility of a local treatment with a reduced likelihood for adverse drug reactions. To establish a suitable drug delivery system for intestinal PDT, we developed nanoparticles (NP) of the biodegradable and biocompatible polymer poly(lactic-co-glycolic) acid (PLGA), loaded with the model PS 5,10,15,20-tetrakis(m-hydroxyphenyl)porphyrin (mTHPP). By functionalizing the particle surface with either poly(ethylene glycol) (PEG) or chitosan (CS), mucus-penetrating or mucoadhesive properties were obtained. These particle characteristics are important to enable an overcoming of the intestinal mucus barrier and thus lead to a PS accumulation close to and in the target cells. In permeation studies with a biosimilar mucus and in cell culture experiments with mucus-covered Caco-2 cells, PEG-modified NP were identified as a superior drug vehicle for an intestinal PDT, compared to surface unmodified or mucoadhesive NP.