Аннотация:Photodynamic therapy (PDT) represents a promising strategy for treating solid tumors,offering precise light-triggered activation of photosensitizers to induce localizedcytotoxic effects. Recent advancements in optical technologies have improved lightdelivery and tissue penetration, yet PDT efficacy remains limited by suboptimal drugdelivery mostly due to the inherent complexity of tumor microenvironments. Toovercome this challenge, we developed a macrophage-mediated delivery platformusing layer-by-layer (LbL) microcapsules loaded with two second-generationphotosensitizers: Photoditazine (PD) and aluminum tetrasulfophthalocyanine chloride(PS), an analogue of Photosens. These photosensitizers demonstrated low dark toxicityand high phototoxicity, which are critical for effective and safe transport ofencapsulated cargo by cells into the tumor, making them ideal candidates for safe andefficient PDT. The encapsulation of these dyes in LbL microcapsules (6.2 ± 0.5 μm)with different shell compositions was optimized. Significant differences were observedbetween macrophage types: RAW 264.7 macrophages primarily retained capsules ontheir surface, whereas primary peritoneal macrophages (PMs) internalized capsuleswithin 3 hours and retained them for up to 6 days without degradation.Polyarginine/dextran sulfate ((PArg/DS)4) capsules containing PD exhibited the highestuptake efficiency and facilitated successful macrophage migration into tumorspheroids. In vivo experiments using a CT-26 colon cancer model highlighted thetherapeutic potential of this platform, though further optimization is needed toovercome the challenges posed by large tumors. This study offers new insights intocell-mediated delivery systems and underscores their potential to advance PDToutcomes beyond current limitations.