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Cancer‐associated fibroblasts (CAFs) are present in many types of tumors and play a pivotal role in tumor progression and immunosuppression. Fibroblast‐activation protein (FAP), which is overexpressed on CAFs, has been indicated as a universal tumor target. However, FAP expression is not restricted to tumors, and systemic treatment against FAP often causes severe side effects. To solve this problem, a photodynamic therapy (PDT) approach is developed based on ZnF₁₆Pc‐loaded and FAP‐specific single chain variable fragment (scFv)‐conjugated apoferritin nanoparticles, or αFAP‐Z@FRT. αFAP‐Z@FRT PDT efficiently eradicates CAFs in tumors without inducing systemic toxicity. When tested in murine 4T1 models, the treatment elicits anti‐cancer immunity, causing suppression of both primary and distant tumors, that is, the abscopal effect. Treatment efficacy is enhanced when αFAP‐Z@FRT PDT is used in combination with anti‐PD1 antibodies. Interestingly, it is found that the PDT treatment not only elicits a cellular immunity against cancer cells, but also stimulates an anti‐CAFs immunity. This is supported by an adoptive cell transfer study, where T cells taken from 4T1‐tumor‐bearing animals treated with αFAP PDT retard the growth of A549 tumors established on nude mice. Overall, this approach is unique for permitting site‐specific eradication of CAFs and inducing a broad spectrum anti‐cancer immunity.

Macrophages hold great potential in cancer drug delivery because they can sense chemotactic cues and home to tumors with high efficiency. However, it remains a challenge to load large amounts of therapeutics into macrophages without compromising cell functions. This study reports a silica‐based drug nanocapsule approach to solve this issue. The nanocapsule consists of a drug–silica complex filling and a solid silica sheath, and it is designed to minimally release drug molecules in the early hours of cell entry. While taken up by macrophages at high rates, the nanocapsules minimally affect cell migration in the first 6–12 h, buying time for macrophages to home to tumors and release drugs in situ. In particular, it is shown that doxorubicin (Dox) as a representative drug can be loaded into macrophages up to 16.6 pg per cell using this approach. When tested in a U87MG xenograft model, intravenously (i.v.) injected Dox‐laden macrophages show comparable tumor accumulation as untreated macrophages. Therapy leads to efficient tumor growth suppression, while causing little systematic toxicity. This study suggests a new cell platform for selective drug delivery, which can be readily extended to the treatment of other types of diseases.