The limited penetration depth of external excitation light would remarkably impair the therapeutic efficacy of
photodynamic therapy (
PDT) and its clinical utilization. Herein, we engineered bioluminescent bacteria by transforming attenuated Salmonella typhimurium strain ΔppGpp (S.T.ΔppGpp) with
firefly-luciferase-expressing plasmid (Luc-S.T.ΔppGpp) as an internal light source to evenly illuminate whole
tumors. Upon being fixed inside
tumors with in-situ formed
hydrogel, the colonized Luc-S.T.ΔppGpp together with
D-luciferin could continuously generate light to excite
photosensitizer chlorin e6 (Ce6), leading to effective suppression of different types of
tumors including opaque
melanoma and large rabbit
tumors. Such bioluminescence-triggered
PDT presented significant advantages over conventional
PDT excited with an external 660-nm light, which at a much high light energy could only slightly retard the growth of small subcutaneous
tumors. Furthermore, we uncovered that Luc-S.T.ΔppGpp boosted
PDT could also elicit potent antitumor immunity post the treatment to inhibit
tumor metastasis and prevent
tumor challenge. Therefore, this work highlights that such bioluminescent bacteria boosted
PDT is a general and highly effective therapeutic approach toward diverse
cancers with varying light-absorbing capacities and
tumor sizes, promising for potential clinical translation because of their acceptable safety profiles.