Although photodynamic therapy (PDT) has been extensively studied as an established modality of cancer treatment, it still suffers from a few clinical limitations, such as skin phototoxicity and tumor hypoxia. To circumvent these hurdles, hollow silica mesoporous nanoparticles (HMSNs) loaded with photosensitizers were employed as the nanoplatform to construct multifunctional nanoparticles (NPs). Specifically, an ultra-uniform polydopamine (PDA) shell was highly controlled grown around HMSNs by photogenerated outwards-diffused O-1(2), followed by conjugation of folic acid-poly(ethylene glycol) and chelation of Fe2+ ions. Thanks to the optimal thickness of light-absorbing PDA shell, the multifunctional NPs exhibited not only negligible skin phototoxicity but also efficient O-1(2) generation and photothermal (PT)-enhanced (OH)-O-center dot generation upon respective photoirradiation. Anti-tumor therapy was then performed on both 4 T1 tumor cells and tumor-bearing mice by the combination of 638 nm PDT and 808 nm PT enhanced chemodynamic therapy (CDT). As a result, high therapeutic efficacy was achieved compared to single-modality therapy, with a cell inhibitory rate of 86% and tumor growth inhibition of 70.4% respectively. More interestingly, tumor metastasis was effectively inhibited by the synergetic treatment. These results convincingly demonstrate that our multifunctional NPs are very promising skin-safe PDT agents combined with CDT for efficient tumor therapy. (c) 2022 Elsevier Inc. All rights reserved.