Photothermal Nanoheaters-Modified Spores for Safe and Controllable Antitumor Therapy

INTRODUCTION: To present a safer tumor therapy based on bacteria and identify in detail how the activation and infection behavior of spores can be controlled remotely by near-infrared light (NIR-irradiation) based on nanoheaters’ modification. METHODS: Spores bring a better tolerance to surface modification. Transitive gold-nanorods-allied-nanoclusters-modified spores (Spore@NRs/NCs) were constructed by covalent glutaraldehyde crosslink. The photothermal properties of nanoheaters before and after attachment to spores were studied by recording temperature–irradiation time curves. The controlled viability and infection behavior of Spore@NRs/NCs were investigated by NIR-irradiation. RESULTS: In this work, a controllable sterilizing effect to activated vegetative bacteria was obtained obviously. When met with a suitable growth-environment, Spore@NRs/NCs could germinate, activate into vegetative bacteria and continue to reproduce. Without NIR-irradiation, nanoheaters could not affect the activity of both spores and vegetative bacterial cells. However, with NIR-irradiation after incubating in growth medium, nanoheaters on spores could control the spores’ germination and affect the growth curve as well as the viability of the vegetative bacterial cells. For Spore@NRs/NCs (Spore:NCs:NRs=1:1:4, 67.5 μg mL(−1)), a ~98% killing rate of vegetative bacterial cells was obtained with NIR-irradiation (2.8 W cm(−2), 20 min) after 2 h-incubation. In addition, these nanoheaters modified on spores could be taken not only to the vegetative bacteria cells, but also to the first-generation bacteria cells with their excellent photothermal and bactericidal performance, as well as synergetic anticancer effect. NIR-irradiation after 2 h-incubation could also trigger Spore@NRs/NCs (1:1:4, 6 μL) to synergistically reduce the viability of HCT116 cells to 15.63±2.90%. CONCLUSION: By using NIR-irradiation, the “transitive” nanoheaters can remotely control the activity of both bacteria (germinated from spore) and cancer cells. This discovery provides basis and a feasible plan for controllable safer treatment of bacteria therapy, especially anaerobes with spores in hypoxic areas of the malignant solid tumors.