TLR7 Agonist-Loaded Gadolinium Oxide Nanotubes Promote Anti-Tumor Immunity by Activation of Innate and Adaptive...

Improving the delivery of biomolecules to DCs and lymph nodes is critical to increasing their anti-tumor efficacy, reducing their off-target side effects, and improving their safety. In this study, Gd₂O₃ nanotubes with lengths of 70-80 nm, diameters of 20-30 nm, and pore sizes of up to 18 nm were synthesized using a facile one-pot solvothermal method. The Gd₂O₃ nanotubes showed good adsorption capacity of OVA and TLR7a, with a loading efficiency of about 100%. The Gd₂O₃ nanotubes showed pH-sensitive degradation and biomolecule release properties; the release of gadolinium ions, OVA, and TLR7a was slow at pH 7.4 and fast at pH 5. The Gd₂O₃ nanotubes showed 2.6-6.0 times higher payload retention around the injection site, 3.1 times higher cellular uptake, 1.7 times higher IL1β secretion, 1.4 times higher TNFα secretion by BMDCs, and markedly enhanced draining lymph node delivery properties. The combination of OVA, TLR7a, and Gd₂O₃ nanotubes significantly inhibited tumor growth and increased survival rate compared with only OVA-TLR7a, only OVA, and saline. The Gd₂O₃ nanotubes are biocompatible and can also be used as radiation sensitizers.