Cationic anticancer
peptides, which can induce
tumor cell immunogenic death and further promote systemic
tumor-specific immune responses, have offered a promising
solution to relieve the
tumor immunosuppressive microenvironment. However,
peptide drugs are easily degraded and lack of targeting ability when administered systemically, leading to limitations in their applications. Herein, we report a pH and thermal dual-sensitive bovine
lactoferricin-loaded (one of the most widely studied cationic anticancer
peptides) nanoparticles, which simultaneously exhibited antitumor and immune cell activated effects when applied with microwave
thermotherapy, an auxiliary method of
immunotherapy. The bovine
lactoferricin could be delivered to the
tumor site by nanoparticles, be immediately released from nanoparticles in the acidic environment of lysosomes and the thermal condition caused by microwave radiation, and ultimately induce
tumor apoptosis with the release of damage-associated molecular patterns (DAMPs). It is worth noting that the strategy of bovine
lactoferricin-loaded nanoparticles
intravenous injection combined with local microwave
thermotherapy not only showed excellent efficacy in relieving
tumor growth but also resulted in strong antitumor immunities, which was due to the released bovine
lactoferricin under stimulating conditions, and the pool of
tumor-associated
antigens generated by
tumor destruction. In conclusion, this work presents a strategy for
tumor treatment based on dual-sensitive bovine
lactoferricin-loaded nanoparticles combined with microwave
thermotherapy, which may provide a
solution for cationic anticancer
peptides delivery and improving antitumor immune responses.