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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.

Spinal cord injury (SCI) routinely causes the immediate loss and disruption of neurons followed by complicated secondary injuries, including inflammation, oxidative stress, and dense glial scar formation. Inhibitory factors in the lesion scar and poor intrinsic neural regeneration capacity restrict functional recovery after injury. Minocycline, which has neuroprotective activity, can alleviate secondary injury, but the long-term administration of this drug may cause toxicity. Polysialic acid (PSA) is a large cell-surface carbohydrate that is critical for central nervous system development and is capable of promoting precursor cell migration, axon path finding, and synaptic remodeling; thus, PSA plays a vital role in tissue repair and regeneration. Here, we developed a PSA-based minocycline-loaded nanodrug delivery system (PSM) for the synergistic therapy of spinal cord injury. The prepared PSM exerted marked anti-inflammatory and neuroprotective activities both in vitro and in vivo. The administration of PSM could significantly protect neurons and myelin sheaths from damage, reduce the formation of glial scar, recruit endogenous neural stem cells to the lesion site, and promote the regeneration of neurons and the extension of long axons throughout the glial scar, thereby largely improving the locomotor function of SCI rats and exerting a superior therapeutic effect. The findings might provide a novel strategy for SCI synergistic therapy and the utilization of PSA in other central nervous system diseases.