The blood-brain barrier (BBB) hampers the delivery of drugs into the brain. In an effort to bypass this barrier, novel drug engineering strategies have been developed wherein vectors that interact with specific receptors present in the BBB are coupled to vehicles used for drug loading. This approach allows for efficient drug targeting to the brain while minimizing non-specific or systemic side effects and avoiding the potential for multidrug efflux. The transferrin family protein lactoferrin (Lf) is an iron-binding glycoprotein that is cationic in nature, and which has been shown to mediate immunological activity and to be capable of decreasing inflammation and preventing microbial infections. The receptor for Lf (LfR) is present at the BBB, thereby serving to transport Lf across this biological barrier in vivo. We have previously found that Lf can be effectively used to target compounds to the brain. In the present study, we conjugated Lf to black phosphorus nanosheets (BPNSs), thereby generating a novel system for delivering drugs to the brain (Lf-BPNSs). BPNSs exhibit ideal photothermal activity in response to near infrared (NIR) irradiation, with such activity being associated with increased permeability of the BBB. We loaded these Lf-BPNs with paeoniflorin (PAE), which is a compound that has shown promise against symptoms of Parkinson’s disease (PD), yielding Lf-BPNSs-PAE. The ability of Lf-BPNSs-PAE to mediate neuroprotection following its intravenous administration was then assessed in PD model mice bearing lesions generated using examined in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Our results suggest that Lf-BPNSs offer promise as a means of targeting drugs to the brain, serving as a potential platform for drug delivery in the context of PD and other diseases of the central nervous system.