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Replacing heme with paclitaxel to prepare drug-loaded globin nanoassembles for CD163 targeting.

Protein-based nanoparticles hold great promises in both preclinical and clinical practices, such as oncology diagnosis and treatment, because of their high biocompatibility and biodegradability. However, the complicated preparation and lack of targeting specific cells or tissues may limit their further uses. To overcome these limitations, we developed a novel replacing method for preparing dual-functional protein nanocarrier, such that one function is capable of encapsulating small molecule into protein, whereas the other function is cable of recognizing CD163 receptor [hemoglobin (Hb) scavenger receptor]. In this study, Hb was chosen as the targeting drug carrier. First, the heme group in the Hb was removed and replaced by paclitaxel (PTX) to form nanoparticles (Gb-NPs-PTX). The resulted Gb-NPs-PTX showed spherical shape and their diameter could be controlled in the range of 120-160 nm by altering the ratio of PTX to Hb. The binding activity of Gb-NPs-PTX to CD163 was confirmed by cell uptake in CD163(+) Chinese hamster ovary cells. Results in vivo also showed a CD163-dependent tissue accumulation of Gb-NPs-PTX in mice. In summary, by using the novel replacing method, PTX could be easily encapsulated into Hb nanoparticles and the targeting effects of Hb could also be kept.