Nanoparticle Albumin-Bound Paclitaxel Targets Pulmonary Neutrophils

Abraxane, a nanoparticle albumin-bound paclitaxel, is a first-line chemotherapeutic that has been clinically approved. It improves the effectiveness of paclitaxel while minimizing side effects. However, the reasons behind Abraxane's therapeutic effects, particularly in lung cancers and metastasis, remain an active area of research. This study investigates a novel mechanism for Abraxane's effects on lung cancers, focusing on how the albumin component of Abraxane interacts with pulmonary neutrophils.

Using radioisotopes or fluorophores, researchers traced the albumin component of Abraxane to the lungs. The lung-specific targeting of Abraxane was found to be enhanced by inflammation. This effect was further demonstrated in mice lacking the complement protein C3, which showed that the complement pathway drives Abraxane's uptake. Flow cytometry and histology revealed that neutrophils are the primary cells within the lungs that absorb Abraxane.

The study confirms that Abraxane exhibits a pronounced affinity for pulmonary neutrophils, both in mice and human donor lungs. While this lung targeting has been previously reported, this research uncovers previously unknown side effects related to Abraxane's lung tropism. These include pro-thrombotic and pro-inflammatory responses during acute lung inflammation. Crucially, the efficacy of Abraxane against lung metastases is diminished when lung uptake is eliminated through the use of C3 knockout mice.

These findings shed light on the reasons why Abraxane is effective in treating lung cancers and metastasis. The insights gained from this study could be instrumental in improving patient outcomes receiving Abraxane and in the development of future cancer nanomedicines.