Drug Delivery and Translational Research - Featured Article: July 2023
Read the featured article from the July 2023 issue! (this opens in a new tab)
Nanoparticle per-treatment for enhancing the survival and activation of pulmonary macrophage transplant
https://link.springer.com/article/10.1007/s13346-023-01319-6 (this opens in a new tab)
Summary:
Despite recent clinical successes of the chimeric antigen receptor T cell therapy in treating liquid cancers, numerous challenges hamper its broader translation. Macrophage has been proposed as an alternative given its abilities in promoting tumor infiltration, acquiring diverse antigens, and continuously stimulating adaptive responses. However, poor survival of transplanted macrophages and transient retention of anti-tumor phenotype have been major obstacles. Leveraging on recent discoveries of nanoparticle strategies addressing these limitations, we herein report enhanced survival and phenotypic retention of macrophage transplants in murine lungs by pre-treatment with nanoparticles of varying degradation rates. Poly(ethylene glycol) diacrylate nanoparticles prolonged survival of transplanted macrophages over untreated cells, where nanoparticles increased the retention of transplanted cell counts by over 50%. Furthermore, pre-treated macrophages more efficiently retained the pro-inflammatory-like polarization state compared to macrophages pre-treated with a classical pro-inflammatory stimulus, interferon-gamma, where CD86 costimulatory molecule expression was over 150% greater in pre-treated macrophage transplants compared to untreated counterparts. These findings provide an avenue for a major improvement in the lifespan and efficacy of macrophage-based therapies and thus their broader therapeutic implementation.