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The lack of effective drug delivery strategies has impaired the therapeutic progress in the treatment of glioblastoma (GBM). Here, the authors engineer synthetic protein nanoparticle based on polymerized human serum albumin equipped with the cell-penetrating peptide iRGD to deliver siRNA against STAT3 and report improved survival in a mouse model of GBM.

Glioblastoma is an aggressive brain tumor with poor prognosis. The brain is protected by the blood–brain barrier, which precludes transport of chemotherapeutics. We developed nanoparticles that achieve delivery of small-interfering RNA against Stat3 after systemic administration. Nanoparticles combined with radiation inhibited tumor progression and elicited anti-glioblastoma immunity in mice.

Unwanted uptake in the liver and limited accumulation in target organs is a major obstacle to targeted drug delivery. Here, the authors report on the hitchhiking of nanocarriers on red blood cells and the targeted upstream delivery to different target organs in mice, pigs and ex vivo human lungs.