ArticleJournal of nanobiotechnology2026
Guiding off-target nanomedicine repurposing in spleen for cancer immunotherapy.
Article in Journal of nanobiotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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12 authors.
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Abstract
The inevitable splenic sequestration of nanomedicine represents a major delivery challenge that compromises tumor accumulation and may contribute to off-target burden. Rather than attempting to eliminate this fate, we propose to functionally repurpose it into an immunologically productive process. Distinct from conventional spleen-targeted strategies, we aimed to modulate the biological fate of tumor-targeted nanomedicines by engineering their surface with screening-selected hybrid cell membranes. A tumor cell membrane-to-erythrocyte membrane ratio of 10:1(TRM) was identified as a representative balance point that preserves optimal tumor-associated accumulation while biasing a fraction of off-target nanoparticles (NPs) toward the spleen. Zinc imidazolate framework-8 (ZIF-8) NPs were employed as a model therapeutic core. The resulting hybrid cell membrane-camouflaged nanoplatform (TRM@ZIF-8) exhibited immune-associated effects, where the tumor-associated fraction was linked to inflammasome-related signaling and inflammatory cell death-associated responses, while the spleen-biased fraction was associated with activation of splenic antigen-presenting cells. This behavior is consistent with the collective influence of membrane-associated protein features, including functions related to cluster of differentiation 47(CD47) and Band 3, together with the intrinsic immunostimulatory properties of the ZIF-8 core. Importantly, splenectomy markedly attenuated the therapeutic effect, providing organ-level evidence that spleen involvement is functionally associated with the observed antitumor immune response and tumor growth suppression. This work provides a proof-of-concept framework for guiding off-targeted nanomedicine repurposing in spleen for cancer immunotherapy, rather than regarding it solely as a delivery limitation.
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