Subcutaneous administration of an endocrine-mimetic platform allows for prolonged tumor uptake of a tumor targeting protein
Por:
Alamo, P, López-Laguna, H, Favaro, MTP, Gallardo, A, Alba-Castellon, L, Villaverde, A, Mangues, R, Vázquez, E
Publicada:
10 feb 2026
Ahead of Print:
1 ene 2026
Resumen:
Endocrine-like dynamic protein depots can be fabricated in vitro through the coordination of divalent zinc ions (Zn2+) with solvent-exposed histidine residues on functional proteins, leading to their controlled aggregation. The resulting microparticles, under physiological conditions, undergo progressive disintegration due to spontaneous Zn dilution, enabling a time-sustained release of the protein components. These chemically pure proteinbased materials represent promising drug delivery platforms, with demonstrated efficacy in oncology, vaccinology, tissue regeneration, and antibacterial therapies. To enable systemic delivery of the embedded protein, alternative administration routes are potentially suited, but their effectiveness in terms of biodistribution and accumulation in target tissues remains unexplored. Using a CXCR4+ cancer mouse model, we investigated the tumor targeting and permanence of a self-assembling, CXCR4-binding fluorescent protein administered in the form of secretory granules via subcutaneous, intramuscular, or intraperitoneal injection. Our data reveal that subcutaneous administration supports prolonged protein retention at the injection site, its release within the local draining lymphatic vessels, extended circulation time, and significantly higher tumor accumulation 10 days post-injection. Compared to intramuscular and intraperitoneal routes, the subcutaneous pathway presents clear advantages, potentially allowing reduced dosing frequency in protein-based therapies aimed at maintaining steady systemic and target tissue levels.
Filiaciones:
Alamo, P:
Inst Recerca St Pau IR ST PAU, Oncohematol Dis Dept, Barcelona 08041, Spain
Univ Autonoma Barcelona, Nanoligent SL, Edifici Eureka, Bellaterra 08193, Spain
López-Laguna, H:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Bellaterra 08193, Spain
Univ Autonoma Barcelona, CIBER Bioingn Biomat & Nanomed, ISCIII, Barcelona 08193, Spain
Univ Int Catalunya, Fac Med & Hlth Sci, Dept Biomed Sci, Sant Cugat Del Valles, Spain
Favaro, MTP:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Bellaterra 08193, Spain
Univ Autonoma Barcelona, CIBER Bioingn Biomat & Nanomed, ISCIII, Barcelona 08193, Spain
Gallardo, A:
Inst Recerca St Pau IR ST PAU, Oncohematol Dis Dept, Barcelona 08041, Spain
Univ Autonoma Barcelona, CIBER Bioingn Biomat & Nanomed, ISCIII, Barcelona 08193, Spain
Alba-Castellon, L:
Inst Recerca St Pau IR ST PAU, Oncohematol Dis Dept, Barcelona 08041, Spain
Univ Autonoma Barcelona, CIBER Bioingn Biomat & Nanomed, ISCIII, Barcelona 08193, Spain
Villaverde, A:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Bellaterra 08193, Spain
Univ Autonoma Barcelona, CIBER Bioingn Biomat & Nanomed, ISCIII, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Bellaterra 08193, Spain
Mangues, R:
Inst Recerca St Pau IR ST PAU, Oncohematol Dis Dept, Barcelona 08041, Spain
Univ Autonoma Barcelona, CIBER Bioingn Biomat & Nanomed, ISCIII, Barcelona 08193, Spain
Vázquez, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Bellaterra 08193, Spain
Univ Autonoma Barcelona, CIBER Bioingn Biomat & Nanomed, ISCIII, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Bellaterra 08193, Spain
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