TY - JOUR
T1 - Ion-dependent slow protein release from in vivo disintegrating micro-granules
AU - Álamo, Patricia
AU - Parladé, Eloi
AU - López-Laguna, Hèctor
AU - Voltà-Durán, Eric
AU - Unzueta, Ugutz
AU - Vazquez, Esther
AU - Mangues, Ramon
AU - Villaverde, Antonio
N1 - Publisher Copyright:
© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021
Y1 - 2021
N2 - Through the controlled addition of divalent cations, polyhistidine-tagged proteins can be clustered in form of chemically pure and mechanically stable micron-scale particles. Under physiological conditions, these materials act as self-disintegrating protein depots for the progressive release of the forming polypeptide, with potential applications in protein drug delivery, diagnosis, or theragnosis. Here we have explored the in vivo disintegration pattern of a set of such depots, upon subcutaneous administration in mice. These microparticles were fabricated with cationic forms of either Zn, Ca, Mg, or Mn, which abound in the mammalian body. By using a CXCR4-targeted fluorescent protein as a reporter building block we categorized those cations regarding their ability to persist in the administration site and to sustain a slow release of functional protein. Ca2+ and specially Zn2+ have been observed as particularly good promoters of time-prolonged protein leakage. The released polypeptides result is available for selective molecular interactions, such as specific fluorescent labeling of tumor tissues, in which the protein reaches nearly steady levels.
AB - Through the controlled addition of divalent cations, polyhistidine-tagged proteins can be clustered in form of chemically pure and mechanically stable micron-scale particles. Under physiological conditions, these materials act as self-disintegrating protein depots for the progressive release of the forming polypeptide, with potential applications in protein drug delivery, diagnosis, or theragnosis. Here we have explored the in vivo disintegration pattern of a set of such depots, upon subcutaneous administration in mice. These microparticles were fabricated with cationic forms of either Zn, Ca, Mg, or Mn, which abound in the mammalian body. By using a CXCR4-targeted fluorescent protein as a reporter building block we categorized those cations regarding their ability to persist in the administration site and to sustain a slow release of functional protein. Ca2+ and specially Zn2+ have been observed as particularly good promoters of time-prolonged protein leakage. The released polypeptides result is available for selective molecular interactions, such as specific fluorescent labeling of tumor tissues, in which the protein reaches nearly steady levels.
KW - Protein materials
KW - microparticles
KW - protein depots
KW - self-disintegrating materials
KW - tumor targeting
UR - http://www.scopus.com/inward/record.url?scp=85118917792&partnerID=8YFLogxK
U2 - 10.1080/10717544.2021.1998249
DO - 10.1080/10717544.2021.1998249
M3 - Article
C2 - 34747685
AN - SCOPUS:85118917792
SN - 1071-7544
VL - 28
SP - 2383
EP - 2391
JO - Drug Delivery
JF - Drug Delivery
IS - 1
ER -