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Theranostic dendrimer-based lipid nanoparticles containing PEGylated BODIPY dyes for tumor imaging and systemic mRNA delivery in vivo.


ABSTRACT: mRNA-based therapeutics have emerged as a promising approach to treat cancer. However, creation of theranostic strategies to both deliver mRNA and simultaneously detect cancer is an important unmet goal. Here, we report the development of theranostic dendrimer-based lipid nanoparticle (DLNP) system containing PEGylated BODIPY dyes (PBD) for mRNA delivery and near-infrared (NIR) imaging in vitro and in vivo. DLNPs formulated with a pH-responsive PBD-lipid produced 5- to 35-fold more functional protein than control DLNPs formulated with traditional PEG-lipid in vitro and enabled higher mRNA delivery potency in vivo at a low dose of 0.1 mg kg-1 when formulated with a PBD-lipid containing a BODIPY core, indole linker, and PEG length between 1000 and 5000 g/mol. Moreover, we found the intensity of mRNA expression in the liver correlated with the pKa of DLNPs, indicating that DLNPs with a pKa close to 6.3 could generally produce more protein in livers. Notably, 4A3-SC8&PEG2k5d formulated DLNPs successfully mediated mRNA expression in tumors and simultaneously illuminated tumors via pH-responsive NIR imaging. The described theranostic lipid nanoparticles that combine mRNA delivery and NIR imaging hold promise as an applicable future approach to simultaneously detect and treat cancer.

SUBMITTER: Xiong H 

PROVIDER: S-EPMC8152631 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Theranostic dendrimer-based lipid nanoparticles containing PEGylated BODIPY dyes for tumor imaging and systemic mRNA delivery in vivo.

Xiong Hu H   Liu Shuai S   Wei Tuo T   Cheng Qiang Q   Siegwart Daniel J DJ  

Journal of controlled release : official journal of the Controlled Release Society 20200703


mRNA-based therapeutics have emerged as a promising approach to treat cancer. However, creation of theranostic strategies to both deliver mRNA and simultaneously detect cancer is an important unmet goal. Here, we report the development of theranostic dendrimer-based lipid nanoparticle (DLNP) system containing PEGylated BODIPY dyes (PBD) for mRNA delivery and near-infrared (NIR) imaging in vitro and in vivo. DLNPs formulated with a pH-responsive PBD-lipid produced 5- to 35-fold more functional pr  ...[more]

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