期刊
JOURNAL OF CONTROLLED RELEASE
卷 325, 期 -, 页码 198-205出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2020.06.030
关键词
mRNA delivery; Lipid nanoparticles; Dendrimers; NIR imaging; Theranostics
资金
- Department of Defense [CA150245P3]
- National Institutes of Health (NIH)National Cancer Institute (NCI)Cancer Center Support Grant (CCSG)
- NIH National Institute of Biomedical Imaging and Bioengineering (NIBIB) [R01 EB025192-01A1]
- American Cancer Society (ACS) [RSG-17-01201]
- Cystic Fibrosis Foundation (CFF) [SIEGWA18XX0]
- Cancer Prevention and Research Institute of Texas (CPRIT) [R1212, RP190251]
- Welch Foundation [I-1855]
- Cancer Prevention and Research Institute of Texas (CPRIT) Training Grant [RP160157]
- NSFC [21907054]
- Nankai University [ZB19100136]
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.
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