PMID- 36015198
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220830
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 14
IP  - 8
DP  - 2022 Jul 28
TI  - mRNA-Loaded Lipid Nanoparticles Targeting Dendritic Cells for Cancer 
      Immunotherapy.
LID - 10.3390/pharmaceutics14081572 [doi]
LID - 1572
AB  - Dendritic cells (DCs) are attractive antigen-presenting cells to be targeted for 
      vaccinations. However, the systemic delivery of mRNA to DCs is hampered by 
      technical challenges. We recently reported that it is possible to regulate the 
      size of RNA-loaded lipid nanoparticles (LNPs) to over 200 nm with the addition of 
      salt during their formation when a microfluidic device is used and that larger 
      LNPs delivered RNA more efficiently and in greater numbers to splenic DCs 
      compared to the smaller counterparts. In this study, we report on the in vivo 
      optimization of mRNA-loaded LNPs for use in vaccines. The screening included a 
      wide range of methods for controlling particle size in addition to the selection 
      of an appropriate lipid type and its composition. The results showed a clear 
      correlation between particle size, uptake and gene expression activity in splenic 
      DCs and indicated that a size range from 200 to 500 nm is appropriate for use in 
      targeting splenic DCs. It was also found that it was difficult to predict the 
      transgene expression activity and the potency of mRNA vaccines in splenic DCs 
      using the whole spleen. A-11-LNP, which was found to be the optimal formulation, 
      induced better transgene expression activity and maturation in DCs and induced 
      clear therapeutic antitumor effects in an E.G7-OVA tumor model compared to two 
      clinically relevant LNP formulations.
FAU - Sasaki, Kosuke
AU  - Sasaki K
AD  - Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical 
      Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-Ku, Sapporo 060-0812, 
      Japan.
FAU - Sato, Yusuke
AU  - Sato Y
AUID- ORCID: 0000-0003-0913-7815
AD  - Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical 
      Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-Ku, Sapporo 060-0812, 
      Japan.
FAU - Okuda, Kento
AU  - Okuda K
AD  - Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical 
      Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-Ku, Sapporo 060-0812, 
      Japan.
FAU - Iwakawa, Kazuki
AU  - Iwakawa K
AD  - Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical 
      Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-Ku, Sapporo 060-0812, 
      Japan.
FAU - Harashima, Hideyoshi
AU  - Harashima H
AD  - Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical 
      Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-Ku, Sapporo 060-0812, 
      Japan.
LA  - eng
GR  - Support Program for Frontier Research/Hokkaido University/
GR  - Medical and Pharmaceutical Research/The Mochida Memorial Foundation/
GR  - Research Expenses/The Ministry of Education, Culture, Sports, Science and 
      Technology/
PT  - Journal Article
DEP - 20220728
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC9413374
OTO - NOTNLM
OT  - cancer immunotherapy
OT  - delivery
OT  - dendritic cells
OT  - lipid nanoparticles
OT  - mRNA
OT  - particle size
COIS- The authors declare no conflict of interest.
EDAT- 2022/08/27 06:00
MHDA- 2022/08/27 06:01
PMCR- 2022/07/28
CRDT- 2022/08/26 01:41
PHST- 2022/07/09 00:00 [received]
PHST- 2022/07/26 00:00 [revised]
PHST- 2022/07/26 00:00 [accepted]
PHST- 2022/08/26 01:41 [entrez]
PHST- 2022/08/27 06:00 [pubmed]
PHST- 2022/08/27 06:01 [medline]
PHST- 2022/07/28 00:00 [pmc-release]
AID - pharmaceutics14081572 [pii]
AID - pharmaceutics-14-01572 [pii]
AID - 10.3390/pharmaceutics14081572 [doi]
PST - epublish
SO  - Pharmaceutics. 2022 Jul 28;14(8):1572. doi: 10.3390/pharmaceutics14081572.