The Transcriptional Response to Lung-Targeting Lipid Nanoparticles <i>in Vivo</i>

Radmand, Afsane; Lokugamage, Melissa P.; Kim, Hye-Jin; Dobrowolski, Curtis; Zenhausern, Ryan; Loughrey, David; Huayamares, Sebastian G.; Hatit, Marine Z. C.; Ni, Huanzhen; Cid, Ada Del; Sanchez, Alejandro J. Da Silva; Paunovska, Kalina; Echeverri, Elisa Schrader; Shajii, Aram; Peck, Hannah E.; Santangelo, Philip J.; Dahlman, James E.

doi:10.1021/acs.nanolett.2c04479

Cited by 35 publications

(30 citation statements)

References 40 publications

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“…Although IFNBCOL01 enables tumor cells and resident cells to express IFNβ locally and is expected to have less systemic toxicity than the systemic IFNα protein therapy, a tumor-targeting IFNBCOL01 certainly represents a more desired agent. Promising progress has been made in developing the next generation of lipid nanoparticles that are tissue-selective. − Further studies are therefore needed to develop a tumor-selective fourth generation IFN-I agent for human colon cancer immunotherapy.…”

Section: Resultsmentioning

confidence: 99%

“…Lipid nanoparticle has recently reemerged as an effective delivery vehicle for delivering nucleic acid into mammalian cells to achieve therapeutic efficacy. − The coronavirus disease 2019 (COVID-19) mRNA vaccine represents a turning point and breakthrough in lipid-nanoparticle-nucleic-acid-based immunotherapy for a human disease. mRNA vaccines are based on lipid nanoparticle delivery of the cargo mRNA into mammalian cells through lipid-mediated transfection and subsequent translation of the mRNA into a functional peptide to achieve therapeutic efficacy .…”

Section: Introductionmentioning

confidence: 99%

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Delivery of Interferon β-Encoding Plasmid via Lipid Nanoparticle Restores Interferon β Expression to Enhance Antitumor Immunity in Colon Cancer

Yang,

Bo,

Liang

et al. 2024

ACS Nano

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Type I interferon (IFN-I) plays a critical role in host cancer immunosurveillance, but its expression is often impaired in the tumor microenvironment. We aimed at testing the hypothesis that cationic lipid nanoparticle delivery of interferon β (IFNβ)-encoding plasmid to tumors is effective in restoring IFNβ expression to suppress tumor immune evasion. We determined that IFN-I function in tumor suppression depends on the host immune cells. IFN-I activates the expression of Cxcl9 and Cxcl10 to enhance T cell tumor infiltration. RNA-Seq detected a low level of IFNα13 and IFNβ in colon tumor tissue. scRNA-Seq revealed that IFNβ is expressed in immune cell subsets in non-neoplastic human tissues and to a lesser degree in human colon tumor tissues. Forced expression of IFNα13 and IFNβ in colon tumor cells upregulates major histocompatibility complex I (MHC I) expression and suppresses colon tumor growth in vivo. In human cancer patients, IFNβ expression is positively correlated with human leukocyte antigen (HLA) expression, and IFN-I signaling activation correlates with the patient response to PD-1 blockade immunotherapy. To translate this finding to colon cancer immunotherapy, we formulated a 1,2-dioleoyl-3-trimethylammonium propane (DOTAP)-cholesterol-encapsulated IFNβencoding plasmid (IFNBCOL01). IFNBCOL01 transfects colon tumor cells to express IFNβ to increase the level of MHC I expression. IFNBCOL01 therapy transfects tumor cells and tumor-infiltrating immune cells to produce IFNβ to activate MHC I and granzyme B expression and inhibits colon tumor growth in mice. Our data determine that lipid nanoparticle delivery of IFNβ-encoding plasmid DNA enhances tumor immunogenicity and T cell effector function to suppress colon tumor growth in vivo.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Delivery of Interferon β-Encoding Plasmid via Lipid Nanoparticle Restores Interferon β Expression to Enhance Antitumor Immunity in Colon Cancer

Yang,

Bo,

Liang

et al. 2024

ACS Nano

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“…In recent years, preclinical research has highlighted the efficacy of lipid nanoparticle (LNP) delivery systems for treating pulmonary diseases. For example, Arikayce is an FDA-approved inhalation LNP therapy for treating Mycobacterium avium complex infections. , …”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Anticancer and Antibacterial Properties of Curcumin-Loaded Mannosylated Solid Lipid Nanoparticles for the Treatment of Lung Diseases

Chae,

Choi,

Hong

et al. 2024

ACS Appl. Bio Mater.

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Lung cancer and Mycobacterium avium complex infection are lung diseases associated with high incidence and mortality rates. Most conventional anticancer drugs and antibiotics have certain limitations, including high drug resistance rates and adverse effects. Herein, we aimed to synthesize mannose surface-modified solid lipid nanoparticles (SLNs) loaded with curcumin (Man-CUR SLN) for the effective treatment of lung disease. The synthesized Man-CUR SLNs were analyzed using various instrumental techniques for structural and physicochemical characterization. Loading curcumin into SLNs improved the encapsulation efficiency and drug release capacity, as demonstrated by high-performance liquid chromatography analysis. Furthermore, we characterized the anticancer effect of curcumin using the A549 lung cancer cell line. Cells treated with Man-CUR SLN exhibited an increased cellular uptake and cytotoxicity. Moreover, treatment with free CUR could more effectively reduce cancer migration than treatment with Man-CUR SLNs. Similarly, free curcumin elicited a stronger apoptosis-inducing effect than that of Man-CUR SLNs, as demonstrated by reverse transcriptionquantitative PCR analysis. Finally, we examined the antibacterial effects of free curcumin and Man-CUR SLNs against Mycobacterium intracellulare (M.i.) and M.i.-infected macrophages, revealing that Man-CUR SLNs exerted the strongest antibacterial effect. Collectively, these findings indicate that mannose-receptor-targeted curcumin delivery using lipid nanoparticles could be effective in treating lung diseases. Accordingly, this drug delivery system can be used to target a variety of cancers and immune cells.

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“…However, this method fails to facilitate controlled cell-specific delivery, and as a result, most intravenously (IV) administered LNPs that target the lungs end up in the pulmonary endothelium rather than the epithelium . For example, after screening 137 LNPs for lung delivery, Radmand et al found that the top-performing cationic mRNA-carrying (messenger RNA-carrying) LNP formulation led to transcription in about 100% of the endothelial cells but only in about 20% of the type I pneumocytes and virtually in none of the type II pneumocytes in a mouse model . Other studies similarly found a high tropism for endothelial cells and even lower expression in lung epithelial cells after the IV injection of mRNA-carrying LNPs. , …”

mentioning

confidence: 99%

“…4 For example, after screening 137 LNPs for lung delivery, Radmand et al found that the top-performing cationic mRNA-carrying (messenger RNA-carrying) LNP formulation led to transcription in about 100% of the endothelial cells but only in about 20% of the type I pneumocytes and virtually in none of the type II pneumocytes in a mouse model. 5 Other studies similarly found a high tropism for endothelial cells and even lower expression in lung epithelial cells after the IV injection of mRNA-carrying LNPs. 6,7 Unfortunately, most respiratory diseases are neither originated nor localized in the pulmonary endothelium.…”

mentioning

confidence: 99%