A Squalene-Based Nanoemulsion for Therapeutic Delivery of Resiquimod
Agonists for toll-like receptors (TLRs) have shown promising activities against cancer. In the present study, a squalene-based nanoemulsion (NE) was loaded with resiquimod, a TLR7/8 agonist for therapeutic delivery. R848 NE was developed and characterized for long-term stability. In vitro and in viv...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/12/2060 |
| _version_ | 1797501514988650496 |
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| author | Zhongkun Zhang Jimmy Chun-Tien Kuo Chi Zhang Yirui Huang Zerui Zhou Robert J. Lee |
| author_facet | Zhongkun Zhang Jimmy Chun-Tien Kuo Chi Zhang Yirui Huang Zerui Zhou Robert J. Lee |
| author_sort | Zhongkun Zhang |
| collection | DOAJ |
| description | Agonists for toll-like receptors (TLRs) have shown promising activities against cancer. In the present study, a squalene-based nanoemulsion (NE) was loaded with resiquimod, a TLR7/8 agonist for therapeutic delivery. R848 NE was developed and characterized for long-term stability. In vitro and in vivo antitumor immunity of R848 NE were also evaluated in combination with SD-101, a CpG-containing TLR9 agonist. In vitro studies demonstrated strong long-term stability and immune responses to R848 NE. When combined with SD-101, strong antitumor activity was observed in MC38 murine colon carcinoma model with over 80% tumor growth inhibition. The combination treatment showed a 4-fold increase in systemic TNFa production and a 2.6-fold increase in Cd8a expression in tumor tissues, suggesting strong cell-mediated immune responses against the tumor. The treatment not only demonstrated a strong antitumor immunity by TLR7/8 and TLR9 activations but also induced PD-L1 upregulation in tumors, suggesting a potential therapeutic synergy with immune checkpoint inhibitors. |
| first_indexed | 2024-03-10T03:19:31Z |
| format | Article |
| id | doaj.art-7b532bb8858e435da9af46ca036844c5 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T03:19:31Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-7b532bb8858e435da9af46ca036844c52023-11-23T10:05:24ZengMDPI AGPharmaceutics1999-49232021-12-011312206010.3390/pharmaceutics13122060A Squalene-Based Nanoemulsion for Therapeutic Delivery of ResiquimodZhongkun Zhang0Jimmy Chun-Tien Kuo1Chi Zhang2Yirui Huang3Zerui Zhou4Robert J. Lee5Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USADivision of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USADivision of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USADivision of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USADivision of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USADivision of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USAAgonists for toll-like receptors (TLRs) have shown promising activities against cancer. In the present study, a squalene-based nanoemulsion (NE) was loaded with resiquimod, a TLR7/8 agonist for therapeutic delivery. R848 NE was developed and characterized for long-term stability. In vitro and in vivo antitumor immunity of R848 NE were also evaluated in combination with SD-101, a CpG-containing TLR9 agonist. In vitro studies demonstrated strong long-term stability and immune responses to R848 NE. When combined with SD-101, strong antitumor activity was observed in MC38 murine colon carcinoma model with over 80% tumor growth inhibition. The combination treatment showed a 4-fold increase in systemic TNFa production and a 2.6-fold increase in Cd8a expression in tumor tissues, suggesting strong cell-mediated immune responses against the tumor. The treatment not only demonstrated a strong antitumor immunity by TLR7/8 and TLR9 activations but also induced PD-L1 upregulation in tumors, suggesting a potential therapeutic synergy with immune checkpoint inhibitors.https://www.mdpi.com/1999-4923/13/12/2060nanoemulsionsTLR agonistssolid tumorsSD-101resiquimod |
| spellingShingle | Zhongkun Zhang Jimmy Chun-Tien Kuo Chi Zhang Yirui Huang Zerui Zhou Robert J. Lee A Squalene-Based Nanoemulsion for Therapeutic Delivery of Resiquimod Pharmaceutics nanoemulsions TLR agonists solid tumors SD-101 resiquimod |
| title | A Squalene-Based Nanoemulsion for Therapeutic Delivery of Resiquimod |
| title_full | A Squalene-Based Nanoemulsion for Therapeutic Delivery of Resiquimod |
| title_fullStr | A Squalene-Based Nanoemulsion for Therapeutic Delivery of Resiquimod |
| title_full_unstemmed | A Squalene-Based Nanoemulsion for Therapeutic Delivery of Resiquimod |
| title_short | A Squalene-Based Nanoemulsion for Therapeutic Delivery of Resiquimod |
| title_sort | squalene based nanoemulsion for therapeutic delivery of resiquimod |
| topic | nanoemulsions TLR agonists solid tumors SD-101 resiquimod |
| url | https://www.mdpi.com/1999-4923/13/12/2060 |
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