{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:17:43Z","timestamp":1790144263726,"version":"4.0.1"},"reference-count":22,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T00:00:00Z","timestamp":1581465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21875124"],"award-info":[{"award-number":["21875124"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Cutaneous melanoma is the most aggressive skin cancer with notorious drug resistance. Inhibition of immune checkpoint molecules is one of the most promising approaches for cancer therapy. Herein, we show that RNAi mediated silencing of STAT3 expression in the tumor tissue robustly inhibit tumor growth in B16F10 mouse model of melanoma. We designed a peptidomimetic-based lipid nanoparticles (LNPs) for the delivery of siRNA in mouse model of melanoma. When systemically administered, the novel formulation (denote DoCh) preferentially delivered siRNA to the tumor tissue. Remarkably, sequential intravenous injections of siRNA against STAT3 induced profound silencing of STAT3 expression in tumor tissue, which resulted in significant downregulation of PD-L1, leading to significant inhibition of tumor growth through inhibition of tumor immune checkpoint. Moreover, DoCh-mediated siRNA delivery did not show noticeable damage to the major organs. Collectively, our data demonstrated that DoCh LNP is a promising tumor-targeted siRNA delivery system.<\/jats:p>","DOI":"10.3390\/biom10020285","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T10:49:16Z","timestamp":1582282156000},"page":"285","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Silencing of STAT3 via Peptidomimetic LNP-Mediated Systemic Delivery of RNAi Downregulates PD-L1 and Inhibits Melanoma Growth"],"prefix":"10.3390","volume":"10","author":[{"given":"Ehexige","family":"Ehexige","sequence":"first","affiliation":[{"name":"Institute of Mongolian Medicinal Chemistry, School of Chemistry &amp; Chemical Engineering, Inner Mongolia University, Hohhot 010020, Inner Mongolia, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Bao","sequence":"additional","affiliation":[{"name":"Institute of Mongolian Medicinal Chemistry, School of Chemistry &amp; Chemical Engineering, Inner Mongolia University, Hohhot 010020, Inner Mongolia, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purevbat","family":"Bazarjav","sequence":"additional","affiliation":[{"name":"Institute of Mongolian Medicinal Chemistry, School of Chemistry &amp; Chemical Engineering, Inner Mongolia University, Hohhot 010020, Inner Mongolia, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Mongolian Medicinal Chemistry, School of Chemistry &amp; Chemical Engineering, Inner Mongolia University, Hohhot 010020, Inner Mongolia, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Xiao","sequence":"additional","affiliation":[{"name":"Institute of Mongolian Medicinal Chemistry, School of Chemistry &amp; Chemical Engineering, Inner Mongolia University, Hohhot 010020, Inner Mongolia, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqin","family":"Han","sequence":"additional","affiliation":[{"name":"Institute of Mongolian Medicinal Chemistry, School of Chemistry &amp; Chemical Engineering, Inner Mongolia University, Hohhot 010020, Inner Mongolia, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5479-182X","authenticated-orcid":false,"given":"Huricha","family":"Baigude","sequence":"additional","affiliation":[{"name":"Institute of Mongolian Medicinal Chemistry, School of Chemistry &amp; Chemical Engineering, Inner Mongolia University, Hohhot 010020, Inner Mongolia, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/j.cell.2018.04.012","article-title":"An Acquired Vulnerability of Drug-Resistant Melanoma with Therapeutic Potential","volume":"173","author":"Wang","year":"2018","journal-title":"Cell"},{"key":"ref_2","first-page":"357","article-title":"Early detection and treatment of skin cancer","volume":"62","author":"Jerant","year":"2000","journal-title":"Am. Fam. Physician"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1093\/jnci\/93.9.678","article-title":"Recent trends in cutaneous melanoma incidence among whites in the United States","volume":"93","author":"Jemal","year":"2001","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_4","first-page":"93","article-title":"Human melanoma: Drug resistance","volume":"161","author":"Helmbach","year":"2003","journal-title":"Skin Stem Cells"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/nature00766","article-title":"Mutations of the BRAF gene in human cancer","volume":"417","author":"Davies","year":"2002","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nature24040","article-title":"PAK signalling drives acquired drug resistance to MAPK inhibitors in BRAF-mutant melanomas","volume":"550","author":"Lu","year":"2017","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/S0140-6736(12)60868-X","article-title":"Dabrafenib in BRAF-mutated metastatic melanoma: A multicentre, open-label, phase 3 randomised controlled trial","volume":"380","author":"Hauschild","year":"2012","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.cell.2017.01.010","article-title":"Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma","volume":"168","author":"Hugo","year":"2017","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15816","DOI":"10.1073\/pnas.1016152108","article-title":"Delivery of siRNA and other macromolecules into skin and cells using a peptide enhancer","volume":"108","author":"Hsu","year":"2011","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3435","DOI":"10.1016\/j.biomaterials.2013.12.079","article-title":"Non-covalently functionalized single-walled carbon nanotube for topical siRNA delivery into melanoma","volume":"35","author":"Siu","year":"2014","journal-title":"Biomaterials"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.jconrel.2016.03.010","article-title":"Development of edge-activated liposomes for siRNA delivery to human basal epidermis for melanoma therapy","volume":"228","author":"Dorrani","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nrc3818","article-title":"Revisiting STAT3 signalling in cancer: New and unexpected biological functions","volume":"14","author":"Yu","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1016\/j.biomaterials.2009.11.003","article-title":"The induction of tumor apoptosis in B16 melanoma following STAT3 siRNA delivery with a lipid-substituted polyethylenimine","volume":"31","author":"Alshamsan","year":"2010","journal-title":"Biomaterials"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1038\/s41598-018-19463-2","article-title":"Intradermal delivery of STAT3 siRNA to treat melanoma via dissolving microneedles","volume":"8","author":"Pan","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.colsurfb.2016.05.076","article-title":"Transcutaneous iontophoretic delivery of STAT3 siRNA using layer-by-layer chitosan coated gold nanoparticles to treat melanoma","volume":"146","author":"Labala","year":"2016","journal-title":"Colloids Surfaces Biointerfaces"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"14463","DOI":"10.1021\/acsami.8b02073","article-title":"Design of Mannose-Functionalized Curdlan Nanoparticles for Macrophage-Targeted siRNA Delivery","volume":"10","author":"Ganbold","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"21521","DOI":"10.1021\/acsami.5b06792","article-title":"Cell Type-Specific Delivery of RNAi by Ligand-Functionalized Curdlan Nanoparticles: Balancing the Receptor Mediation and the Charge Motivation","volume":"7","author":"Wu","year":"2015","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ehexige, E., Ganbold, T., Yu, X., Han, S., and Baigude, H. (2019). Design of Peptidomimetic Functionalized Cholesterol Based Lipid Nanoparticles for Efficient Delivery of Therapeutic Nucleic Acids. Molecules, 24.","DOI":"10.3390\/molecules24183413"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7638","DOI":"10.1021\/acsami.5b12144","article-title":"Design of Highly Potent Lipid-Functionalized Peptidomimetics for Efficient in Vivo siRNA Delivery","volume":"8","author":"Xiao","year":"2016","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_20","first-page":"5597","article-title":"Head group configuration increases the biocompatibility of cationic lipids for nucleic acid delivery","volume":"5","author":"Gerile","year":"2017","journal-title":"J. Mater. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5779","DOI":"10.1007\/s00216-017-0527-z","article-title":"Zeta potential: A case study of cationic, anionic, and neutral liposomes","volume":"409","author":"Smith","year":"2017","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.omtn.2018.08.003","article-title":"siRNA Knockdown of RRM2 Effectively Suppressed Pancreatic Tumor Growth Alone or Synergistically with Doxorubicin","volume":"12","author":"Zheng","year":"2018","journal-title":"Mol. Ther. Nucleic Acids"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/2\/285\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:57:14Z","timestamp":1760173034000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/2\/285"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,12]]},"references-count":22,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["biom10020285"],"URL":"https:\/\/doi.org\/10.3390\/biom10020285","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,12]]}}}