Dually Decorated Palmitate-Containing Lipid Nanoparticles for the Targeted Delivery of siRNAs against HER2 and Hsp27 in HER2<sup>+</sup> Breast Cancer
Ionizable lipid nanoparticles (LNPs) have enabled significant advances in oligonucleotide (ON) therapeutics, resulting in the approval of the short interfering RNA (siRNA)-based formulation Onpattro. However, achieving cell-specific delivery remains challenging. We have developed palmitate-containin...
保存先:
| 第一著者: | |
|---|---|
| その他の著者: | , |
| 出版事項: |
2025
|
| 主題: | |
| タグ: |
タグ追加
タグなし, このレコードへの初めてのタグを付けませんか!
|
| _version_ | 1849927644635725824 |
|---|---|
| author | Pedro Medina (454632) |
| author2 | Modesto Orozco (10295) Montserrat Terrazas (2195023) |
| author2_role | author author |
| author_facet | Pedro Medina (454632) Modesto Orozco (10295) Montserrat Terrazas (2195023) |
| author_role | author |
| dc.creator.none.fl_str_mv | Pedro Medina (454632) Modesto Orozco (10295) Montserrat Terrazas (2195023) |
| dc.date.none.fl_str_mv | 2025-11-24T14:05:50Z |
| dc.identifier.none.fl_str_mv | 10.1021/acs.jmedchem.5c02209.s001 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/dataset/Dually_Decorated_Palmitate-Containing_Lipid_Nanoparticles_for_the_Targeted_Delivery_of_siRNAs_against_HER2_and_Hsp27_in_HER2_sup_sup_Breast_Cancer/30695210 |
| dc.rights.none.fl_str_mv | CC BY-NC 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biophysics Biochemistry Medicine Cell Biology Genetics Molecular Biology Pharmacology Biotechnology Cancer Computational Biology Space Science Biological Sciences not elsewhere classified Chemical Sciences not elsewhere classified sup >+</ sup short interfering rna palmitic acid inclusion novel lnp formulation enabled significant advances containing lipid nanoparticles tumor cells compared breast cancer cells demonstrating strong potential dually decorated palmitate based targeted therapies sensitive cells targeted delivery potential use combinatorial therapies targeting peptide sirna combination results support promoting genes diverse tumors developed palmitate combination treatments achieving cell |
| dc.title.none.fl_str_mv | Dually Decorated Palmitate-Containing Lipid Nanoparticles for the Targeted Delivery of siRNAs against HER2 and Hsp27 in HER2<sup>+</sup> Breast Cancer |
| dc.type.none.fl_str_mv | Dataset info:eu-repo/semantics/publishedVersion dataset |
| description | Ionizable lipid nanoparticles (LNPs) have enabled significant advances in oligonucleotide (ON) therapeutics, resulting in the approval of the short interfering RNA (siRNA)-based formulation Onpattro. However, achieving cell-specific delivery remains challenging. We have developed palmitate-containing ionizable LNPs functionalized with (i) octreotide (Oct), targeting somatostatin receptor type 2 (SSTR2)-expressing tumor cells, and (ii) penetratin (RK16), enhancing intracellular uptake. This dually decorated LNP codelivered two siRNAs targeting tumor-promoting genes (heat shock protein 27 (Hsp27) and human epidermal growth factor receptor 2 (HER2)) into HER2<sup>+</sup> breast cancer cells, demonstrating strong potential for combinatorial therapies. Oct conferred high selectivity toward SSTR2-overexpresing HER2<sup>+</sup> breast cancer cells, even in heterogeneous environments containing nontumor cells. RK16 enhanced intracellular delivery and cytotoxicity against tumor cells compared to nonfunctionalized LNPs. Overall, our results support the potential use of this novel LNP formulation in ON-based targeted therapies. By altering the targeting peptide and siRNA combination, it could be adapted for diverse tumors and combination treatments. Additionally, palmitic acid inclusion further enhanced cytotoxicity in palmitate-sensitive cells, offering additional therapeutic advantages. |
| eu_rights_str_mv | openAccess |
| id | Manara_79facd5fa7acdd8c4e987fa829ca2094 |
| identifier_str_mv | 10.1021/acs.jmedchem.5c02209.s001 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30695210 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY-NC 4.0 |
| spelling | Dually Decorated Palmitate-Containing Lipid Nanoparticles for the Targeted Delivery of siRNAs against HER2 and Hsp27 in HER2<sup>+</sup> Breast CancerPedro Medina (454632)Modesto Orozco (10295)Montserrat Terrazas (2195023)BiophysicsBiochemistryMedicineCell BiologyGeneticsMolecular BiologyPharmacologyBiotechnologyCancerComputational BiologySpace ScienceBiological Sciences not elsewhere classifiedChemical Sciences not elsewhere classifiedsup >+</ supshort interfering rnapalmitic acid inclusionnovel lnp formulationenabled significant advancescontaining lipid nanoparticlestumor cells comparedbreast cancer cellsdemonstrating strong potentialdually decorated palmitatebased targeted therapiessensitive cellstargeted deliverypotential usecombinatorial therapiestargeting peptidesirna combinationresults supportpromoting genesdiverse tumorsdeveloped palmitatecombination treatmentsachieving cellIonizable lipid nanoparticles (LNPs) have enabled significant advances in oligonucleotide (ON) therapeutics, resulting in the approval of the short interfering RNA (siRNA)-based formulation Onpattro. However, achieving cell-specific delivery remains challenging. We have developed palmitate-containing ionizable LNPs functionalized with (i) octreotide (Oct), targeting somatostatin receptor type 2 (SSTR2)-expressing tumor cells, and (ii) penetratin (RK16), enhancing intracellular uptake. This dually decorated LNP codelivered two siRNAs targeting tumor-promoting genes (heat shock protein 27 (Hsp27) and human epidermal growth factor receptor 2 (HER2)) into HER2<sup>+</sup> breast cancer cells, demonstrating strong potential for combinatorial therapies. Oct conferred high selectivity toward SSTR2-overexpresing HER2<sup>+</sup> breast cancer cells, even in heterogeneous environments containing nontumor cells. RK16 enhanced intracellular delivery and cytotoxicity against tumor cells compared to nonfunctionalized LNPs. Overall, our results support the potential use of this novel LNP formulation in ON-based targeted therapies. By altering the targeting peptide and siRNA combination, it could be adapted for diverse tumors and combination treatments. Additionally, palmitic acid inclusion further enhanced cytotoxicity in palmitate-sensitive cells, offering additional therapeutic advantages.2025-11-24T14:05:50ZDatasetinfo:eu-repo/semantics/publishedVersiondataset10.1021/acs.jmedchem.5c02209.s001https://figshare.com/articles/dataset/Dually_Decorated_Palmitate-Containing_Lipid_Nanoparticles_for_the_Targeted_Delivery_of_siRNAs_against_HER2_and_Hsp27_in_HER2_sup_sup_Breast_Cancer/30695210CC BY-NC 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/306952102025-11-24T14:05:50Z |
| spellingShingle | Dually Decorated Palmitate-Containing Lipid Nanoparticles for the Targeted Delivery of siRNAs against HER2 and Hsp27 in HER2<sup>+</sup> Breast Cancer Pedro Medina (454632) Biophysics Biochemistry Medicine Cell Biology Genetics Molecular Biology Pharmacology Biotechnology Cancer Computational Biology Space Science Biological Sciences not elsewhere classified Chemical Sciences not elsewhere classified sup >+</ sup short interfering rna palmitic acid inclusion novel lnp formulation enabled significant advances containing lipid nanoparticles tumor cells compared breast cancer cells demonstrating strong potential dually decorated palmitate based targeted therapies sensitive cells targeted delivery potential use combinatorial therapies targeting peptide sirna combination results support promoting genes diverse tumors developed palmitate combination treatments achieving cell |
| status_str | publishedVersion |
| title | Dually Decorated Palmitate-Containing Lipid Nanoparticles for the Targeted Delivery of siRNAs against HER2 and Hsp27 in HER2<sup>+</sup> Breast Cancer |
| title_full | Dually Decorated Palmitate-Containing Lipid Nanoparticles for the Targeted Delivery of siRNAs against HER2 and Hsp27 in HER2<sup>+</sup> Breast Cancer |
| title_fullStr | Dually Decorated Palmitate-Containing Lipid Nanoparticles for the Targeted Delivery of siRNAs against HER2 and Hsp27 in HER2<sup>+</sup> Breast Cancer |
| title_full_unstemmed | Dually Decorated Palmitate-Containing Lipid Nanoparticles for the Targeted Delivery of siRNAs against HER2 and Hsp27 in HER2<sup>+</sup> Breast Cancer |
| title_short | Dually Decorated Palmitate-Containing Lipid Nanoparticles for the Targeted Delivery of siRNAs against HER2 and Hsp27 in HER2<sup>+</sup> Breast Cancer |
| title_sort | Dually Decorated Palmitate-Containing Lipid Nanoparticles for the Targeted Delivery of siRNAs against HER2 and Hsp27 in HER2<sup>+</sup> Breast Cancer |
| topic | Biophysics Biochemistry Medicine Cell Biology Genetics Molecular Biology Pharmacology Biotechnology Cancer Computational Biology Space Science Biological Sciences not elsewhere classified Chemical Sciences not elsewhere classified sup >+</ sup short interfering rna palmitic acid inclusion novel lnp formulation enabled significant advances containing lipid nanoparticles tumor cells compared breast cancer cells demonstrating strong potential dually decorated palmitate based targeted therapies sensitive cells targeted delivery potential use combinatorial therapies targeting peptide sirna combination results support promoting genes diverse tumors developed palmitate combination treatments achieving cell |