Use of Stromal Intervention and Exogenous Neoantigen Vaccination to Boost Pancreatic Cancer Chemo-Immunotherapy by Nanocarriers
Despite the formidable treatment challenges of pancreatic ductal adenocarcinoma (PDAC), considerable progress has been made in improving drug delivery via pioneering nanocarriers. These innovations are geared towards overcoming the obstacles presented by dysplastic stroma and fostering anti-PDAC imm...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-10-01
|
| Series: | Bioengineering |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2306-5354/10/10/1205 |
| _version_ | 1797574682803699712 |
|---|---|
| author | Saborni Chattopadhyay Yu-Pei Liao Xiang Wang André E. Nel |
| author_facet | Saborni Chattopadhyay Yu-Pei Liao Xiang Wang André E. Nel |
| author_sort | Saborni Chattopadhyay |
| collection | DOAJ |
| description | Despite the formidable treatment challenges of pancreatic ductal adenocarcinoma (PDAC), considerable progress has been made in improving drug delivery via pioneering nanocarriers. These innovations are geared towards overcoming the obstacles presented by dysplastic stroma and fostering anti-PDAC immune reactions. We are currently conducting research aimed at enhancing chemotherapy to stimulate anti-tumor immunity by inducing immunogenic cell death (ICD). This is accomplished using lipid bilayer-coated nanocarriers, which enable the attainment of synergistic results. Noteworthy examples include liposomes and lipid-coated mesoporous silica nanoparticles known as “silicasomes”. These nanocarriers facilitate remote chemotherapy loading, as well as the seamless integration of immunomodulators into the lipid bilayer. In this communication, we elucidate innovative ways for further improving chemo-immunotherapy. The first is the development of a liposome platform engineered by the remote loading of irinotecan while incorporating a pro-resolving lipoxin in the lipid bilayer. This carrier interfered in stromal collagen deposition, as well as boosting the irinotecan-induced ICD response. The second approach was to synthesize polymer nanoparticles for the delivery of mutated KRAS peptides in conjunction with a TLR7/8 agonist. The dual delivery vaccine particle boosted the generation of antigen-specific cytotoxic T-cells that are recruited to lymphoid structures at the cancer site, with a view to strengthening the endogenous vaccination response achieved by chemo-immunotherapy. |
| first_indexed | 2024-03-10T21:25:47Z |
| format | Article |
| id | doaj.art-b7f7b8a21d244039a0e61aeee9d4280a |
| institution | Directory Open Access Journal |
| issn | 2306-5354 |
| language | English |
| last_indexed | 2024-03-10T21:25:47Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Bioengineering |
| spelling | doaj.art-b7f7b8a21d244039a0e61aeee9d4280a2023-11-19T15:42:30ZengMDPI AGBioengineering2306-53542023-10-011010120510.3390/bioengineering10101205Use of Stromal Intervention and Exogenous Neoantigen Vaccination to Boost Pancreatic Cancer Chemo-Immunotherapy by NanocarriersSaborni Chattopadhyay0Yu-Pei Liao1Xiang Wang2André E. Nel3California NanoSystems Institute, University of California, Los Angeles, CA 90095, USACalifornia NanoSystems Institute, University of California, Los Angeles, CA 90095, USACalifornia NanoSystems Institute, University of California, Los Angeles, CA 90095, USACalifornia NanoSystems Institute, University of California, Los Angeles, CA 90095, USADespite the formidable treatment challenges of pancreatic ductal adenocarcinoma (PDAC), considerable progress has been made in improving drug delivery via pioneering nanocarriers. These innovations are geared towards overcoming the obstacles presented by dysplastic stroma and fostering anti-PDAC immune reactions. We are currently conducting research aimed at enhancing chemotherapy to stimulate anti-tumor immunity by inducing immunogenic cell death (ICD). This is accomplished using lipid bilayer-coated nanocarriers, which enable the attainment of synergistic results. Noteworthy examples include liposomes and lipid-coated mesoporous silica nanoparticles known as “silicasomes”. These nanocarriers facilitate remote chemotherapy loading, as well as the seamless integration of immunomodulators into the lipid bilayer. In this communication, we elucidate innovative ways for further improving chemo-immunotherapy. The first is the development of a liposome platform engineered by the remote loading of irinotecan while incorporating a pro-resolving lipoxin in the lipid bilayer. This carrier interfered in stromal collagen deposition, as well as boosting the irinotecan-induced ICD response. The second approach was to synthesize polymer nanoparticles for the delivery of mutated KRAS peptides in conjunction with a TLR7/8 agonist. The dual delivery vaccine particle boosted the generation of antigen-specific cytotoxic T-cells that are recruited to lymphoid structures at the cancer site, with a view to strengthening the endogenous vaccination response achieved by chemo-immunotherapy.https://www.mdpi.com/2306-5354/10/10/1205pancreatic cancertumor stromairinotecanlipoxinsKRAS vaccinationtertiary lymphoid structures |
| spellingShingle | Saborni Chattopadhyay Yu-Pei Liao Xiang Wang André E. Nel Use of Stromal Intervention and Exogenous Neoantigen Vaccination to Boost Pancreatic Cancer Chemo-Immunotherapy by Nanocarriers Bioengineering pancreatic cancer tumor stroma irinotecan lipoxins KRAS vaccination tertiary lymphoid structures |
| title | Use of Stromal Intervention and Exogenous Neoantigen Vaccination to Boost Pancreatic Cancer Chemo-Immunotherapy by Nanocarriers |
| title_full | Use of Stromal Intervention and Exogenous Neoantigen Vaccination to Boost Pancreatic Cancer Chemo-Immunotherapy by Nanocarriers |
| title_fullStr | Use of Stromal Intervention and Exogenous Neoantigen Vaccination to Boost Pancreatic Cancer Chemo-Immunotherapy by Nanocarriers |
| title_full_unstemmed | Use of Stromal Intervention and Exogenous Neoantigen Vaccination to Boost Pancreatic Cancer Chemo-Immunotherapy by Nanocarriers |
| title_short | Use of Stromal Intervention and Exogenous Neoantigen Vaccination to Boost Pancreatic Cancer Chemo-Immunotherapy by Nanocarriers |
| title_sort | use of stromal intervention and exogenous neoantigen vaccination to boost pancreatic cancer chemo immunotherapy by nanocarriers |
| topic | pancreatic cancer tumor stroma irinotecan lipoxins KRAS vaccination tertiary lymphoid structures |
| url | https://www.mdpi.com/2306-5354/10/10/1205 |
| work_keys_str_mv | AT sabornichattopadhyay useofstromalinterventionandexogenousneoantigenvaccinationtoboostpancreaticcancerchemoimmunotherapybynanocarriers AT yupeiliao useofstromalinterventionandexogenousneoantigenvaccinationtoboostpancreaticcancerchemoimmunotherapybynanocarriers AT xiangwang useofstromalinterventionandexogenousneoantigenvaccinationtoboostpancreaticcancerchemoimmunotherapybynanocarriers AT andreenel useofstromalinterventionandexogenousneoantigenvaccinationtoboostpancreaticcancerchemoimmunotherapybynanocarriers |