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- Publisher Website: 10.1016/j.canlet.2021.09.031
- Scopus: eid_2-s2.0-85115940723
- PMID: 34571084
- WOS: WOS:000708799100001
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Article: Thermal-sensitive lipid nanoparticles potentiate anti-PD therapy through enhancing drug penetration and T lymphocytes infiltration in metastatic tumor
Title | Thermal-sensitive lipid nanoparticles potentiate anti-PD therapy through enhancing drug penetration and T lymphocytes infiltration in metastatic tumor |
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Authors | |
Keywords | Anti-PD therapy Responsive drug release Laser-enhanced immunotherapy Cold tumor Tumor metastasis |
Issue Date | 2021 |
Publisher | Elsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canlet |
Citation | Cancer Letters, 2021, v. 522, p. 238-254 How to Cite? |
Abstract | The response rate of anti-PD therapy in most cancer patients remains low. Therapeutic drug and tumor-infiltrating lymphocytes (TILs) are usually obstructed by the stromal region within tumor microenvironment (TME) rather than distributed around tumor cells, thus unable to induce the immune response of cytotoxic T cells. Here, we constructed the cationic thermosensitive lipid nanoparticles IR780/DPPC/BMS by introducing cationic NIR photosensitizer IR-780 iodide (IR780) modified lipid components, thermosensitive lipid DPPC and PD-1/PD-L1 inhibitor BMS202 (BMS). Upon laser irradiation, IR780/DPPC/BMS penetrated into deep tumor, and reduced cancer-associated fibroblasts (CAFs) around tumor cells to remodel the spatial distribution of TILs in TME. Interestingly, the cationic IR780/DPPC/BMS could capture released tumor-associated antigens (TAAs), thereby enhancing the antigen-presenting ability of DCs to activate cytotoxic T lymphocytes. Moreover, IR780/DPPC/BMS initiated gel-liquid crystal phase transition under laser irradiation, accelerating the disintegration of lipid bilayer structure and leading to the responsive release of BMS, which would reverse the tumor immunosuppression state by blocking PD-1/PD-L1 pathway for a long term. This combination treatment can synergistically exert the antitumor immune response and inhibit the tumor growth and metastasis. |
Persistent Identifier | http://hdl.handle.net/10722/309090 |
ISSN | 2023 Impact Factor: 9.1 2023 SCImago Journal Rankings: 2.595 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Tan, YN | - |
dc.contributor.author | Li, YP | - |
dc.contributor.author | Huang, J | - |
dc.contributor.author | Luo, M | - |
dc.contributor.author | Li, SS | - |
dc.contributor.author | Lee, WMA | - |
dc.contributor.author | Hu, FQ | - |
dc.contributor.author | Guan, XY | - |
dc.date.accessioned | 2021-12-14T01:40:27Z | - |
dc.date.available | 2021-12-14T01:40:27Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Cancer Letters, 2021, v. 522, p. 238-254 | - |
dc.identifier.issn | 0304-3835 | - |
dc.identifier.uri | http://hdl.handle.net/10722/309090 | - |
dc.description.abstract | The response rate of anti-PD therapy in most cancer patients remains low. Therapeutic drug and tumor-infiltrating lymphocytes (TILs) are usually obstructed by the stromal region within tumor microenvironment (TME) rather than distributed around tumor cells, thus unable to induce the immune response of cytotoxic T cells. Here, we constructed the cationic thermosensitive lipid nanoparticles IR780/DPPC/BMS by introducing cationic NIR photosensitizer IR-780 iodide (IR780) modified lipid components, thermosensitive lipid DPPC and PD-1/PD-L1 inhibitor BMS202 (BMS). Upon laser irradiation, IR780/DPPC/BMS penetrated into deep tumor, and reduced cancer-associated fibroblasts (CAFs) around tumor cells to remodel the spatial distribution of TILs in TME. Interestingly, the cationic IR780/DPPC/BMS could capture released tumor-associated antigens (TAAs), thereby enhancing the antigen-presenting ability of DCs to activate cytotoxic T lymphocytes. Moreover, IR780/DPPC/BMS initiated gel-liquid crystal phase transition under laser irradiation, accelerating the disintegration of lipid bilayer structure and leading to the responsive release of BMS, which would reverse the tumor immunosuppression state by blocking PD-1/PD-L1 pathway for a long term. This combination treatment can synergistically exert the antitumor immune response and inhibit the tumor growth and metastasis. | - |
dc.language | eng | - |
dc.publisher | Elsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canlet | - |
dc.relation.ispartof | Cancer Letters | - |
dc.subject | Anti-PD therapy | - |
dc.subject | Responsive drug release | - |
dc.subject | Laser-enhanced immunotherapy | - |
dc.subject | Cold tumor | - |
dc.subject | Tumor metastasis | - |
dc.title | Thermal-sensitive lipid nanoparticles potentiate anti-PD therapy through enhancing drug penetration and T lymphocytes infiltration in metastatic tumor | - |
dc.type | Article | - |
dc.identifier.email | Huang, J: jdhuang@hku.hk | - |
dc.identifier.email | Lee, WMA: awmlee@hkucc.hku.hk | - |
dc.identifier.email | Guan, XY: xyguan@hku.hk | - |
dc.identifier.authority | Huang, J=rp00451 | - |
dc.identifier.authority | Lee, WMA=rp02056 | - |
dc.identifier.authority | Guan, XY=rp00454 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.canlet.2021.09.031 | - |
dc.identifier.pmid | 34571084 | - |
dc.identifier.scopus | eid_2-s2.0-85115940723 | - |
dc.identifier.hkuros | 331063 | - |
dc.identifier.volume | 522 | - |
dc.identifier.spage | 238 | - |
dc.identifier.epage | 254 | - |
dc.identifier.isi | WOS:000708799100001 | - |
dc.publisher.place | Ireland | - |