Double-targeted liposomes coated with matrix metallopeptidase-2-responsive polypeptide nanogel for chemotherapy and enhanced immunotherapy against cervical cancer
Immunotherapy is a cornerstone in cancer treatment, celebrated for its precision, ability to eliminate residual cancer cells, and potential to avert tumor recurrence. Nonetheless, its effectiveness is frequently undermined by the immunosuppressive milieu created by tumors. This study presents a nove...
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Elsevier
2025-02-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006424004733 |
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| author | Zhimin Bai Yibo Yang Zutong Cui Wenming Liang Xin Zhang Zihan Zhang Jianming Sun Zhiwei Liu Kun Li Ming Shi Jian Li |
| author_facet | Zhimin Bai Yibo Yang Zutong Cui Wenming Liang Xin Zhang Zihan Zhang Jianming Sun Zhiwei Liu Kun Li Ming Shi Jian Li |
| author_sort | Zhimin Bai |
| collection | DOAJ |
| description | Immunotherapy is a cornerstone in cancer treatment, celebrated for its precision, ability to eliminate residual cancer cells, and potential to avert tumor recurrence. Nonetheless, its effectiveness is frequently undermined by the immunosuppressive milieu created by tumors. This study presents a novel nanogel-based drug delivery system, DOX-4PI@CpG@Lipo@Gel (DPCLG), engineered to respond to Matrix Metallopeptidase-2 (MMP-2)—a protease abundant in the tumor microenvironment (TME). This system enables the controlled release of two distinct types of liposomes within the TME. The first, DOX-4PI@Liposome (DPL), carries doxorubicin (DOX) and 4-phenylimidazole (4PI), targeting cancer cells to provide chemotherapeutic effects while diminishing the immunosuppressive environment. The second, a mannosyl-modified cationic liposome (CL), is loaded with Cytosine phosphate guanine (CpG) oligodeoxynucleotides to specifically target M2 phenotype macrophages, reversing their tumor-associated phenotype (TAM) and activating immune cytokines to promote tumor destruction. Our findings indicate that DPCLG significantly curtails tumor growth, both in vitro and in vivo, mitigates the immunosuppressive TME, and triggers a potent systemic immune response. This study underscores the potential of DPCLG as an advanced, dual-targeting drug delivery system for comprehensive cancer therapy. |
| format | Article |
| id | doaj-art-371c0fb78c7d4456a7f63c4ed2c53cfd |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-371c0fb78c7d4456a7f63c4ed2c53cfd2025-01-17T04:52:08ZengElsevierMaterials Today Bio2590-00642025-02-0130101412Double-targeted liposomes coated with matrix metallopeptidase-2-responsive polypeptide nanogel for chemotherapy and enhanced immunotherapy against cervical cancerZhimin Bai0Yibo Yang1Zutong Cui2Wenming Liang3Xin Zhang4Zihan Zhang5Jianming Sun6Zhiwei Liu7Kun Li8Ming Shi9Jian Li10Hebei Key Laboratory of Applied Chemistry, Hebei Key Laboratory of Nanobiotechnology, Hebei Key Laboratory of Heavy Metal Deep-Remediation in Water and Resource Reuse, Yanshan University, Qinhuangdao, 066004, ChinaHebei Key Laboratory of Applied Chemistry, Hebei Key Laboratory of Nanobiotechnology, Hebei Key Laboratory of Heavy Metal Deep-Remediation in Water and Resource Reuse, Yanshan University, Qinhuangdao, 066004, ChinaHebei Key Laboratory of Applied Chemistry, Hebei Key Laboratory of Nanobiotechnology, Hebei Key Laboratory of Heavy Metal Deep-Remediation in Water and Resource Reuse, Yanshan University, Qinhuangdao, 066004, ChinaHebei Key Laboratory of Applied Chemistry, Hebei Key Laboratory of Nanobiotechnology, Hebei Key Laboratory of Heavy Metal Deep-Remediation in Water and Resource Reuse, Yanshan University, Qinhuangdao, 066004, ChinaHebei Key Laboratory of Applied Chemistry, Hebei Key Laboratory of Nanobiotechnology, Hebei Key Laboratory of Heavy Metal Deep-Remediation in Water and Resource Reuse, Yanshan University, Qinhuangdao, 066004, ChinaHebei Key Laboratory of Applied Chemistry, Hebei Key Laboratory of Nanobiotechnology, Hebei Key Laboratory of Heavy Metal Deep-Remediation in Water and Resource Reuse, Yanshan University, Qinhuangdao, 066004, ChinaHebei Key Laboratory of Applied Chemistry, Hebei Key Laboratory of Nanobiotechnology, Hebei Key Laboratory of Heavy Metal Deep-Remediation in Water and Resource Reuse, Yanshan University, Qinhuangdao, 066004, ChinaHebei Key Laboratory of Applied Chemistry, Hebei Key Laboratory of Nanobiotechnology, Hebei Key Laboratory of Heavy Metal Deep-Remediation in Water and Resource Reuse, Yanshan University, Qinhuangdao, 066004, ChinaHebei Key Laboratory of Applied Chemistry, Hebei Key Laboratory of Nanobiotechnology, Hebei Key Laboratory of Heavy Metal Deep-Remediation in Water and Resource Reuse, Yanshan University, Qinhuangdao, 066004, ChinaHebei Key Laboratory of Applied Chemistry, Hebei Key Laboratory of Nanobiotechnology, Hebei Key Laboratory of Heavy Metal Deep-Remediation in Water and Resource Reuse, Yanshan University, Qinhuangdao, 066004, ChinaCorresponding author.; Hebei Key Laboratory of Applied Chemistry, Hebei Key Laboratory of Nanobiotechnology, Hebei Key Laboratory of Heavy Metal Deep-Remediation in Water and Resource Reuse, Yanshan University, Qinhuangdao, 066004, ChinaImmunotherapy is a cornerstone in cancer treatment, celebrated for its precision, ability to eliminate residual cancer cells, and potential to avert tumor recurrence. Nonetheless, its effectiveness is frequently undermined by the immunosuppressive milieu created by tumors. This study presents a novel nanogel-based drug delivery system, DOX-4PI@CpG@Lipo@Gel (DPCLG), engineered to respond to Matrix Metallopeptidase-2 (MMP-2)—a protease abundant in the tumor microenvironment (TME). This system enables the controlled release of two distinct types of liposomes within the TME. The first, DOX-4PI@Liposome (DPL), carries doxorubicin (DOX) and 4-phenylimidazole (4PI), targeting cancer cells to provide chemotherapeutic effects while diminishing the immunosuppressive environment. The second, a mannosyl-modified cationic liposome (CL), is loaded with Cytosine phosphate guanine (CpG) oligodeoxynucleotides to specifically target M2 phenotype macrophages, reversing their tumor-associated phenotype (TAM) and activating immune cytokines to promote tumor destruction. Our findings indicate that DPCLG significantly curtails tumor growth, both in vitro and in vivo, mitigates the immunosuppressive TME, and triggers a potent systemic immune response. This study underscores the potential of DPCLG as an advanced, dual-targeting drug delivery system for comprehensive cancer therapy.http://www.sciencedirect.com/science/article/pii/S2590006424004733A nanogel-based drug delivery system4-PhenylimidazoleMatrix Metallopeptidase-2Immunosuppressive tumor environmentImmunotherapy |
| spellingShingle | Zhimin Bai Yibo Yang Zutong Cui Wenming Liang Xin Zhang Zihan Zhang Jianming Sun Zhiwei Liu Kun Li Ming Shi Jian Li Double-targeted liposomes coated with matrix metallopeptidase-2-responsive polypeptide nanogel for chemotherapy and enhanced immunotherapy against cervical cancer Materials Today Bio A nanogel-based drug delivery system 4-Phenylimidazole Matrix Metallopeptidase-2 Immunosuppressive tumor environment Immunotherapy |
| title | Double-targeted liposomes coated with matrix metallopeptidase-2-responsive polypeptide nanogel for chemotherapy and enhanced immunotherapy against cervical cancer |
| title_full | Double-targeted liposomes coated with matrix metallopeptidase-2-responsive polypeptide nanogel for chemotherapy and enhanced immunotherapy against cervical cancer |
| title_fullStr | Double-targeted liposomes coated with matrix metallopeptidase-2-responsive polypeptide nanogel for chemotherapy and enhanced immunotherapy against cervical cancer |
| title_full_unstemmed | Double-targeted liposomes coated with matrix metallopeptidase-2-responsive polypeptide nanogel for chemotherapy and enhanced immunotherapy against cervical cancer |
| title_short | Double-targeted liposomes coated with matrix metallopeptidase-2-responsive polypeptide nanogel for chemotherapy and enhanced immunotherapy against cervical cancer |
| title_sort | double targeted liposomes coated with matrix metallopeptidase 2 responsive polypeptide nanogel for chemotherapy and enhanced immunotherapy against cervical cancer |
| topic | A nanogel-based drug delivery system 4-Phenylimidazole Matrix Metallopeptidase-2 Immunosuppressive tumor environment Immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2590006424004733 |
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