PD-L1 targeted antibody-polymer-Epirubicin conjugate prolongs survival in a preclinical murine model of advanced ovarian cancer DOI Creative Commons
Jiahui Li, Hasan Al Faruque,

Shannuo Li

и другие.

Journal of Controlled Release, Год журнала: 2025, Номер unknown, С. 113682 - 113682

Опубликована: Апрель 1, 2025

Following successful design of polymer enhanced rituximab-epirubicin (EPI) conjugates targeted to non-Hodgkin lymphoma (Zhang et al. 2017), we developed U6244-051 that consists anti-PD-L1 antibody (αPD-L1) and semitelechelic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-epirubicin (ST-P-EPI); the latter is attached αPD-L1 via Cu-free azide/alkyne cycloaddition. This new polymer-enhanced antibody-drug conjugate (pADC) not only exhibits a high drug-to-antibody ratio (DAR ~ 30-40) but also integrates immune checkpoint blockade with long-lasting immunogenic anticancer chemotherapy, providing an innovative chemo-immuno combination modality. The biological properties were evaluated using ID8-Luc murine ovarian cancer cells in vitro vivo. In vitro, treatment induced immunomodulatory changes, including upregulation calreticulin, PD-L1, MHC I, suggesting tumor cell visibility system. vivo efficacy was assessed syngeneic model (C57BL/6 J mice inoculated 5 × 106 cells/mouse). resulted 100 % survival at day 100, despite initiation advanced disease stage. Treatment modulated microenvironment by reducing immunosuppressive populations (TAMs MDSCs) enhancing T recruitment activation. A decrease PD-L1 expression increased I correlated immune-mediated clearance. Additionally, reduced Treg levels CD8+ activation contributed more effective antitumor response. Repeated dosing amplified effects, leading durable immunity. These results highlight as next-generation pADC translational potential, offering on-target, off-tumor toxicity.

Язык: Английский

Stable liposomal cerasome for ultrasound/H2O2-activated CO release to augment tumor chemotherapy and immunotherapy DOI

Suhui Sun,

Ruiqi Wu,

S. Sha

и другие.

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 161398 - 161398

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
The Application of Dendritic Cells Vaccines in Tumor Therapy and Their Combination with Biomimetic Nanoparticles DOI Creative Commons
Tong Zhu, Yuexin Li, Yutao Wang

и другие.

Vaccines, Год журнала: 2025, Номер 13(4), С. 337 - 337

Опубликована: Март 21, 2025

Dendritic cells (DCs) act as a bridge between innate and adaptive immunity by presenting antigens to effector immune have shown broad application potential in tumor immunotherapy. However, the clinical translation of DC vaccines encounters significant challenges, such immunosuppressive microenvironment (TME) sub-optimal function vaccine efficacy vivo. In this review, our investigation has uncovered latest developments their cancer immunotherapy, with special emphasis on integration nanotechnology. Several types nanomaterials, including protein cage nanoparticles (NPs), biomimetic NPs, targeted multifunctional been developed enhance antigen presentation ability DCs stimulatory effects T cells. addition, we also summarized synergistic anti-cancer checkpoint inhibitors, chemotherapy, radiotherapy. recent advances nanotechnology made it possible develop novel biomarkers that can capacity stimulate These not only improve accuracy precision design but provide new insights into understanding mechanisms DC-mediated response. Despite challenges pertaining technical complexities individual adaptation production vaccines, personalized immunotherapy based is expected become an important part treatment rapid biotechnology immunology. This review provides perspectives solutions for optimal therapy.

Язык: Английский

Процитировано

0
UiO-based platforms in biomedicine: Advanced nanovehicles for effective treatment DOI

Ren Zhang,

Abdulnasser Mahmoud Karami,

Qianying Huang

и другие.

Materials Today Chemistry, Год журнала: 2025, Номер 45, С. 102645 - 102645

Опубликована: Март 22, 2025

Язык: Английский

Процитировано

0
A Glutathione‐Responsive System with Prodrug and Sensitization Strategies for Targeted Therapy of Glioma DOI
Xifeng Zhang,

Bilan Wang,

Xin Qi

и другие.

Small, Год журнала: 2025, Номер unknown

Опубликована: Март 22, 2025

Abstract Glioblastoma represents a highly aggressive form of malignant tumor within the central nervous system. Although chemotherapy remains primary therapeutic strategy, its efficacy is often limited. To overcome limitations associated with chemotherapeutic agents, such as high toxicity and non‐specific adverse effects, novel nanoparticle system comprising cRGD‐modified glutathione (GSH)‐responsive polymers, PEG‐ss‐Dox apatinib (AP) (PDOX‐AP/cRGD‐NPs) developed. PDOX‐AP/cRGD‐NPs show effective penetration blood‐brain barrier (BBB), facilitate targeted delivery to brain tumors, exhibit controlled drug release. more effect in reducing viability GL‐261, U87‐MG, LN‐229 cells, inhibiting clonogenicity, suppressing anti‐apoptotic protein expression than PDOX/cRGD‐NPs or AP/cRGD‐NPs. Additionally, substantially increase uptake, BBB penetration, apoptosis rates, proportion cells G2 phase. In vivo experiments further reveal that cRGD‐directed nanoparticles superior accumulation glioma regions compared their non‐cRGD‐modified counterparts. interim, demonstrate significant both ectopic orthotopic growth GL‐261 gliomas, well thereby markedly extending median survival duration. This study introduces promising co‐delivery for combination chemotherapy.

Язык: Английский

Процитировано

0
PD-L1 targeted antibody-polymer-Epirubicin conjugate prolongs survival in a preclinical murine model of advanced ovarian cancer DOI Creative Commons
Jiahui Li, Hasan Al Faruque,

Shannuo Li

и другие.

Journal of Controlled Release, Год журнала: 2025, Номер unknown, С. 113682 - 113682

Опубликована: Апрель 1, 2025

Following successful design of polymer enhanced rituximab-epirubicin (EPI) conjugates targeted to non-Hodgkin lymphoma (Zhang et al. 2017), we developed U6244-051 that consists anti-PD-L1 antibody (αPD-L1) and semitelechelic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-epirubicin (ST-P-EPI); the latter is attached αPD-L1 via Cu-free azide/alkyne cycloaddition. This new polymer-enhanced antibody-drug conjugate (pADC) not only exhibits a high drug-to-antibody ratio (DAR ~ 30-40) but also integrates immune checkpoint blockade with long-lasting immunogenic anticancer chemotherapy, providing an innovative chemo-immuno combination modality. The biological properties were evaluated using ID8-Luc murine ovarian cancer cells in vitro vivo. In vitro, treatment induced immunomodulatory changes, including upregulation calreticulin, PD-L1, MHC I, suggesting tumor cell visibility system. vivo efficacy was assessed syngeneic model (C57BL/6 J mice inoculated 5 × 106 cells/mouse). resulted 100 % survival at day 100, despite initiation advanced disease stage. Treatment modulated microenvironment by reducing immunosuppressive populations (TAMs MDSCs) enhancing T recruitment activation. A decrease PD-L1 expression increased I correlated immune-mediated clearance. Additionally, reduced Treg levels CD8+ activation contributed more effective antitumor response. Repeated dosing amplified effects, leading durable immunity. These results highlight as next-generation pADC translational potential, offering on-target, off-tumor toxicity.

Язык: Английский

Процитировано

0