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Bio-orthogonal click chemistry strategy for PD-L1-targeted imaging and pyroptosis-mediated chemo-immunotherapy of triple-negative breast cancer.
- Source :
-
Journal of nanobiotechnology [J Nanobiotechnology] 2024 Aug 01; Vol. 22 (1), pp. 461. Date of Electronic Publication: 2024 Aug 01. - Publication Year :
- 2024
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Abstract
- Background: The combination of programmed cell death ligand-1 (PD-L1) immune checkpoint blockade (ICB) and immunogenic cell death (ICD)-inducing chemotherapy has shown promise in cancer immunotherapy. However, triple-negative breast cancer (TNBC) patients undergoing this treatment often face obstacles such as systemic toxicity and low response rates, primarily attributed to the immunosuppressive tumor microenvironment (TME).<br />Methods and Results: In this study, PD-L1-targeted theranostic systems were developed utilizing anti-PD-L1 peptide (APP) conjugated with a bio-orthogonal click chemistry group. Initially, TNBC was treated with azide-modified sugar to introduce azide groups onto tumor cell surfaces through metabolic glycoengineering. A PD-L1-targeted probe was developed to evaluate the PD-L1 status of TNBC using magnetic resonance/near-infrared fluorescence imaging. Subsequently, an acidic pH-responsive prodrug was employed to enhance tumor accumulation via bio-orthogonal click chemistry, which enhances PD-L1-targeted ICB, the pH-responsive DOX release and induction of pyroptosis-mediated ICD of TNBC. Combined PD-L1-targeted chemo-immunotherapy effectively reversed the immune-tolerant TME and elicited robust tumor-specific immune responses, resulting in significant inhibition of tumor progression.<br />Conclusions: Our study has successfully engineered a bio-orthogonal multifunctional theranostic system, which employs bio-orthogonal click chemistry in conjunction with a PD-L1 targeting strategy. This innovative approach has been demonstrated to exhibit significant promise for both the targeted imaging and therapeutic intervention of TNBC.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Female
Mice
Humans
Cell Line, Tumor
Tumor Microenvironment drug effects
Mice, Inbred BALB C
Doxorubicin pharmacology
Doxorubicin chemistry
Doxorubicin therapeutic use
Optical Imaging methods
Prodrugs chemistry
Prodrugs pharmacology
Triple Negative Breast Neoplasms drug therapy
Click Chemistry
B7-H1 Antigen metabolism
Immunotherapy methods
Pyroptosis drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1477-3155
- Volume :
- 22
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of nanobiotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 39090622
- Full Text :
- https://doi.org/10.1186/s12951-024-02727-7