دورية أكاديمية
Breaking the selectivity-uptake trade-off of photoimmunoconjugates with nanoliposomal irinotecan for synergistic multi-tier cancer targeting
| العنوان: | Breaking the selectivity-uptake trade-off of photoimmunoconjugates with nanoliposomal irinotecan for synergistic multi-tier cancer targeting |
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| المؤلفون: | Liang, B.J., Pigula, M., Huang, H.-C. |
| بيانات النشر: | BioMed Central Ltd. |
| سنة النشر: | 2020 |
| المجموعة: | UMB Digital Archive (University of Maryland, Baltimore) |
| مصطلحات موضوعية: | Benzoporphyrin derivative, Epidermal growth factor receptor, Irinotecan liposome injection, Multi-drug delivery, Photoimmunoconjugate |
| الوصف: | Background: Photoimmunotherapy involves targeted delivery of photosensitizers via an antibody conjugate (i.e., photoimmunoconjugate, PIC) followed by light activation for selective tumor killing. The trade-off between PIC selectivity and PIC uptake is a major drawback limiting the efficacy of photoimmunotherapy. Despite ample evidence showing that photoimmunotherapy is most effective when combined with chemotherapy, the design of nanocarriers to co-deliver PICs and chemotherapy drugs remains an unmet need. To overcome these challenges, we developed a novel photoimmunoconjugate-nanoliposome (PIC-Nal) comprising of three clinically used agents: anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody cetuximab (Cet), benzoporphyrin derivative (BPD) photosensitizer, and irinotecan (IRI) chemotherapy. Results: The BPD photosensitizers were first tethered to Cet at a molar ratio of 6:1 using carbodiimide chemistry to form PICs. Conjugation of PICs onto nanoliposome irinotecan (Nal–IRI) was facilitated by copper-free click chemistry, which resulted in monodispersed PIC–Nal–IRI with an average size of 158.8 ± 15.6 nm. PIC–Nal–IRI is highly selective against EGFR-overexpressing epithelial ovarian cancer cells with 2- to 6-fold less accumulation in low EGFR expressing cells. Successful coupling of PIC onto Nal–IRI enhanced PIC uptake and photoimmunotherapy efficacy by up to 30% in OVCAR-5 cells. Furthermore, PIC–Nal–IRI synergistically reduced cancer viability via a unique three-way mechanism (i.e., EGFR downregulation, mitochondrial depolarization, and DNA damage). Conclusion: It is increasingly evident that the most effective therapies for cancer will involve combination treatments that target multiple non-overlapping pathways while minimizing side effects. Nanotechnology combined with photochemistry provides a unique opportunity to simultaneously deliver and activate multiple drugs that target all major regions of a cancer cell—plasma membrane, cytoplasm, and nucleus. PIC–Nal–IRI offers a promising ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | Journal of Nanobiotechnology; https://www.scopus.com/inward/record.uri?eid=2-s2.0-85077377648&doi=10.1186%2fs12951-019-0560-5&partnerID=40&md5=6bdcb944fca58df1c11a067fcb070662Test; http://hdl.handle.net/10713/11627Test |
| DOI: | 10.1186/s12951-019-0560-5 |
| الإتاحة: | https://doi.org/10.1186/s12951-019-0560-5Test http://hdl.handle.net/10713/11627Test |
| رقم الانضمام: | edsbas.5E97DBD3 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12951-019-0560-5 |
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