期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 17, 期 -, 页码 5747-5760出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S381628
关键词
functionalized nanomaterial; natural ligand; nanoparticle targeting; squamous carcinoma; globotriaosylceramide
资金
- ISCIII [PI19/00349, DTS19/00033]
- European Regional Development Fund
- COST action Nano2Clinic [CA17140]
- IDIVAL [PREVAL16/02, INNVAL20/13, INNVAL21/ 19]
- European Research Council [ERC AdG 787510, 4DbioSERS]
- Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency [MDM-20170720]
- panish Ministerio de Ciencia, Innovacion y Universidades [PGC2018101464-B-I00]
- HIPERNANO [RED2018-102626-T]
- ISCIII/FIS-FEDER [PI20/00880]
- Asociacion Espanola Contra el Cancer (AECC
- Spain) [PRDCA19003GALA]
In this study, a high-affinity protein-ligand was designed using Shiga toxin to target specific receptors in head and neck tumors. Functionalized gold nanorods were able to selectively kill targeted cancer cells after laser radiation. This research demonstrates the potential of using natural ligands to guide nanomedicines for the treatment of aggressive localized cancers.
Introduction: A great challenge in nanomedicine, and more specifically in theranostics, is to improve the specificity, selectivity, and targeting of nanomaterials towards target tissues or cells. The topical use of nanomedicines as adjuvants to systemic chemotherapy can significantly improve the survival of patients affected by localized carcinomas, reducing the side effects of traditional drugs and preventing local recurrences. Methods: Here, we have used the Shiga toxin, to design a safe, high-affinity protein-ligand (ShTxB) to bind the globotriaosylcer-amide receptor (GB3) that is overexpressed on the surfaces of preneoplastic and malignant cancer cells in the head and neck tumors. Results: We find that ShTxB functionalized gold nanorods are efficiently retrotranslocated to the GB3-positive cell cytoplasms. After 3 minutes of laser radiation with a wavelength resonant with the AuNR longitudinal localized surface plasmon, the death of the targeted cancer cells is activated. Both preclinical murine models and patient biopsy cells show the non-cytotoxic nature of these functionalized nanoparticles before light activation and their treatment selectivity. Discussion: These results show how the use of nanomedicines directed by natural ligands can represent an effective treatment for aggressive localized cancers, such as squamous cell carcinoma of the oral cavity.
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