Engineered ultrasmall nanoparticle drug-immune conjugates with “hit and run” tumor delivery to eradicate gastric cancer Journal Article
| Authors: | Zhang, L.; Aragon-Sanabria, V.; Aditya, A.; Marelli, M.; Cao, T.; Chen, F.; Yoo, B.; Ma, K.; Zhuang, L.; Cailleau, T.; Masterson, L.; Turker, M. Z.; Lee, R.; DeLeon, G.; Monette, S.; Colombo, R.; Christie, R. J.; Zanzonico, P.; Wiesner, U.; Subramony, J. A.; Bradbury, M. S. |
| Article Title: | Engineered ultrasmall nanoparticle drug-immune conjugates with “hit and run” tumor delivery to eradicate gastric cancer |
| Abstract: | Despite advances by recently approved antibody-drug conjugates in treating advanced gastric cancer patients, substantial limitations remain. Here, several key obstacles are overcome by developing a first-in-class ultrasmall (sub-8-nanometer (nm)) anti-human epidermal growth factor receptor 2 (HER2)-targeting drug-immune conjugate nanoparticle therapy. This multivalent fluorescent core–shell silica nanoparticle bears multiple anti-HER2 single-chain variable fragments (scFv), topoisomerase inhibitors, and deferoxamine moieties. Most surprisingly, drawing upon its favorable physicochemical, pharmacokinetic, clearance, and target-specific dual-modality imaging properties in a “hit and run” approach, this conjugate eradicated HER2-expressing gastric tumors without any evidence of tumor regrowth, while exhibiting a wide therapeutic index. Therapeutic response mechanisms are accompanied by the activation of functional markers, as well as pathway-specific inhibition. Results highlight the potential clinical utility of this molecularly engineered particle drug-immune conjugate and underscore the versatility of the base platform as a carrier for conjugating an array of other immune products and payloads. © 2022 The Authors. Advanced Therapeutics published by Wiley-VCH GmbH. |
| Keywords: | silica; therapy; gastric cancer; topoisomerase inhibitor; her2 targeted; ultrasmall; nanoparticle drug-immune conjugate |
| Journal Title: | Advanced Therapeutics |
| Volume: | 6 |
| Issue: | 3 |
| ISSN: | 2366-3987 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2023-03-01 |
| Start Page: | 2200209 |
| Language: | English |
| DOI: | 10.1002/adtp.202200209 |
| PROVIDER: | scopus |
| PMCID: | PMC10061546 |
| PUBMED: | 37007587 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Michelle S. Bradbury -- Source: Scopus |
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