ArticleJournal of controlled release : official journal of the Controlled Release Society2015
Polypeptide-based nanogels co-encapsulating a synergistic combination of doxorubicin with 17-AAG show potent anti-tumor activity in ErbB2-driven breast cancer models.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Impact of nanoparticles on amyloid β-induced Alzheimer's disease, tuberculosis, leprosy and cancer: a systematic review.Bioscience reports · 2023Pooled it
- Perfluoroether Peptide-Modified Artificial Viral Capsid for Enhanced Doxorubicin Delivery to Liver Cancer Cells.ACS omega · 2026Article
- Review
- Polypeptide-Based Systems: From Synthesis to Application in Drug Delivery.Pharmaceutics · 2023Review
- Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval.Advanced drug delivery reviews · 2020Review
- Tuning polypeptide-based micellar carrier for efficient combination therapy of ErbB2-positive breast cancer.Journal of controlled release : official journal of the Controlled Release Society · 2017Article
- Hypoxia inducible factor down-regulation, cancer and cancer stem cells (CSCs): ongoing success stories.MedChemComm · 2017Review
- Nanogels: An overview of properties, biomedical applications and obstacles to clinical translation.Journal of controlled release : official journal of the Controlled Release Society · 2016Review
- Targeted delivery of platinum-taxane combination therapy in ovarian cancer.Journal of controlled release : official journal of the Controlled Release Society · 2015Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
Abstract
ErbB2-driven breast cancers constitute 20-25% of the cases diagnosed within the USA. The humanized anti-ErbB2 monoclonal antibody, Trastuzumab (Herceptin™; Genentech), with chemotherapy is the current standard of treatment. Novel agents and strategies continue to be explored, given the challenges posed by Trastuzumab-resistance development in most patients. The HSP90 inhibitor, 17-allylaminodemethoxygeldanamycin (17-AAG), which induces ErbB2 degradation and attenuates downstream oncogenic signaling, is one such agent that showed significant promise in early phase I and II clinical trials. Its low water solubility, potential toxicities and undesirable side effects observed in patients, partly due to the Cremophor-based formulation, have been discouraging factors in the advancement of this promising drug into clinical use. Encapsulation of 17-AAG into polymeric nanoparticle formulations, particularly in synergistic combination with conventional chemotherapeutics, represents an alternative approach to overcome these problems. Herein, we report an efficient co-encapsulation of 17-AAG and doxorubicin, a clinically well-established and effective modality in breast cancer treatment, into biodegradable and biocompatible polypeptide-based nanogels. Dual drug-loaded nanogels displayed potent cytotoxicity in a breast cancer cell panel and exerted selective synergistic anticancer activity against ErbB2-overexpressing breast cancer cell lines. Analysis of ErbB2 degradation confirmed efficient 17-AAG release from nanogels with activity comparable to free 17-AAG. Furthermore, nanogels containing both 17-AAG and doxorubicin exhibited superior antitumor efficacy in vivo in an ErbB2-driven xenograft model compared to the combination of free drugs. These studies demonstrate that polypeptide-based nanogels can serve as novel nanocarriers for encapsulating 17-AAG along with other chemotherapeutics, providing an opportunity to overcome solubility issues and thereby exploit its full potential as an anti-cancer agent.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.