Academic Journal
Targeted Hyperbranched Nanoparticles for Delivery of Doxorubicin in Breast Cancer Brain Metastasis
| العنوان: | Targeted Hyperbranched Nanoparticles for Delivery of Doxorubicin in Breast Cancer Brain Metastasis |
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| المؤلفون: | Malcolm Lim, Nicholas L. Fletcher, Jodi M. Saunus, Amy E. McCart Reed, Haarika Chittoory, Peter T. Simpson, Kristofer J. Thurecht, Sunil R. Lakhani |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Biochemistry, Cell Biology, Genetics, Molecular Biology, Pharmacology, Biotechnology, Cancer, Hematology, Space Science, Biological Sciences not elsewhere classified, short physiological half, reduced tumor size, prolonged overall survival, poor brain penetration, oocyte toxicity compared, limited treatment options, high dosage required, endosomal acidic conditions, targeted hyperbranched nanoparticles, targeted hbp nanomedicine, breast cancer bm, targeted hbp, hyperbranched polymers, cancer cell, well tolerated, treat bm, therapeutic testing, target toxicities, taken together, standard chemotherapy |
| الوصف: | Breast cancer brain metastases (BM) are associated with a dismal prognosis and very limited treatment options. Standard chemotherapy is challenging in BM patients because the high dosage required for an effective outcome causes unacceptable systemic toxicities, a consequence of poor brain penetration, and a short physiological half-life. Nanomedicines have the potential to circumvent off-target toxicities and factors limiting the efficacy of conventional chemotherapy. The HER3 receptor is commonly expressed in breast cancer BM. Here, we investigate the use of hyperbranched polymers (HBP) functionalized with a HER3 bispecific-antibody fragment for cancer cell-specific targeting and pH-responsive release of doxorubicin (DOX) to selectively deliver and treat BM. We demonstrated that DOX-release from the HBP carrier was controlled, gradual, and greater in endosomal acidic conditions (pH 5.5) relative to physiologic pH (pH 7.4). We showed that the HER3-targeted HBP with DOX payload was HER3-specific and induced cytotoxicity in BT474 breast cancer cells (IC 50 : 17.6 μg/mL). Therapeutic testing in a BM mouse model showed that HER3-targeted HBP with DOX payload impacted tumor proliferation, reduced tumor size, and prolonged overall survival. HER3-targeted HBP level detected in ex vivo brain samples was 14-fold more than untargeted-HBP. The HBP treatments were well tolerated, with less cardiac and oocyte toxicity compared to free DOX. Taken together, our HER3-targeted HBP nanomedicine has the potential to deliver chemotherapy to BM while reducing chemotherapy-associated toxicities. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | https://figshare.com/articles/journal_contribution/Targeted_Hyperbranched_Nanoparticles_for_Delivery_of_Doxorubicin_in_Breast_Cancer_Brain_Metastasis/24573571 |
| DOI: | 10.1021/acs.molpharmaceut.3c00558.s001 |
| الاتاحة: | https://doi.org/10.1021/acs.molpharmaceut.3c00558.s001 https://figshare.com/articles/journal_contribution/Targeted_Hyperbranched_Nanoparticles_for_Delivery_of_Doxorubicin_in_Breast_Cancer_Brain_Metastasis/24573571 |
| Rights: | CC BY-NC 4.0 |
| رقم الانضمام: | edsbas.B25F0303 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.molpharmaceut.3c00558.s001 |
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