4 results on '"Ferreira, Carolina A."'
Search Results
2. Targeting angiogenesis for radioimmunotherapy with a Lu-labeled antibody.
- Author
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Ehlerding, Emily B., Lacognata, Saige, Dawei Jiang, Ferreira, Carolina A., Goel, Shreya, Hernandez, Reinier, Jeffery, Justin J., Theuer, Charles P., and Weibo Cai
- Subjects
NEOVASCULARIZATION ,RADIOIMMUNOTHERAPY ,TUMOR growth ,METASTASIS ,ENDOGLIN ,RADIOLABELING - Abstract
Purpose: Increased angiogenesis is a marker of aggressiveness in many cancers. Targeted radionuclide therapy of these cancers with angiogenesis-targeting agents may curtail this increased blood vessel formation and slow the growth of tumors, both primary and metastatic. CD105, or endoglin, has a primary role in angiogenesis in a number of cancers, making this a widely applicable target for targeted radioimmunotherapy. Methods: The anti-CD105 antibody, TRC105 (TRACON Pharmaceuticals), was conjugated with DTPA for radiolabeling with Lu ( t 6.65 days). Balb/c mice were implanted with 4T1 mammary carcinoma cells, and five study groups were used: Lu only, TRC105 only, Lu-DTPA-IgG (a nonspecific antibody), Lu-DTPA-TRC105 low-dose, and Lu-DTPA-TRC105 high-dose. Toxicity of the agent was monitored by body weight measurements and analysis of blood markers. Biodistribution studies of Lu-DTPA-TRC105 were also performed at 1 and 7 days after injection. Ex vivo histology studies of various tissues were conducted at 1, 7, and 30 days after injection of high-dose Lu-DTPA-TRC105. Results: Biodistribution studies indicated steady uptake of Lu-DTPA-TRC105 in 4T1 tumors between 1 and 7 days after injection (14.3 ± 2.3%ID/g and 11.6 ± 6.1%ID/g, respectively; n = 3) and gradual clearance from other organs. Significant inhibition of tumor growth was observed in the high-dose group, with a corresponding significant increase in survival ( p < 0.001, all groups). In most study groups (all except the nonspecific IgG group), the body weights of the mice did not decrease by more than 10%, indicating the safety of the injected agents. Serum alanine transaminase levels remained nearly constant indicating no damage to the liver (a primary clearance organ of the agent), and this was confirmed by ex vivo histological analyses. Conclusion: Lu-DTPA-TRC105, when administered at a sufficient dose, is able to curtail tumor growth and provide a significant survival benefit without off-target toxicity. Thus, this targeted agent could be used in combination with other treatment options to slow tumor growth allowing the other agents to be more effective. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
3. Evaluation of linear versus star-like polymer anti-cancer nanomedicines in mouse models.
- Author
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Kostka, Libor, Kotrchová, Lenka, Randárová, Eva, Ferreira, Carolina A., Malátová, Iva, Lee, Hye Jin, Olson, Aeli P., Engle, Jonathan W., Kovář, Marek, Cai, Weibo, Šírová, Milada, and Etrych, Tomáš
- Subjects
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POSITRON emission tomography , *LABORATORY mice , *OPTICAL tomography , *HEMATOLOGIC malignancies , *DRUG carriers , *BREAST , *POLYMERS - Abstract
Nanomedicines are considered next generation therapeutics with advanced therapeutic properties and reduced side effects. Herein, we introduce tailored linear and star-like water-soluble nanosystems as stimuli-sensitive nanomedicines for the treatment of solid tumors or hematological malignancies. The polymer carrier and drug pharmacokinetics were independently evaluated to elucidate the relationship between the nanosystem structure and its distribution in the body. Positron emission tomography and optical imaging demonstrated enhanced tumor accumulation of the polymer carriers in 4T1-bearing mice with increased tumor-to-blood and tumor-to-muscle ratios. Additionally, there was a significant accumulation of doxorubicin bound to various polymer carriers in EL4 tumors, as well as excellent in vivo therapeutic activity in EL4 lymphoma and moderate efficacy in 4T1 breast carcinoma. The linear nanomedicine showed at least comparable pharmacologic properties to the star-like nanomedicines regarding doxorubicin transport. Therefore, if multiple parameters are considered such as its optimized structure and simple and reproducible synthesis, this polymer carrier system is the most promising for further preclinical and clinical investigations. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
4. HPMA-based star polymer biomaterials with tuneable structure and biodegradability tailored for advanced drug delivery to solid tumours.
- Author
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Kostka, Libor, Kotrchová, Lenka, Šubr, Vladimír, Libánská, Alena, Ferreira, Carolina A., Malátová, Iva, Lee, Hye Jin, Barnhart, Todd E., Engle, Jonathan W., Cai, Weibo, Šírová, Milada, and Etrych, Tomáš
- Subjects
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STAR-branched polymers , *MOLECULAR weights , *ACRYLAMIDE , *BIOMATERIALS , *PROPIONIC acid , *TUMORS , *COPOLYMERS - Abstract
Design, controlled synthesis, physico-chemical and biological characteristics of novel well-defined biodegradable star-shaped copolymers intended for advanced drug delivery is described. These new biocompatible star copolymers were synthesised by grafting monodispersed semitelechelic linear (sL) N -(2-hydroxypropyl)methacrylamide copolymers onto a 2,2-bis(hydroxymethyl)propionic acid (bisMPA)-based polyester dendritic core of various structures. The hydrodynamic diameter of the star copolymer biomaterials can be tuned from 13 to 31 nm and could be adjusted to a given purpose by proper selection of the bisMPA dendritic core type and generation and by considering the sL copolymer molecular weight and polymer-to-core molar ratio. The hydrolytic degradation was proved for both the star copolymers containing either dendron or dendrimer core, showing the spontaneous hydrolysis in duration of few weeks. Finally, it was shown that the therapy with the biodegradable star conjugate with attached doxorubicin strongly suppresses the tumour growth in mice and is fully curative in most of the treated animals at dose corresponding approximately to one fourth of maximum tolerated dose (MTD) value. Both new biodegradable systems show superior efficacy and tumour accumulation over the first generation of star copolymers containing non-degradable PAMAM core. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
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