Your browser doesn't support javascript.
loading
Lactoferrin-dual drug nanoconjugate: Synergistic anti-tumor efficacy of docetaxel and the NF-κB inhibitor celastrol.
Abdelmoneem, Mona A; Abd Elwakil, Mahmoud M; Khattab, Sherine N; Helmy, Maged W; Bekhit, Adnan A; Abdulkader, Mohammad A; Zaky, Amira; Teleb, Mohamed; Elkhodairy, Kadria A; Albericio, Fernando; Elzoghby, Ahmed O.
Afiliação
  • Abdelmoneem MA; Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; Department of Pharmaceutics, Faculty of Pharmacy, Damanhur University, Damanhur, Egypt; Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard
  • Abd Elwakil MM; Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; Graduate school of Pharmaceutical Sciences, Hokkaido University, Japan.
  • Khattab SN; Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; Department of Chemistry, Faculty of Science, Alexandria University, Alexandria 21321, Egypt. Electronic address: sh.n.khattab@gmail.com.
  • Helmy MW; Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Damanhur University, Damanhur, Egypt.
  • Bekhit AA; Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; Pharmacy Program, Allied Health Department, College of Health and Sport Sciences, Un
  • Abdulkader MA; Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria 21511, Egypt.
  • Zaky A; Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria 21511, Egypt.
  • Teleb M; Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
  • Elkhodairy KA; Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
  • Albericio F; School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4001, South Africa; CIBER-BBN, Networking Centre on Bioengineering Biomaterials and Nanomedicine, Barcelona Science Park, Barcelona 08028, Spain; Department of Organic Chemistry, University of Barcelona, Barcelona 08028, Spain.
  • Elzoghby AO; Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Harvard-MIT Division of Health Sciences & Tec
Mater Sci Eng C Mater Biol Appl ; 118: 111422, 2021 Jan.
Article em En | MEDLINE | ID: mdl-33255023
Despite the progress in cancer nanotherapeutics, some obstacles still impede the success of nanocarriers and hinder their clinical translation. Low drug loading, premature drug release, off-target toxicity and multi-drug resistance are among the most difficult challenges. Lactoferrin (LF) has demonstrated a great tumor targeting capacity via its high binding affinity to low density lipoprotein (LDL) and transferrin (Tf) receptors overexpressed by various cancer cells. Herein, docetaxel (DTX) and celastrol (CST) could be successfully conjugated to LF backbone for synergistic breast cancer therapy. Most importantly, the conjugate self-assembled forming nanoparticles of 157.8 nm with elevated loading for both drugs (6.94 and 5.98% for DTX and CST, respectively) without risk of nanocarrier instability. Moreover, the nanoconjugate demonstrated enhanced in vivo anti-tumor efficacy in breast cancer-bearing mice, as reflected by a reduction in tumor volume, prolonged survival rate and significant suppression of NF-κB p65, TNF-α, COX-2 and Ki-67 expression levels compared to the group given free combined DTX/CST therapy and to positive control. This study demonstrated the proof-of-principle for dual drug coupling to LF as a versatile nanoplatform that could augment their synergistic anticancer efficacy.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Nanopartículas / Antineoplásicos Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Nanopartículas / Antineoplásicos Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article