Journal
MATERIALS SCIENCE AND ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
Volume 118, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.msec.2020.111422
Keywords
Lactoferrin; Dual drug-protein conjugate; High drug loading; Self-assembling nanoparticles; Tumor targeting; Synergistic therapy
Categories
Funding
- Science and Technology Development Fund (STDF), Ministry of Scientific Research, Egypt [15053]
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Despite progress in cancer nanotherapeutics, obstacles like low drug loading and off-target toxicity hinder the clinical success of nanocarriers. The conjugation of docetaxel and celastrol to lactoferrin shows enhanced anti-tumor efficacy in breast cancer-bearing mice, indicating potential for synergistic therapy. This study demonstrates the proof-of-principle for coupling dual drugs to lactoferrin as a versatile nanoplatform to augment their anticancer efficacy.
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 over-expressed 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-kappa B p65, TNF-alpha, 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.
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