Combining hydrophilic chemotherapy and hydrophobic phytotherapy via tumor-targeted albumin-QDs nano-hybrids: covalent coupling and phospholipid complexation approaches

The rationale of this study is to combine the merits of both albumin nanoparticles and quantum dots (QDs) in improved drug tumor accumulation and strong fluorescence imaging capability into one carrier. However, premature drug release from protein nanoparticles and high toxicity of QDs due to heavy...

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Veröffentlicht in:Journal of nanobiotechnology 2019-01, Vol.17 (1), p.7-19, Article 7
Hauptverfasser: Zayed, Dina G, Ebrahim, Shaker M, Helmy, Maged W, Khattab, Sherine N, Bahey-El-Din, Mohammed, Fang, Jia-You, Elkhodairy, Kadria A, Elzoghby, Ahmed O
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Sprache:eng
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Zusammenfassung:The rationale of this study is to combine the merits of both albumin nanoparticles and quantum dots (QDs) in improved drug tumor accumulation and strong fluorescence imaging capability into one carrier. However, premature drug release from protein nanoparticles and high toxicity of QDs due to heavy metal leakage are among challenging hurdles. Following this platform, we developed cancer nano-theranostics by coupling biocompatible albumin backbone to CdTe QDs and mannose moieties to enhance tumor targeting and reduce QDs toxicity. The chemotherapeutic water soluble drug pemetrexed (PMT) was conjugated via tumor-cleavable bond to the albumin backbone for tumor site-specific release. In combination, the herbal hydrophobic drug resveratrol (RSV) was preformulated as phospholipid complex which enabled its physical encapsulation into albumin nanoparticles. Albumin-QDs theranostics showed enhanced cytotoxicity and internalization into breast cancer cells that could be traced by virtue of their high fluorescence quantum yield and excellent imaging capacity. In vivo, the nanocarriers demonstrated superior anti-tumor effects including reduced tumor volume, increased apoptosis, and inhibited angiogenesis in addition to non-immunogenic response. Moreover, in vivo bioimaging test demonstrated excellent tumor-specific accumulation of targeted nanocarriers via QDs-mediated fluorescence. Mannose-grafted strategy and QD-fluorescence capability were beneficial to deliver albumin nanocarriers to tumor tissues and then to release the anticancer drugs for killing cancer cells as well as enabling tumor imaging facility. Overall, we believe albumin-QDs nanoplatform could be a potential nano-theranostic for bioimaging and targeted breast cancer therapy.
ISSN:1477-3155
1477-3155
DOI:10.1186/s12951-019-0445-7