Design and Fabrication of Multifunctional Sericin Nanoparticles for Tumor Targeting and pH-Responsive Subcellular Delivery of Cancer Chemotherapy Drugs
- 22 February 2016
- journal article
- Published by American Chemical Society (ACS) in ACS Applied Materials & Interfaces
- Vol. 8 (10), 6577-6585
- https://doi.org/10.1021/acsami.5b11617
Abstract
The severe cytotoxicity of cancer chemotherapy drugs limits their clinical applications. Various protein-based nanoparticles with good biocompatibility have been developed for chemotherapy drug delivery in hope of reducing drugs' side effects. Sericin, a natural protein from silk, has no immunogenicity and possesses diverse bioactivities that have prompted sericin's application studies. However, the potential of sericin as a multifunctional nanoscale vehicle for cancer therapy have not been fully explored. Here we report the successful fabrication and characterization of folate-conjugated sericin nanoparticles with cancer-targeting capability for pH-responsive release of doxorubicin (these nanoparticles are termed "FA-SND"). DOX is covalently linked to sericin through pH-sensitive hydrazone bonds that render a pH-triggered release property. The hydrophobicity of DOX and the hydrophilicity of sericin promote the self-assembly of sericin-DOX (SND) nanoconjugates. Folate (FA) is then covalently grafted to SND nanoconjugates as a binding unit for actively targeting cancer cells that overexpress folate receptors. Our characterization study shows that FA-SND nanoparticles exhibit negative surface charges that would reduce nonspecific clearance by circulation. These nanoparticles possess good cytotoxicity and hemocompatibiliy. Acidic environment (pH 5.0) triggers effective DOX release from FA-SND, 5-fold higher than does a neutral condition (pH 7.4). Further, FA-SND nanoparticles specifically target folate-receptor-rich KB cells, and endocytosed into lysosomes, an acidic organelle. The acidic microenvironment of lysosomes promotes a rapid release of DOX to nuclei, producing cancer specific chemo-cytotoxicity. Thus, FA-mediated cancer targeting and lysosomal-acidity promoting DOX release, two sequentially-occurring cellular events triggered by the designed components of FA-SND, form the basis for FA-SND to achieve its localized and intracellular chemo-cytotoxicity. Together, this study suggests that these FA-SND nanoparticles may be a potentially effective carrier particularly useful for delivering hydrophobic chemotherapeutic agents for treating cancers with high-level expression of folate receptors.Keywords
Funding Information
- Ministry of Education of the People's Republic of China (113044A)
- Ministry of Science and Technology of the People's Republic of China (S2014ZR0340)
- Huazhong University of Science and Technology (2015TS153)
- Natural Science Foundation of Hubei Province (2015CFA049)
- National Natural Science Foundation of China (81272559, 81441077, 81572866)
This publication has 46 references indexed in Scilit:
- A pH-sensitive doxorubicin prodrug based on folate-conjugated BSA for tumor-targeted drug deliveryBiomaterials, 2013
- Enzyme-responsive copper sulphide nanoparticles for combined photoacoustic imaging, tumor-selective chemotherapy and photothermal therapyChemical Communications, 2013
- Dendronized heparin−doxorubicin conjugate based nanoparticle as pH-responsive drug delivery system for cancer therapyBiomaterials, 2013
- Design of polymeric nanoparticles for biomedical delivery applicationsChemical Society Reviews, 2012
- Monitoring of inflammatory mediators induced by silk sericinJournal of Bioscience and Bioengineering, 2009
- Nanoparticle therapeutics: an emerging treatment modality for cancerNature Reviews Drug Discovery, 2008
- Therapeutic Nanoparticles for Drug Delivery in CancerClinical Cancer Research, 2008
- Natural polymers for gene delivery and tissue engineering☆Advanced Drug Delivery Reviews, 2006
- Chemotherapeutic engineering: Application and further development of chemical engineering principles for chemotherapy of cancer and other diseasesChemical Engineering Science, 2003
- Self-assembly of block copolymers derived from elastin-mimetic polypeptide sequencesAdvanced Drug Delivery Reviews, 2002