pH‐Dependent Anticancer Drug Release from Silk Nanoparticles

Abstract

Silk has traditionally been used as a suture material because of its excellent mechanical properties and biocompatibility. These properties have led to the development of different silk-based material formats for tissue engineering and regenerative medicine. Although there have been a small number of studies about the use of silk particles for drug delivery, none of these studies have assessed the potential of silk to act as a stimulus-responsive anticancer nanomedicine. This report demonstrates that an acetone precipitation of silk allowed the formation of uniform silk nanoparticles (98 nm diameter, polydispersity index 0.109), with an overall negative surface charge (-33.6 ±5.8 mV), in a single step. Silk nanoparticles were readily loaded with doxorubicin (40 ng doxorubicin/μg silk) and showed pH-dependent release (pH 4.5>> 6.0 > 7.4). In vitro studies with human breast cancer cell lines demonstrated that the silk nanoparticles were not cytotoxic (IC50 >120/μ/ml) and that doxorubicin-loaded silk nanoparticles were able to overcome drug resistance mechanisms. Live cell fluorescence microscopy studies showed endocytic uptake and lysosomal accumulation of silk nanoparticles. In summary, the pH-dependent drug release and lysosomal accumulation of silk nanoparticles demonstrated the ability of drug-loaded silk nanoparticles to serve as a lysosomotropic anticancer nanomedicine.

Doxorubicin loaded nanodiamond-silk spheres for fluorescence tracking and controlled drug release

“…SF-based delivery carriers often show drug release characteristics that are governed mostly by solubilisation or degradation of the SF [6]. For the present case, the degradation of SF reduced the sphere size as shown in Section 3.2, affecting the emission properties of NDs on the encapsulated spheres which was investigated during the drug release.…”

“…Furthermore, drug carriers are expected to stay in the blood for an extended period of time and then accumulate at diseased sites [4]. Current studies [1,3,5,6] have identified that nanoparticles (NPs) not only have the ability to be used as targeted drug delivery platforms but they can also overcome drug resistance through the enhanced permeation and retention (EPR) effect [6]. For NP based drug delivery systems [5], the EPR effect facilitates the deposition of nanoparticles at the tumour site due to the tumour's leaky vasculature, abnormal growth and lack of an effective lymphatic drainage [5,7].…”

“…Recent studies [6,21,22] have revealed that DoX loaded SF structures are able to overcome the DoX resistance mechanisms of breast cancer cells by improving the cellular uptake mechanism. Drug loaded SF structures are able to inhibit cell growth significantly more than the free drug at the DoX equivalent dose [6].…”

“…Although drug loaded SF carriers have been investigated [6,21], there have been no studies that reported the dual mixing of drugs and imaging agents in SF nanospheres. Here we report the fabrication and characterization of imaging enabled DoX incorporated SF (NDSX) spheres.…”

Self-assembled silk fibroin nanoparticles loaded with binary drugs in the treatment of breast carcinoma

“…[37][38][39][40][41][42] As a drug carrier, the SF molecules possess controllability of their degradation under in vitro and in vivo, which can be regulated by changing its size, crystallinity, molecular weight, and degree of cross-linking. 43,44 The hydrophobic amino acid residues in SF molecules, such as alanine, glycine, and tyrosine, can enhance the entrapping of curcumin and 5-FU through hydrophobic interaction and π-π packing, which increase the loading efficacy of the binary drug carrier. Besides, the hydrophilic amino acid residues in SF molecules, such as serine, aspartic acid, and glutamate, increase their water solubility and induce the formation of nanoparticles in aqueous solutions.…”