Size-controllable dual drug-loaded silk fibroin nanospheres through a facile formation process

The continual generation of drug resistance is a major challenge in clinical cancer chemotherapy. Combination drug therapy may overcome such limitations by minimizing the required dosage of each drug whilst achieving an enhancement of therapeutic efficacy. Regenerated silk fibroin (RSF) is a commonly used drug delivery platform due to its suitable biocompatibility, controllable biodegradability, and diverse material formats. Herein, dual drug-loaded RSF nanospheres were prepared using a facile and green method to deliver two anti-cancer drugs with distinct physical properties, namely hydrophobic paclitaxel (PTX) and hydrophilic doxorubicin (DOX). The particle size of the PTX/DOX-loaded RSF nanospheres was easily regulated, by varying the RSF and ethanol concentrations during the formation process, from approximately 100 to 600 nm, with subsequent applications in both intravenous and lymphatic chemotherapy. The drug release profile of both PTX and DOX in the PTX/DOX-loaded RSF nanospheres was found to be well controlled and sustained for over 7 days. Further, the dual drug-loaded RSF nanospheres exhibited a high cellular uptake via endocytosis. Importantly, the dual drug-loaded RSF nanospheres showed more efficient suppression of cancer cell growth than the single drug-loaded RSF nanospheres with either drug or the free drugs at the same concentration, particularly at a DOX/PTX ratio of 1 : 1. Thus, the prepared dual drug nanocarrier with a controllable particle size may have important clinical implications for combination chemotherapy.