Facile Preparation of Paclitaxel Loaded Silk Fibroin Nanoparticles for Enhanced Antitumor Efficacy by Locoregional Drug Delivery

Abstract

Non-toxic, safe materials and preparation methods are among the most important factors when designing nanoparticles (NPs) for future clinical application. Here we report a novel and facile method encapsulating anticancer drug paclitaxel (PTX) into silk fibroin (SF), a biocompatible and biodegradable natural polymer, without adding any toxic organic solvents, surfactants or other toxic agents. The paclitaxel loaded silk fibroin nanoparticles (PTX-SF-NPs) with a diameter of 130 nm were formed in an aqueous solution at room temperature by self-assembling of SF protein, which demonstrated mainly silk I conformation in the NPs. In cellular uptake experiments, coumarin-6 loaded SF NPs were taken up efficiently by two human gastric cancer cell lines BGC-823 and SGC-7901. In vitro cytotoxicity studies demonstrated that PTX kept its pharmacological activity when incorporating into PTX-SF-NPs, while SF showed no cytotoxicity to cells. The in vivo antitumor effects of PTX-SF-NPs were evaluated on gastric cancer nude mice exnograft model. We found that locoregional delivery of PTX-SF-NPs demonstrated superior antitumor efficacy by delaying tumor growth and reducing tumor weights compared with systemic administration. Furthermore, the organs of mice in NP treated groups didn't show obvious toxicity, indicating the in vivo safety of SF NPs. These results suggest that SF NPs are promising drug delivery carriers, and locoregional delivery of SF NPs could be a potential future clinical cancer treatment regimen.

Strengthening Gastric Cancer Therapy by Trastuzumab-Conjugated Nanoparticles with Simultaneous Encapsulation of Anti-MiR-21 and 5-Fluorouridine

“…The cytotoxic potential of NPs was evaluated by MTT assay as previously described [32]. NUGC4 and SGC7901 cells were incubated overnight in 96-well culture plates at a density of 4000 cells/well, and treated differently to analyze cell proliferation.…”

Silk fibroin nanoparticle as a novel drug delivery system

“…Another reason was that the release speed was depended on the drug payload and drug density in the nanoparticles, which was higher paclitaxel loading leading to faster release. Additionally, SF nanoparticles could be taken up by human gastric cancer cells and paclitaxel released from paclitaxel-SF-nanoparticles kept its pharmacological activity [243]. SF nanospheres have also been used for paclitaxel delivery.…”

Gelatinases-stimuli nanoparticles encapsulating 5-fluorouridine and 5-aza-2′-deoxycytidine enhance the sensitivity of gastric cancer cells to chemical therapeutics

“…The cytotoxic potential of NPs was evaluated by MTT assay as previously described [25]. Cells were plated in 96-well plates at a density of 4000 cells per well and incubated for 24 hours.…”