Abstract
Osteosarcoma therapy might be moving toward nanotechnology-based drug delivery systems to reduce the cytotoxicity of antineoplastic drugs and improve their pharmacokinetics. In this paper, we present, for the first time, an extensive chemical and in vitro characterization of dual-loaded photo- and chemo-active keratin nanoparticles as a novel drug delivery system to treat osteosarcoma. The nanoparticles are prepared from high molecular weight and hydrosoluble keratin, suitably functionalized with the photosensitizer Chlorin-e6 (Ce6) and then loaded with the chemotherapeutic drug Paclitaxel (PTX). This multi-modal PTX-Ce6@Ker nanoformulation is prepared by both drug-induced aggregation and desolvation methods, and a comprehensive physicochemical characterization is performed. PTX-Ce6@Ker efficacy is tested on osteosarcoma tumor cell lines, including chemo-resistant cells, using 2D and 3D model systems. The single and combined contributions of PTX and Ce6 is evaluated, and results show that PTX retains its activity while being vehiculated through keratin. Moreover, PTX and Ce6 act in an additive manner, demonstrating that the combination of the cytostatic blockage of PTX and the oxidative damage of ROS upon light irradiation have a far superior effect compared to singularly administered PTX or Ce6. Our findings provide the proof of principle for the development of a novel, nanotechnology-based drug delivery system for the treatment of osteosarcoma.
Highlights
Osteosarcoma (OS) is the most common type of bone sarcoma diagnosed in childhood [1]
We present, for the first time, an extensive chemical and in vitro characterization of dual-loaded photo- and chemo-active keratin nanoparticles as a novel drug delivery system to treat osteosarcoma
Our findings provide the proof of principle for the development of a novel, nanotechnology-based drug delivery system for the treatment of osteosarcoma
Summary
Osteosarcoma (OS) is the most common type of bone sarcoma diagnosed in childhood [1]. A comparative in vivo study demonstrated that the at high-dose of AbraxaneTM (e.g., 40 mg/kg) induced a tumor inhibitory rate of 98.8%, as compared to Taxol® (40.8%) and Adryamicin (46.1%) [21] These encouraging results indicate that nanotechnology-based DDS for PTX could represent a promising therapeutic option for OS treatment. High molecular weight and hydrosoluble keratin was selected for preparing nanoformulations functionalized with both PTX and Ce6 as a novel approach for the pharmacological treatment of OS This novel bimodal nanoformulation that combines chemo and photodynamic therapies, was generated with the aim to deliver PTX to cancer cells, while decreasing its general toxicity and scarce intracellular accumulation, and to provide a second therapeutic agent to wipe out OS cells that might have survived the PTX or become chemo-resistant
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
