pH-responsive keratin nanoparticles for the controlled delivery of doxorubicin: a thorough physicochemical and in vitro study

Introduction Doxorubicin (DOX) is one of the most effective cytotoxic drug used for the treatment of a wide range of tumors. However, the use of DOX is limited by serious drawbacks, which might be partially overcome by means... [ view full abstract ]

Introduction

Doxorubicin (DOX) is one of the most effective cytotoxic drug used for the treatment of a wide range of tumors. However, the use of DOX is limited by serious drawbacks, which might be partially overcome by means of drug delivery systems based on nanotechnology. Keratin possesses excellent biocompatibility and low toxicity to cells;¹ moreover, specific aminoacidic sequences are present on the protein backbone, e.g. “Arg-Gly-Asp” (RGD) and “Leu-Aps-Val” (LDV), which are known to specifically bind to integrins receptors over-expressed in several cancer cells.² Therefore, in the present work we describe the synthesis, physicochemical and in vitro biological characterization of DOX-loaded keratin nanoparticles (DOX-KNPs) against breast cancer cells.

Methods

Stable and monodisperse DOX-KNPs were prepared through two diverse in-water methods, e.g. ionic gelation and aggregation, and characterized in terms of size, zeta-potential, morphology, stability in physiological media and drug release profiles. Mathematical models were applied to experimental data with the aim of understanding the release mechanism of DOX. Finally, antiproliferative activity against MCF7 and MDA MB 231 cells was evaluated in 2D models and compared with those of free DOX.

Results

KNPs-DOX1 and KNPs-DOX2 are obtained in quantitative yield by ionic gelation and aggregation method, respectively and with a drug loading ratio up to 30% wt. They are spherical in shape with hydrodynamic diameters of about 180 nm and a DOX release profile dependent on pH conditions (Fig. 1). In vitro biological evaluation highlighted the ability of KNPs-DOX to enter cancer cells more efficiently of free DOX and to inhibit their proliferation with IC₅₀ values comparable to those of the free drug (Fig. 2).

Discussion

In the present work, the ability of keratin extracted from raw wool to function as carrier of doxorubicin was explored by exploiting two diverse yet quantitative methods. Overall, data demonstrate the effectiveness or our newly synthesized keratin nanoparticles in delivering the drug, paving the way for a thorough investigation on the use of keratin nanoparticles as carriers of hydrophilic and toxic anticancer drugs.

References

1. X. Zhi, et al. RSC Adv., 2015, 5, 82334

2. B. Yu, et al. Mol. Membr. Biol. 2010, 27, 286