Self‐Assembling Doxorubicin Silk Hydrogels for the Focal Treatment of Primary Breast Cancer

Abstract

Standard care for early stage breast cancer includes tumor resection and local radiotherapy to achieve long-term remission. Systemic chemotherapy provides only low locoregional control of the disease; therefore, we describe self-assembling silk hydrogels that can retain and then deliver doxorubicin locally. Self-assembling silk hydrogels show no swelling, are readily loaded with doxorubicin under aqueous conditions and release drug over 4 weeks in amounts that can be fine-tuned by varying the silk content. Following successful in vitro studies, locally injected silk hydrogels loaded with doxorubicin show excellent antitumor response in mice, outperforming the equivalent amount of doxorubicin delivered intravenously. In addition to reducing primary tumor growth, doxorubicin-loaded silk hydrogels reduce metastatic spread and are well tolerated in vivo. Thus, silk hydrogels are well suited for the local delivery of chemotherapy and provide a promising approach to improve locoregional control of breast cancer.

From silk spinning in insects and spiders to advanced silk fibroin drug delivery systems

“…Viscous and concentrated SF solutions are stored in the glands of insects and spiders and biomimicry of selected aspects of these storage conditions may provide the necessary insight to control continuing crystallization during storage. Independent of the intended DDS -hydrogels [79], microparticles [27,80], films [81], nanoparticles [82,83] or three-dimensional scaffolds [26,41,84,85] -the formulation scientist interested in working with SF will be challenged by this control of b-sheet content during manufacture, storage, and application [4,86]. On the other hand, this feature has been exploited for sustained, controlled drug delivery, which has been demonstrated for many drugs, including biologics [27,84,87] and a direct correlation has been postulated for the overall b-sheet content and the diffusion coefficient through the SF biopolymer [81].…”

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

“…The surface of SF can be easily functionalized with cell marker proteins [19] making it highly suitable for targeted drug release to specific pathological sites [5,20]. Additionally, SF is capable of effectively entrapping instead of strongly absorbing the low molecular weight DoX which enables it to diffuse through SF structures [21,22]. The inherent ability of SF to slowly release DoX is a unique feature to this biomaterial [21].…”

“…Additionally, SF is capable of effectively entrapping instead of strongly absorbing the low molecular weight DoX which enables it to diffuse through SF structures [21,22]. The inherent ability of SF to slowly release DoX is a unique feature to this biomaterial [21]. In addition, SF is biodegradable from weeks to months by modifying its beta sheet content [23,24].…”

“…This tunable degradability allows for controlled drug release from SF structures [23]. 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.…”