Functionalized silk spheres selectively and effectively deliver a cytotoxic drug to targeted cancer cells in vivo
- PDF / 3,231,073 Bytes
- 18 Pages / 595.276 x 790.866 pts Page_size
- 42 Downloads / 196 Views
Journal of Nanobiotechnology Open Access
RESEARCH
Functionalized silk spheres selectively and effectively deliver a cytotoxic drug to targeted cancer cells in vivo Anna Florczak1,2*, Tomasz Deptuch1,2, Anna Lewandowska3,4, Karolina Penderecka1,2, Elzbieta Kramer3, Andrzej Marszalek3,4, Andrzej Mackiewicz1,2 and Hanna Dams‑Kozlowska1,2*
Abstract Background: Chemotherapy is often a first-line therapeutic approach for the treatment of a wide variety of cancers. Targeted drug delivery systems (DDSs) can potentially resolve the problem of chemotherapeutic drug off-targeting effects. Herein, we examined in vivo models to determine the efficacy of Her2-targeting silk spheres (H2.1MS1) as DDSs for delivering doxorubicin (Dox) to Her2-positive and Her2-negative primary and metastatic mouse breast cancers. Results: The specific accumulation of H2.1MS1 spheres was demonstrated at the site of Her2-positive cancer. Dox delivered only by functionalized H2.1MS1 particles selectively inhibited Her2-positive cancer growth in primary and metastatic models. Moreover, the significant effect of the Dox dose and the frequency of treatment administration on the therapeutic efficacy was indicated. Although the control MS1 spheres accumulated in the lungs in Her2-positive metastatic breast cancer, the Dox-loaded MS1 particles did not treat cancer. Histopathological examination revealed no systemic toxicity after multiple administrations and at increased doses of Dox-loaded silk spheres. Although the studies were performed in immunocompetent mice, the H2.1MS1 silk spheres efficiently delivered the drug, which exerted a therapeutic effect. Conclusion: Our results indicated that functionalized silk spheres that enable cell-specific recognition, cellular inter‑ nalization, and drug release represent an efficient strategy for cancer treatment in vivo. Keywords: Silk, Particles, Functionalization, Bioengineering, Targeted drug delivery, Cancer, Mouse cancer models Background Chemotherapy is often a first-line therapeutic approach for the treatment of a wide variety of cancers [1, 2]. However, nonspecific delivery of chemotherapeutic agents leads to undesirable side effects in healthy tissues and dosages that are insufficient to kill cancer cells. Therefore, various targeted drug delivery systems have been investigated [3] to overcome these difficulties. *Correspondence: [email protected]; hanna.dams‑[email protected] 1 Chair of Medical Biotechnology, Poznan University of Medical Sciences, 15 Garbary St, 61‑866 Poznan, Poland Full list of author information is available at the end of the article
Nanomaterial-based drug delivery systems (DDSs) deliver therapeutic agents to specific organs or tissues using nanoscale particles to circumvent the nonspecific biodistribution of free drugs [4, 5]. A DDS should be characterized by simple preparation, high drug loading capacity, and excellent stability [6, 7]. Silk biomaterials are considered to be great candidates for various biomedical applications, as they are biocompatible, biodegradable,
Data Loading...
