Antitumor properties of platinum(iv) prodrug-loaded silk fibroin nanoparticles

Abstract

Platinum(iv) complexes take advantage of the exclusive conditions that occur within the tumor to carry out their cytotoxic activity. On the other hand, silk fibroin has natural properties which make it very interesting as a biomaterial: high biocompatibility, biodegradability, low immunogenicity, high cellular penetration capacity and high reactive surface. Herein we report the preparation of silk fibroin nanoparticles (SFNs) loaded with the hydrophobic Pt(iv) complex cis,cis,trans-[Pt(NH(3))(2)Cl(2)(O(2)CC(6)H(5))(2)] (PtBz). Only a small fraction of the loaded PtBz is released (less than 10% after 48 h). PtBz-SFNs trigger strong cytotoxic effects against human ovarian carcinoma A2780 cells and their cisplatin-resistant variant A2780cisR cells. Interestingly, PtBz-SFNs are very cytotoxic (nanomolar IC(50) values) toward the triple negative breast tumor cell line MDA-MB-231, and also toward SK-BR-3 and MCF-7, while maintaining an excellent selectivity index.

Modulation of vincristine and doxorubicin binding and release from silk films

“…Silk fibroin protein from silkworm cocoons (referred to hereon as silk) has been studied for the release of a variety of therapeutic small molecules [20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32]. Chemotherapy agents such as doxorubicin and platinum-based drugs reversibly bind to silk resulting in sustained release in vitro and in vivo [26, 27, 28, 29, 30, 31, 32].…”

“…Chemotherapy agents such as doxorubicin and platinum-based drugs reversibly bind to silk resulting in sustained release in vitro and in vivo [26, 27, 28, 29, 30, 31, 32]. New options to modify and tune the binding and release of drugs from silk would enhance the utility of this protein material in drug delivery.…”

Implantable chemotherapy-loaded silk protein materials for neuroblastoma treatment

“…Silk fibroin‐based materials have gained considerable interest in supporting the bioactivity and delivery of many therapeutic molecules including oncology therapeutics . Additionally, silk protein‐based materials have been used clinically for centuries as a suture material and more recently has gained FDA approval as a bioresorbable scaffold for soft tissue support and to reinforce tissue deficiencies .…”

“…7 Silk fibroin-based materials have gained considerable interest in supporting the bioactivity and delivery of many therapeutic molecules including oncology therapeutics. [8][9][10][11][12][13][14][15][16][17] Additionally, silk protein-based materials have been used clinically for centuries as a suture material and more recently has gained FDA approval as a bioresorbable scaffold for soft tissue support and to reinforce tissue deficiencies. 18 Furthermore, materials developed from silk fibroin isolated from Bombyx mori silkworm cocoons exhibit minimal immune response in vivo, 19,20 are fully biodegradable 19,21 and is processed via all aqueous techniques.…”

Novel non-mulberry silk fibroin nanoparticles with enhanced activity as potential candidate in nanocarrier mediated delivery system

“…for successful carrier-based delivery systems were extensively reported (Table 1). 2,3,[11][12][13][14][15][16][17] The non-mulberry silk broin nanoparticles (SFNps) from Antheraea mylitta and Antheraea pernyi have been explored as nanocarriers for effective delivery system. [18][19][20][21][22] Non-mulberry SF is advantageous over mulberry SF because of the presence of inherent tripeptide sequence Arg-Gly-Asp (RGD) that favours better cell attachment and proliferation through intrinsic binding protein.…”