Tunable Bifunctional Silyl Ether Cross-Linkers for the Design of Acid-Sensitive Biomaterials

Abstract

Responsive polymeric biomaterials can be triggered to degrade using localized environments found in vivo. A limited number of biomaterials provide precise control over the rate of degradation, the release rate of entrapped cargo, and yield a material that is intrinsically non-toxic. Here we design non-toxic acid-sensitive biomaterials based on silyl ether chemistry. A host of silyl ether cross-linkers were synthesized and molded into relevant medical devices including Trojan horse particles, sutures, and stents. The resulting devices were engineered to degrade under acidic conditions known to exist in tumor tissue, inflammatory tissue, and within diseased cells. The implementation of silyl ether chemistry gave precise control over the rate of degradation, and depending upon the steric bulk around the silicon atom, afforded devices that could degrade over the course of hours, days, weeks, or months. These novel materials could be useful for numerous biomedical applications including drug-delivery, tissue repair, and general surgery.

Silylated Precision Particles for Controlled Release of Proteins

“…Silyl ethers have also been successfully used for reversibly cross-linking precision particles made from hydroxyethyl acrylate and controlling the release kinetics based on the pH of the environment and size of the substituents on the silicon atom. 39 …”

Synthesis of Acid-Labile PEG and PEG-Doxorubicin-Conjugate Nanoparticles via Brush-First ROMP

“…20−23 They can be readily prepared via addition of alcohols to dichlorosilanes; their rates of hydrolysis can be precisely tuned through choice of Si substituents. 20 Thus, we began our study with the synthesis of a panel of silyl ether-based bis-norbornene derivatives ( 1 – 4 , Figure 1b). These compounds were prepared in 35–76% yield via exposure of 4-hydroxymethyl-4-aza-tricyclo[5.2.1.0 2,6 ]dec-8-ene- exo -3,5-dione 24 to the corresponding dichlorosilane in the presence of N , N -diisopropylethylamine (see Supporting Information for synthetic details).…”

Stimuli‐Responsive Materials for Controlled Release of Theranostic Agents

“…A number of acid-labile linkers have been incorporated into the carriers for this purpose, including hydrazone, [42] acetal, [43] ketal, [44] orthoester, [45, 46] vinylester, [47] thiopropionate, [48] anhydride, [49] and silyl ether. [50] Additionally, some polymeric carriers whose hydrophilicity/hydrophobicity or structural conformation is sensitive to pH changes have been developed for pH-triggered release. [51, 52] …”