Light-Responsive Serinol-Based Polycarbonate and Polyester as Degradable Scaffolds

Abstract

Stimuli-responsive self-immolative aliphatic polycarbonates (APCs) and polyesters (APEs) have attractive advantages for biomedical and pharmaceutical applications. In the present work, polycondensation of o-nitrobenzyl-protected serinol was explored as a simple route to obtain light-responsive polycarbonate (LrPC) and polyester (LrPE). By exposure to UV light, these polymers decomposed rapidly and completely into oligomers and small molecules, as detected by size exclusion chromatography (SEC), UV/vis, and 1H nuclear magnetic resonance (NMR) spectroscopies. The degradation mechanism of serinol-based APC and APE was investigated with the help of the Boc-protected model APC and APE, showing that the APC underwent intramolecular cyclization, accompanied by intermolecular transcarbamation, and degraded into oxazolidinone and 2-aminopropanol terminated oligourethanes. Different from APC, the degradation process of serinol-based APE has been proven by electrospray ionization time-of-flight mass spectrometry (ESI-ToF-MS) to follow intramolecular cyclization of the functional amine group with the remote ester group, forming a ten-membered cyclic degradation compound. Further processing of the serinol-based polymers was performed by preparation of nanoparticles (NP). With light-responsive characteristics, a drug delivery system could be potentially obtained enabling a controllable drug release. Based on this strategy, a variety of self-immolative polymers responsive to different triggers can be prepared by polycondensation without the limit of ring-opening polymerization and will expand the family of biodegradable polymers.

Remote Light‐Responsive Nanocarriers for Controlled Drug Delivery: Advances and Perspectives

“…By exploiting similar strategy, Kuckling and Sun have recently developed a new light‐responsive aliphatic polycarbonate (LrPC) for delivery of the photosensitizer 5,10,15,20‐tetrakis (m‐hydroxyphenyl)chlorin (mTHPC) ( Figure ). Multiple photocleavable oNB groups were conjugated within this LrPC polymer as side chains . UV light irradiation (λ = 320–480 nm) resulted in the cleavage of the oNB protecting groups, followed by the rapid degradation of the polymers via intramolecular cyclization.…”

In Vivo Degradation Mechanisms of Aliphatic Polycarbonates and Functionalized Aliphatic Polycarbonates

“…This polymer was designed for application as a stimuli-responsive nanoparticulate drug delivery system for hydrophobic drugs. In a similar approach, an APC was formed that degraded upon photo-activated cleavage of a protecting group to yield a primary amine [113][114][115] (Figure 11H) to produce nanoparticles to be used in photodynamic therapy.…”

Stimuli-Responsive Aliphatic Polycarbonate Nanocarriers for Tumor-Targeted Drug Delivery

“…Similarly, Fang et al [146] reported photo-responsive micelles consisting of PNIPAM-b-poly(3-methyl-3-nitrobenzyl-trimethylene carbonate) for indomethacin drug delivery system. Likewise, Kuckilng and coworkers developed a series of light-degradable nanocarriers consisting of PEGylated APC with an o-nitrobenzyl ester group as side chains [147][148][149][150][151]. The nanoparticles were prepared from mixing amphiphilic APC copolymer with poly(lactide-co-glycolide) in ratio 1:3 (Figure 9).…”

“…Preliminary in vitro cellular studies of the above-mentioned nanoparticles and degradation products confirmed that systems have the potential to be used for in vivo studies. [147][148][149][150][151]. The nanoparticles were prepared from mixing amphiphilic APC copolymer with poly(lactide-co-glycolide) in ratio 1:3 ( Figure 9).…”