Assessing the Potential of New Lignin-Based pH-Responsive Nanoparticles as Drug Carriers for Cancer Treatment

Abstract

In this study, we prepared new lignin-based pH-responsive nanoparticles (LG-M­(N)-PEG NPs) and their conjugates (LG-M­(N-DOX)-PEG NPs) by using polyethylene glycol (PEG), doxorubicin (DOX), and alkaline lignin. In these NPs, the PEG chains were conjugated to lignin by an UV irradiated thiol–ene click reaction. The hydrazine and β-thiopropionate bonds in the NPs could conduct pH-triggered release of both DOX and lignin at an acidic pH in the tumor cells. Results showed that LG-M­(N-DOX)-PEG NPs had a moderate particle size (48.3 ± 3.2 nm), significant cytotoxicity against 4T1 cells, and enhanced cellular uptake. Interestingly, the NPs without DOX (LG-M­(N)-PEG NPs) could increase intracellular reactive oxygen species generation, induce cell pyroptosis, and result in a selective cytotoxicity to cancer cells. While the LG-M­(N-DOX)-PEG NPs could deliver both lignin and DOX, they had favorable carrier-enhanced cytotoxicity and higher cancer cellular uptake compared to free DOX. Moreover, LG-M­(N-DOX)-PEG NPs exhibited a clear tumor-inhibiting effect in vivo. Therefore, the NPs described here have great potential application in the drug delivery system.

Lignin Smart Nanoparticles for Effective and Eco-Friendly Resource Recovery from Wastewater: Status, Challenges, and Opportunities

“…Primarily, they incorporated pH-responsive dynamic bonds (hydrazine and βthiopropionate bonds) to enable the targeted release of both lignin and doxorubicin for a dual anticancer effect. 158 In a similar study, Zhou et al 82 loaded doxorubicin into hollow enzymatic hydrolysable lignin in a THF/water system via hydrogen bonding, adsorption, and π−π and electrostatic interactions. Furthermore, Li et al 161 used esterified organosolv lignin to synthesize hollow microspheres with attached magnetic Fe 3 O 4 nanoparticles on their surface to load organic dyes (i.e., methylene blue and rhodamine B).…”

Lignocellulosic–biomolecules conjugated systems: green-engineered complexes modified by covalent linkers

“…5(a2)). [118][119][120] TEA is usually a base but can configure a linker in bioconjugate systems with xylan. Also, xylan and drugs bind through bioconjugation when a succinic anhydride linker reacts in a DCC/DMAP medium and connects xylan to curcumin and 5fluorouracil drug.…”

“…121,125 Besides drugs, gelatin (a polysaccharide) forms a xylan biconjugate system with ethylene glycol diglycidyl ether as a bridge; this Fig. 5 Bioconjugated systems of (a) lignin, 117,118 (b) xylan, 121 and (c) tannic acid. 122 linker has cyclical ether functional groups that form ether bonds between xylan and gelatin.…”

Antitumor Effects of Carrier-Free Functionalized Lignin Materials on Human Hepatocellular Carcinoma (HepG2) Cells

“…Another strategy involves the development of lignin nanoparticles (LNPs) for loading compounds such as benzazulene (BZL) or the naturally renewable drug resveratrol. This methodology holds the potential to provide drug protection and enhance their anticancer effectiveness. , Additionally, the encapsulation of the anticancer drug adriamycin (DOX) in lignin nanoparticles resulted in enhanced utilization of DOX and improved anticancer effects. , Moreover, water-soluble modifications of hydrolyzed lignin using benzene poly­(carboxylic acid) compounds (BP-Cx-1) have demonstrated multiple biological effects on neurotransmitter receptors, ligand-gated ion channels, and transporter proteins, thereby contributing to cancer treatment . Although these methods enhance drug availability and antitumor efficacy, lignin only serves as a passive carrier or active site provider, which limits its potential as a standalone antitumor biomaterial.…”