Structure and Oxidation Effects on Conformation and Thermoresponsiveness of the OEGylated Poly(glutamic acid)-Bearing Side-Chain Thioether Linkers.

A series of side-chain thioether-linked OEGylated poly(glutamic acid) (PGAs) have been synthesized by "thiol-ene" synthetic methodology, where both the oligo-ethylene glycol (OEG) length and the hydrophobic linkers at the side chains are varied to learn how these structural features affect the secondary structure and thermoresponsive behaviors in water. Before side-chain oxidation, the structural factors affecting the α-helicity include the backbone length, the OEG length, and the hydrophobic linkers' length at the side chains; however, the OEG length plays the most crucial role among these factors because longer OEG around the peripheral side chains can stop water penetration into the backbone to disturb the intramolecular H bonds, which finally allows stabilizing the α-helix; after the oxidation, the polypeptides show increased α-helicity because of the enhanced hydrophilicity. More interestingly, a rare oxidation-induced conformation transition from the ordered ß-sheet to the ordered α-helix can be achieved. In addition, only the OEGylated poly(glutamic acids) (PGAs) with shorter hydrophobic linkers and longer OEG can display the thermoresponsive properties before the oxidation but the subsequent oxidation can cause the polypeptides bearing longer hydrophobic linkers to exhibit the thermosensitivity since sulfone formation at the side chain can lead to final hydrophilicity-hydrophobicity balance. This work is meaningful to understand the secondary structure-associated solution behaviors of the synthetic polypeptides.

Bismuth nanoclusters on nitrogen-doped porous carbon nanoenzyme for cancer therapy.

Among the emerging cancer therapeutic methods, nanocatalytic therapy through the rational design of nanozymes is considered to be a promising strategy. However, high-performance nanozymes with the ability to catalyze the production of toxic substances to efficiently kill cancer cells are still highly desired. Herein, we fabricate bismuth nanoclusters loaded on nitrogen-doped porous carbon (Bi-NC) as a nanozyme for cancer therapy. The Bi-NC nanozyme displays both peroxidase (POD) and glutathione oxidase (GSHOx) biomimetic enzymatic activities, especially in a tumor microenvironment (TME), which catalyzes the production of hydroxyl radicals (·OH) and depletes antioxidant glutathione (GSH), simultaneously. Moreover, Bi-NC exhibits good photothermal conversion performance under near-infrared light irradiation. After surface modification with hyaluronic acid (HA) to improve the dispersity of nanoparticles and their accumulation in tumor tissues, Bi-NC@HA exhibits remarkable antitumor effects through the synergistic effect of catalytic and photothermal therapy. This work provides a new pathway for designing high-performance nanozymes for cancer catalytic therapy.

Guanidinylated Cyclic Synthetic Polypeptides Can Effectively Deliver siRNA by Mimicking the Biofunctions of Both Cell-Penetrating Peptides and Nuclear Localization Signal Peptides.

Preventing endosomal entrapment of gene/vector nanocomplexes (NCs) remains a challenge for highly effective siRNA delivery. To address this problem, guanidinylated cyclic synthetic polypeptides (GCSPs) were synthesized using an efficient and easy method. GCSPs can condense siRNAs into NCs with an encapsulation efficiency of approximately 90%, over twice the effectiveness of Lipofectamine2000 (Lipo2000). The NCs can also mediate luciferase knockdown in HeLa cells with a silencing efficiency of 80%, nearly 2- and 1.1-fold that of Lipo2000 and PEI, respectively. More importantly, the NCs can enter cells by mimicking the bioactivity of cell-penetrating peptides (CPPs). NCs can also exert a nuclear localized function similar to nuclear localization signal peptides (NLSPs). Both biofunctions are helpful for preventing the common endosomal entrapment of NCs and greatly enhance the efficiency of siRNA delivery.