Polypeptides with High Zwitterion Density for Safe and Effective Therapeutics

Abstract

The commonly used "stealth material" poly(ethylene glycol) (PEG) effectively promotes the pharmacokinetics of therapeutic cargos while reducing their immune response. However, recent studies have suggested that PEG could induce adverse reactions, including the emergence of anti-PEG antibodies and tissue histologic changes. An alternative stealth material with no or less immunogenicity and organ toxicity is thus urgently needed. We designed a polypeptide with high zwitterion density (PepCB) as a stealth material for therapeutics. Neither tissue histological changes in liver, kidney, or spleen, nor abnormal behavior, sickness or death was induced by the synthesized polymer after high-dosage administration for three months in rats. When conjugated to a therapeutic protein uricase, the uricase-PepCB bioconjugate showed significantly improved pharmacokinetics and immunological properties compared with uricase-PEG conjugates.

Self‐Amplified Photodynamic Therapy through the 1O2‐Mediated Internalization of Photosensitizers from a Ppa‐Bearing Block Copolymer

“…Synthesis and Self-Assembly of POEGMA-b-P(MAA-co-VSPpaMA) Block Copolymer Thes ynthesis of POEGMA-b-P(MAA-co-VSPpaMA) block copolymer is illustrated in Schemes S1 and S2 in the Supporting Information. Theb iocompatible POEGMA [23] was first prepared by RAFT polymerization of OEGMA, and then tBMA was selected as the second monomer to prepare POEGMA-b-PtBMA block copolymer by using POEGMA as the macro-RAFT agent. Gel permeation chromatography (GPC,S upporting Information, Figure S1) and 1 [24] to produce VSPpa-OH by Steglich esterification, and then VSPpa-OH was further conjugated to the POEGMA-b-PMAA block copolymer to obtain the 1 O 2responsive POEGMA-b-P(MAA-co-VSPpaMA) block copolymer (denoted VSP).…”

Zwitterionic Polymer Coating of Sulfur Dioxide‐Releasing Nanosystem Augments Tumor Accumulation and Treatment Efficacy

“…MON‐DN@PCBMA were fabricated by a modified reflux‐precipitation polymerization method . In a typical route, 20 mg of MON‐DN, 95 mg of CBMA monomer, 4 mg of AIBN, 5 mg of BAC, and 40 mL of acetonitrile were mixed and stirred at 90 °C for 1 h under an atmosphere of N 2 .…”

“…Therefore, surface coating of a zwitterionic polymer may increase the blood circulation of nanoplatforms. However, the currently used zwitterionic polymer coatings are mainly concentrated on linear zwitterionic polymer chains, which might not be enough to conceal the nanoparticle surface completely . Benetti and co‐workers found that small plasma proteins such as bovine serum albumin (BSA), can physisorb on linear brush shells composed of poly‐2‐ethyl‐2‐oxazoline (PEOXA).…”

The Importance of Poly(ethylene glycol) Alternatives for Overcoming PEG Immunogenicity in Drug Delivery and Bioconjugation

“…After 24 and 72 h, free uricase underwent rapid clearance from circulation, while the uricase-modified PepCB and PEGylated uricase showed sustained activity, with the uricase-modified PepCB achieving the longest half-life. This phenomenon was likely due to the stronger hydration effect of carboxybetaine groups in comparison to ethylene glycol units, highlighting the advantageous properties of zwitterionic PepCB over conventional PEG [79].…”

“…The authors concluded that zwitterionic materials, as the next generation of biomaterials, open new avenues for the design and synthesis of anti-fouling agents for therapeutic drug delivery. Zhang et al interrogated an alternative stealth material consisting of polypeptides with a high zwitterion density (PepCB) (Figure 8a) by utilizing uricase as a model protein to examine the different pharmacokinetic and immunological profiles of uricase-modified PepCB and PEGylated uricase in rats in vivo [79]. After 24 and 72 h, free uricase underwent rapid clearance from circulation, while the uricase-modified PepCB and PEGylated uricase showed sustained activity, with the uricase-modified PepCB achieving the longest half-life.…”