ACS Applied Materials & Interfaces
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2024
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IF 8.3
Xikuang Yao,Changrui Sun,Fei Xiong,Weina Zhang,Wenjing Yao,Yinghui Xu,Wenpei Fan,Fengwei Huo
Nanomedicine-enhanced immunogenic cell death (ICD) has attracted considerable attention for its great potential in cancer treatment. Even though polyethylene glycol (PEG) is widely recognized as the gold standard for surface modification of nanomedicines, some shortcomings associated with this PEGylation, such as hindered cell endocytosis and accelerated blood clearance phenomenon, have been revealed in recent years. Notably, polysarcosine (PSar) as a highly biocompatible polymer can be finely synthesized by mild ring-opening polymerization (ROP) of sarcosine N-carboxyanhydrides (Sar-NCAs) and exhibit great potential as an alternative to PEG. In this article, PSar-b-polycamptothecin block copolymers are synthesized by sequential ROP of camptothecin-based NCAs (CPT-NCAs) and Sar-NCAs. Then, the detailed and systematic comparison between PEGylation and PSarylation against the 4T1 tumor model indicates that PSar decoration can facilitate the cell endocytosis, greatly enhancing the ICD effects and antitumor efficacy. Therefore, it is believed that this well-developed PSarylation technique will achieve effective and precise cancer treatment in the near future.
研究领域:
肿瘤学
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药剂学
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生物材料学
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DOI
PubMed
高影响因子
BIOCONJUGATE CHEMISTRY
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2018
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IF 4.485
Yali Hu,Yingqin Hou,Hao Wang,Hua Lu
The performance of many therapeutic proteins, including human interferon-α2b (IFN), is often impeded by their intrinsic instability to protease, poor pharmacokinetics, and strong immunity. Although PEGylation has been an effective approach to improve the pharmacokinetics of many proteins, a few noticeable limitations have aroused vast research efforts in seeking alternatives to PEG for bioconjugation. Herein, we report our investigation on the use of polysarcosine (PSar), a nonionic and hydrophilic polypeptoid, for IFN modification. The site-specific conjugate PSar-IFN, generated by native chemical ligation in high yield, is systematically compared with a similarly produced PEG–interferon conjugate (PEG-IFN) to evaluate the in vitro and in vivo behaviors. PSar is found to show comparable ability in stabilizing IFN from protease digestion in vitro and prolonging the circulation half-life in vivo. Interestingly, PSar-IFN retains more activity in vitro and accumulates more in the tumor sites upon systemic administration than PEG-IFN. Most importantly, PSar-IFN is significantly more potent in inhibiting tumor growth and elicits considerably less anti-IFN antibodies in mouse than PEG-IFN. Together, our results demonstrate for the first time that PSar is an outstanding candidate for therapeutic protein conjugation. Considering the low toxicity, biodegradability, and excellent stealth effect of PSar, this study suggests that such polypeptoids hold enormous potential for many biomedical applications including protein delivery, colloidal stabilization, and nanomedicine.
研究领域:
药物化学
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生物医学工程
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分子生物学
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药物递送系统
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DOI
PubMed
高影响因子
JOURNAL OF POLYMER SCIENCE
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2024
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IF 3.9
Runcheng Tan,Guangqi Huang,Cong Wei,Zepeng He,Tianyu Zhao,Yi Shi,Zhijia Liu,Yongming Chen
Lipid nanoparticles (LNPs) have been demonstrated to be potent and well-tolerated vehicles for delivering mRNA in vaccination and therapeutics. However, the presence of anti-poly(ethylene glycol) (PEG) antibodies in the body resulted in the problems of hypersensitivity reaction, accelerated blood clearance and high systemic reactogenicity after repeated dosing of PEG lipid-contained LNPs, thus limiting the utility for in vivo messenger RNA (mRNA) delivery. Here, we synthesized well-defined polysarcosine functionalized lipids (pSar-lipids) with various hydrophobic tail lengths and molecular weights by the accelerated ring-opening polymerization of sarcosine N -carboxyanhydride (NCA). The obtained pSar-lipids were utilized as PEG lipid alternatives to explore structure–activity relationships of pSar-lipid-based LNPs. The results demonstrated that pSar-lipid-based LNPs by intravenous administration represented higher mRNA delivery efficiency in the liver and spleen with the increased hydrophobic tail length of pSar-lipids. Importantly, more significant preference for mRNA delivery into the liver was identified by increasing the molecular weight of pSar segments. As a result, this work elucidated the effect of structural variations in pSar-lipids on LNP-mediated in vivo mRNA delivery, providing clues to optimize pSar-lipids as potential alternatives to PEG lipids for developing next-generation of LNP delivery systems. Graphical
研究领域:
生物技术
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医学
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分子生物学
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产品关联
DOI
高影响因子
International Journal of Nanomedicine
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2025
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IF 6.5
Weiwei Ma,Yan Zhang,Xuejing Zhai,Qian Qu,Xueying Guo,Sen Zhang,Ruiyao Hou,Ping Lu,Yanyan Yin
Background Graphene oxide (GO) has high drug-loading capacity and good photothermal property. However, the limited stability and poor biocompatibility of GO hindered its application as drug delivery carrier for future nanomedicine.Methods In this study, a new strategy of using chemical conjugation on GO with polypeptide was adopted. A novel Biotin grafted polysarcosine polymers (B-PSar) modified graphene oxide derivative (B-PSar-GO) was successfully synthesized and utilized as a carrier to develop a new drug delivery system for targeted chemo-photothermal cancer therapy. In vitro and in vivo experiments evaluated the system’s biosafety and antitumor efficacy.Results With the B-PSar protection, the B-PSar-GO showed excellent biological safety with the average size of 268.2±8.4 nm. Stability experiments displayed B-PSar-GO was extremely stable. The anti-cancer drug doxorubicin (DOX) was loaded on B-PSar-GO through π–π interactions and hydrophobic interactions, B-PSar-GO@DOX achieved a maximum loading capacity of 25.5%. In addition, B-PSar-GO@DOX exhibited NIR/pH dual-responsive DOX release characteristics, ensuring sustained drug release to tumor tissues triggered by NIR laser irradiation and acidic tumor microenvironment. Based on the excellent photothermal conversion efficiency of GO, B-PSar-GO@DOX showed excellent chemo-photothermal synergistic tumor inhibition both in vitro and in vivo under NIR irradiation.Conclusion The novel nano-drug delivery system B-PSar-GO@DOX developed in this paper offers a promising platform for chemo-photothermal synergistic cancer treatment.
研究领域:
纳米医学
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癌症治疗
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药物递送
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生物材料
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光热治疗
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2015
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IF 4.152
Jianwei Du,Ce Tian,Yajie Liu,Jun Ling,Youxiang Wang
Polypeptide has been extensively researched in gene/drug delivery system due to the good biocompatibility. Herein, we synthesized total-polypeptide copolymers, i.e. Azo(azobenzene)-capped polysarcosine- b -polylysine (ASL) with narrow molecular weight distribution by α-amino acid N-carboxyanhydride (NCA) polymerization. Although the molecular weight of PLL segment was only about 6 kDa, ASL could condense DNA effectively and form about 150 nm spherical nanoparticles at N/P ratio of 15. The surface charge was significantly reduced due to the shielding effect of polysarcosine (PSAR) shell. ASL/DNA PeptoPlexes showed good colloidal stability under physiological salt condition and complexation competition stability in the presence of counter polyanion, which might improve the circulation time in vivo . The tip design of azobenzene provided a facile way for ligand modification via host–guest interaction, which could be flexibly optimized by changing its functional tags responding to a request. Our data showed that the introduction of CD-R8 could promote the internalization of gene into cytoplasm and even nucleus owing to the membrane penetrating effect of R8. Cell culture experiments indicated as a total-polypeptide system, ASL showed good cellular viability and comparable gene transfection level as PLL with molecular weight of 50 kDa. Overall, PSAR served as an ideal alternative of PEG and this total-polypeptide system showed us a good direction for gene carrier design.
研究领域:
材料科学
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基因治疗
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
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