Bioactive Materials
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2021
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IF 14.593
Lanfang Ren,Yang Gao,Yiyun Cheng
Peptides have gained increasing interests as drug candidates in modern pharmaceutical industry, however, the development of peptide drugs acting on intracellular targets is limited due to their membrane impermeability. Here, we reported the use of metal-terpyridine based coordinative dendrimer for cytosolic peptide delivery. Among the investigated transition metal ions, Mn 2+ -coordinated polymer showed the highest delivery efficiency due to balanced peptide binding and release. It showed robust efficiency in the delivery of peptides with different charge property and hydrophobicity into various primary cells. The efficiency of Mn 2+ -terpyridine based polymer is superior to cell penetrating peptides such as oligoarginines. The material also delivered an autophagy-inducing peptide derived from Beclin-1 into cells and efficiently induced autophagy in the cells. This study provides a promising alternative to cell penetrating peptides for cytosolic peptide delivery.
研究领域:
药学
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材料科学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Advances
·
2020
·Vol. 6
·期 33
·
IF 13.117
Guangyu Rong,Changping Wang,Lijie Chen,Yang Yan,Yiyun Cheng
Cytosolic delivery of peptides remains a challenging task owing to their susceptibility to enzymatic degradation and the existence of multiple intracellular barriers. Here, we report a new strategy to address these issues by decoration of a fluorous tag on the terminal of cargo peptides. The fluorous-tagged peptides were assembled into nanostructures, efficiently internalized by cells via several endocytic pathways and released into the cytosol after endosomal escape. They were relatively stable against enzymatic degradation and showed much higher efficiency than nonfluorinated analogs and cell penetrant peptide–conjugated ones. The proposed strategy also efficiently delivered a proapoptotic peptide into specific sites in the cells and restored the function of cargo peptide after cytosolic delivery. The fluorous-tagged proapoptotic peptide efficiently inhibited tumor growth in vivo. This study provides an efficient fluorination strategy to promote the cytosolic delivery of peptides.
研究领域:
药学
·
生物化学
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细胞生物学
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生物技术
·
药物化学
✓ 已验证
DOI
高影响因子
Biomaterials Research
·
2025
·
IF 9.6
Shiqing Ma,Shiyu Yao,Yumeng Li,Yilin Yang,Tianyi Tong,Hong Zheng,Beibei Ma,Pengfei Wei,Zhengyi Di,Bo Zhao,Jiayin Deng
Polyetheretherketone (PEEK) is considered to be a potential material for oral implants due to its elastic modulus being similar to that of human cortical bone. However, the poor antibacterial, anti-inflammatory, and osseointegration properties of bioinert PEEK have hindered its clinical application. Therefore, this study designed and constructed a pH-responsive PEEK implant with a bilayer core–shell zeolitic imidazolate framework-8 (ZIF-8) structure loaded on its surface, with an antimicrobial peptide (KR12) encapsulated in the outer shell and an osteogenic peptide (osteogenic growth peptide ) encapsulated in its inner core. In this study, the bilayer core–shell ZIF-8 structure was confirmed to have pH-responsive properties. In vitro studies proved that the implant could promote bone marrow mesenchymal stem cells’ proliferation and differentiation and the M1 phenotype to M2 phenotype conversion of RAW 264.7 and could inhibit bacterial adhesion and proliferation. By constructing rats’ distal femur with/without infection models, it was further demonstrated that the novel implant could effectively inhibit bacterial adhesion and growth, inhibit inflammation, and promote peri-implant osseointegration, which was more substantial when the local area was infected and the pH was lower than that of normal tissue. Collectively, the results suggest that this novel pH-responsive PEEK implant loaded with a bilayer core–shell ZIF-8 structure is a promising peptide delivery implant system, which is well suited for dental applications and offers a potential solution for the prevention of infection during the early phase after implantation.
研究领域:
生物材料
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组织工程
·
牙科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Xin Gao,Chunyang Yuan,Echuan Tan,Zhan Li,Yiyun Cheng,Jianru Xiao,Guangyu Rong
Peptide drugs have been successfully used for the treatment of various diseases. However, it is still challenging to develop therapeutic peptides working on intracellular targets due to their poor membrane permeability. Here, we proposed a type of dual-responsive bioconjugates bearing a heterobifunctional adaptor containing both aldehyde and catechol moieties for efficient cytosolic peptide delivery. Hydrazine-terminated cargo peptides were tagged to a boronated dendrimer with the help of the adaptor via dynamic acylhydrazone and catechol‑boronate linkages. The bioconjugates efficiently delivered peptides with distinct physicochemical properties into various cells, and could release the cargo peptides triggered by intracellular reactive oxygen species and endolysosomal acidity, restoring the biofunctions of delivered peptides. In addition, the designed complexes efficiently delivered a pro-apoptotic peptide into osteosarcoma cancer cells and successfully inhibited the tumor growth both in vitro and in vivo . This study provides a universal and efficient platform for cytosolic therapeutic peptide delivery to intracellular targets for treating various diseases.
研究领域:
药学
·
药物递送系统
·
癌症研究
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Shuang Gao,Kaini Liang,Zejun Fan,Yanxiao Ao,Wen Liu,Wenjing Li,Yuanyuan Zhang,Yanan Du
Probiotics, recognized for their cost-effective production, easy storage, and straightforward delivery, are a key focus in developing innovative delivery systems for disease treatment. However, the limited delivery efficacy of probiotics and potential safety issues have hastened their broader application. In this study, a hydrogel encapsulation system is developed to improve the therapeutic efficiency of probiotics through subcutaneous administration. This encapsulation approach is proven to protect the probiotics, thus prolonging their lifetime and enhancing delivery efficiency. Besides, the growth of probiotics is limited within the hydrogel microparticle, which may reduce the adverse effects on the surrounding tissues. This probiotic therapy regimen is demonstrated in Exendin-4 delivery for diabetic treatment, as well as the delivery of thrombopoietin mimetic peptide for thrombocytopenia treatment. In summary, this system has shown the promising potential of probiotic encapsulation in improving the efficacy and safety of probiotic therapy in various diseases.
研究领域:
药物递送
·
生物医学工程
·
微生物学
·
治疗性多肽
·
生物材料
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）