DataVXACS Applied Materials & InterfacesPaper
journal article·2024-09-18

In Situ Heparan Sulfate-Induced Peptide Self-Assembly to Overcome the Cell Surface Glycocalyx Barrier for Cancer Treatment

Pengfei Pei, Long Chen, Xinyao Guan, Peng Wei, Xiaoxu Kang, Lili Gong, Lihong Liu, Wenxu Guo, Renji Gu, Lixin Wang, Chuanke Zhao, Jun F. Liang, Shi-Zhong Luo

ACS Applied Materials & Interfaces· Volume 16· Issue 37
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Source abstract

Abstract

Heparan sulfate (HS) is a major component of cell surface glycocalyx with extensive negative charges and plays a protective role by preventing toxins, including small molecule drugs and anticancer cationic lytic peptides (ACLPs), from cells. However, this effect may compromise the treatment efficiency of anticancer drugs. To overcome the impedance of cancer cell glycocalyx, an HS-targeting ACLP PTP-7z was designed by fusion of an ACLP and a Zn 2+ -binding HS-targeting peptide. Upon Zn 2+ ion binding, PTP-7z could self-assemble into uniform nanoparticles and show improved serum stability and reduced hemolysis, which enable it to self-deliver to tumor sites. The peptide PTP-7z showed a pH- and Zn 2+ ion-dependent HS-binding ability, which triggers the HS-induced in situ self-assembling on the cancer cell surface in the acidic tumor microenvironment (TME). The self-assembled PTP-7z can overcome the impedance of cell glycocalyx by either disrupting cell membranes or translocating into cells through endocytosis and inducing cell apoptosis. Moreover, PTP-7z can also inhibit cancer cell migration. These results proved that HS-responsive in situ self-assembling is a practical strategy to overcome the cancer cell glycocalyx barrier for ACLPs and could be extended to the design of other peptide drugs to promote their in vivo application.
Source: openalex_inverted_index · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Glycosylation and Glycoproteins Research · Proteoglycans and glycosaminoglycans research · Peptidase Inhibition and Analysis

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China

Institute of Medical Science, China-Japan Friendship Hospital, Beijing 100029, China

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing 100142, China

Department of Chemistry, Chemical Biology, and Biomedical Engineering, Stevens Institute of Technology, Hoboken, New Jersey 07030, United States

Funding

National Key Research and Development Program of China · China Postdoctoral Science Foundation · China-Japan Friendship Hospital · Beijing University of Chemical Technology · Natural Science Foundation of Beijing Municipality · Fundamental Research Funds for the Central Universities · National Natural Science Foundation of China · Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing

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