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Polyamine-Responsive Morphological Transformation of a Supramolecular Peptide for Specific Drug Accumulation and Retention in Cancer Cells
Sun, Chen1; Wang, Ziyi1; Yang, Kuikun1; Yue, Ludan1; Cheng, Qian1; Ma, Yan long1; Lu, Siyu2; Chen, Guosong3; Wang, Ruibing1
2021-10-27
Source PublicationSmall
ISSN1613-6810
Volume17Issue:43
Abstract

The precise accumulation and extended retention of nanomedicines in the tumor tissue has been highly desired for cancer therapy. Here a novel supramolecular-peptide derived nanodrug (SPN) that can be transformed to microfibers in response to intracellular polyamine in cancer cells for significantly enhanced tumor specific accumulation and retention is developed. The supramolecular-peptide is constructed via the non-covalent interactions between cucurbit[7]uril (CB[7]) and Phe on Phe-Phe-Val-Leu-Lys-camptothecin conjugates (FFVLK-CPT, PC). The resultant amphiphilic supramolecular complex subsequently self-assembles into nanoparticles with a hydrodynamic diameter of 164.2 ± 3.7 nm. Upon internalization into spermine-overexpressed cancer cells, the CB[7]-Phe host–guest pairs can be competitively dissociated by spermine and can release free PC, which immediately form β-sheet structures and subsequently reorganize into microfibers, leading to dramatically improved accumulation, retention, and sustained release of CPT in tumor cells for highly effective cancer therapy. Accordingly, this SPN exhibit rather low toxicity against non-cancerous cells due to the morphological stability and fast exocytosis of the nanodrugs in those cells without abundant spermine. This study reports the first supramolecular peptide capable of polyamine-responsive “nanoparticle-to-microfiber” transformation for specific tumor therapy with minimal side effects. This work also offers novel insights to the design and development of stimuli-responsive nanomaterials as precision medicine.

KeywordCucurbituril Morphology Transformation Polyamine-responsive Self-assembly Supramolecular-peptide
DOI10.1002/smll.202101139
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaChemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
WOS SubjectChemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied ; Physics, Condensed Matter
WOS IDWOS:000659706400001
Scopus ID2-s2.0-85107512802
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Cited Times [WOS]:21   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionDEPARTMENT OF PHARMACEUTICAL SCIENCES
Institute of Chinese Medical Sciences
THE STATE KEY LABORATORY OF QUALITY RESEARCH IN CHINESE MEDICINE (UNIVERSITY OF MACAU)
Corresponding AuthorWang, Ruibing
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078, China
2.Green Catalysis Center, College of Chemistry, Zhengzhou University, Zhengzhou, 450001, China
3.State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, 200433, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Sun, Chen,Wang, Ziyi,Yang, Kuikun,et al. Polyamine-Responsive Morphological Transformation of a Supramolecular Peptide for Specific Drug Accumulation and Retention in Cancer Cells[J]. Small,2021,17(43).
APA Sun, Chen,Wang, Ziyi,Yang, Kuikun,Yue, Ludan,Cheng, Qian,Ma, Yan long,Lu, Siyu,Chen, Guosong,&Wang, Ruibing.(2021).Polyamine-Responsive Morphological Transformation of a Supramolecular Peptide for Specific Drug Accumulation and Retention in Cancer Cells.Small,17(43).
MLA Sun, Chen,et al."Polyamine-Responsive Morphological Transformation of a Supramolecular Peptide for Specific Drug Accumulation and Retention in Cancer Cells".Small 17.43(2021).
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