دورية أكاديمية
أعرض في EDS

Protein-Polymer Conjugates Synthesized Using Water-Soluble Azlactone-Functionalized Polymers Enable Receptor-Specific Cellular Uptake toward Targeted Drug Delivery.

التفاصيل البيبلوغرافية
العنوان: Protein-Polymer Conjugates Synthesized Using Water-Soluble Azlactone-Functionalized Polymers Enable Receptor-Specific Cellular Uptake toward Targeted Drug Delivery.
المؤلفون: Kim JS, Sirois AR; Molecular and Cellular Biology Program , University of Massachusetts Amherst , Amherst , Massachusetts 01003 , United States., Vazquez Cegla AJ, Jumai'an E, Murata N, Buck ME, Moore SJ
المصدر: Bioconjugate chemistry [Bioconjug Chem] 2019 Apr 17; Vol. 30 (4), pp. 1220-1231. Date of Electronic Publication: 2019 Apr 05.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 9010319 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4812 (Electronic) Linking ISSN: 10431802 NLM ISO Abbreviation: Bioconjug Chem Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Chemical Society, c1990-
مواضيع طبية MeSH: Drug Delivery Systems*, Lactones/*chemistry , Polymers/*chemistry , Proteins/*chemistry , Receptors, Transferrin/*metabolism, Cell Line, Tumor ; Chromatography, Gel ; Endocytosis ; Humans ; Solubility ; Water/chemistry
مستخلص: Conjugation of proteins to drug-loaded polymeric structures is an attractive strategy for facilitating target-specific drug delivery for a variety of clinical needs. Polymers currently available for conjugation to proteins generally have limited chemical versatility for subsequent drug loading. Many polymers that do have chemical functionality useful for drug loading are often insoluble in water, making it difficult to synthesize functional protein-polymer conjugates for targeted drug delivery. In this work, we demonstrate that reactive, azlactone-functionalized polymers can be grafted to proteins, conjugated to a small-molecule fluorophore, and subsequently internalized into cells in a receptor-specific manner. Poly(2-vinyl-4,4-dimethylazlactone), synthesized using reversible addition-fragmentation chain transfer polymerization, was modified post-polymerization with substoichiometric equivalents of triethylene glycol monomethyl ether to yield reactive water-soluble, azlactone-functionalized copolymers. These reactive polymers were then conjugated to proteins holo-transferrin and ovotransferrin. Protein gel analysis verified successful conjugation of proteins to polymer, and protein-polymer conjugates were subsequently purified from unreacted proteins and polymers using size exclusion chromatography. Internalization experiments using a breast cancer cell line that overexpresses the transferrin receptor on its surface showed that the holo-transferrin-polymer conjugate was successfully internalized by cells in a mechanism consistent with receptor-mediated endocytosis. Internalization of protein-polymer conjugate demonstrated that the protein ligand maintained its overall structure and function following conjugation to polymer. Our approach to protein-polymer conjugate synthesis offers a simple, tailorable strategy for preparing bioconjugates of interest for a broad range of biomedical applications.
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معلومات مُعتمدة: R15 CA198927 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Lactones)
0 (Polymers)
0 (Proteins)
0 (Receptors, Transferrin)
059QF0KO0R (Water)
تواريخ الأحداث: Date Created: 20190329 Date Completed: 20200217 Latest Revision: 20231012
رمز التحديث: 20231012
مُعرف محوري في PubMed: PMC6608588
DOI: 10.1021/acs.bioconjchem.9b00155
PMID: 30920802
قاعدة البيانات: MEDLINE
الوصف
تدمد:1520-4812
DOI:10.1021/acs.bioconjchem.9b00155