title: Acid-sensitive dextran prodrug: A higher molecular weight makes a better efficacy.
abstract: The acid-sensitive polymer prodrugs have attracted increasing attention because of their selective intratumoral or intracellular drug release. Herein, two intracellular acid-sensitive dextran-doxorubicin (Dex-DOX) conjugates with similar drug binding rate were synthesized through the Schiff base reaction between the aldehyde group in the oxidized Dex with different lengths and the amino group of DOX. The amphiphilic Dex-DOX conjugates self-assembled into micellar nanoparticles in phosphate-buffered saline (PBS). The micelle of prodrug with longer Dex, that is, Dex500k-DOX, exhibited smaller size, quicker drug release, higher cell internalization, and stronger tumor suppression with upregulated security in comparison with the one with shorter Dex, that is, Dex40k-DOX. Therefore, the molecular weight of prodrug backbone could adjust the properties, and a higher molecular weight endowed the Dex-DOX conjugate with a better antitumor efficacy in a limited number of tested samples.
authors.affiliation: Department of Chemistry, Northeast Normal University, Changchun 130024, PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Li
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Han
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China. Electronic address: jxding@ciac.ac.cn.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Chemistry, Northeast Normal University, Changchun 130024, PR China. Electronic address: chenl686@nenu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003911:Dextrans / Q000138:chemical synthesis / Q000737:chemistry*; D004317:Doxorubicin; D006801:Humans; D008823:Micelles; D008970:Molecular Weight; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D003911:Dextrans; D008823:Micelles; D011355:Prodrugs; D004317:Doxorubicin
keywords: Acid-sensitivity; Chemotherapy; Molecular weight; Prodrug; Synergy and attenuation