Postpolymerization Modification of Poly(2-vinyl-4,4-dimethyl azlactone) as a Versatile Strategy for Drug Conjugation and Stimuli-Responsive Release
Biomacromolecules. 2024 Mar 8. doi: 10.1021/acs.biomac.4c00181. Online ahead of print.ABSTRACTPostpolymerization modification of highly defined "scaffold" polymers is a promising approach for overcoming the existing limitations of controlled radical polymerization such as batch-to-batch inconsistencies, accessibility to different monomers, and compatibility with harsh synthesis conditions. Using multiple physicochemical characterization techniques, we demonstrate that poly(2-vinyl-4,4-dimethyl azlactone) (PVDMA) scaffolds can be efficiently modified with a coumarin derivative, doxorubicin, and camptothecin small molecule drugs. Subsequently, we show that coumarin-modified PVDMA has a high cellular biocompatibility and that coumarin derivatives are liberated from the polymer in the intracellular environment for cytosolic accumulation. In addition, we report the pharmacokinetics, biodistribution, and antitumor efficacy of a PVDMA-based polymer for the first time, demonstrating unique accumulation patterns based on the administration route (i.e., intravenous vs oral), efficient tumor uptake, and tumor growth inhibition in 4T1 orthotopic triple negative breast cancer (TNBC) xenografts. This work establishes the utility of PVDMA as a versatile chemical platform for producing polymer-drug conjugates with a tunable, stimuli-responsive delivery.PMID:38457653 | DOI:10.1021/acs.biomac.4c00181
Source: Biomacromolecules - Category: Biochemistry Authors: Sk Arif Mohammad Veeresh B Toragall Alex Fortenberry Oluwaseyi Shofolawe-Bakare Suresh Sulochana Katie Heath Iyanuoluwani Owolabi Garrett Tassin Alex S Flynt Adam E Smith Thomas Werfel Source Type: research
More News: Biochemistry | Breast Cancer | Cancer | Cancer & Oncology | Chemistry | Environmental Health | Oral Cancer