Multifunctional PEG Carrier by Chemoenzymatic Synthesis for Drug Delivery Systems: In Memory of Professor Andrzej Dworak.
Judit E PuskasGayatri ShrikhandeEniko KrischKristof MolnarPublished in: Polymers (2022)
This paper describes the synthesis and characterization of new bivalent folate-targeted PEGylated doxorubicin (FA 2 -dPEG-DOX 2 ) made by modular chemo-enzymatic processes using Candida antarctica lipase B (CALB) as a biocatalyst. Unique features are the use of monodisperse PEG (dPEG) and the synthesis of thiol-functionalized folic acid yielding exclusive γ-conjugation of folic acid (FA) to dPEG. The polymer-based drug conjugate is built up by a series of transesterification and Michael addition reactions all catalyzed be CALB. In comparison with other methods in the literature, the modular approach with enzyme catalysis leads to selectivity, full conversion and high yield, and no transition metal catalyst residues. The intermediate product with four acrylate groups is an excellent platform for Michael-addition-type reactions for a wide variety of biologically active molecules. The chemical structures were confirmed by nuclear magnetic resonance spectroscopy (NMR). Flow cytometry analysis showed that, at 10 µM concentration, both free DOX and FA 2 -dPEG-DOX 2 were taken up by 99.9% of triple-negative breast cancer cells in 2 h. Fluorescence was detected for 5 days after injecting compound IV into mice. Preliminary results showed that intra-tumoral injection seemed to delay tumor growth more than intravenous delivery.
Keyphrases
- cancer therapy
- drug delivery
- flow cytometry
- transition metal
- breast cancer cells
- room temperature
- high resolution
- systematic review
- magnetic resonance
- single molecule
- photodynamic therapy
- candida albicans
- quantum dots
- hydrogen peroxide
- high dose
- type diabetes
- metal organic framework
- ionic liquid
- low dose
- visible light
- squamous cell carcinoma
- reduced graphene oxide
- adverse drug
- highly efficient
- nitric oxide
- insulin resistance
- radiation therapy
- metabolic syndrome
- escherichia coli
- drug induced
- gold nanoparticles
- molecularly imprinted
- electronic health record
- single cell
- structural basis