Folate-Targeted Monodisperse PEG-Based Conjugates Made by Chemo-Enzymatic Methods for Cancer Diagnosis and Treatment

Abstract

This paper focuses on preliminary in vitro and in vivo testing of new bivalent folate-targeted PEGylated doxorubicin (DOX) made by modular chemo-enzymatic processes (FA2-dPEG-DOX2). A unique feature is the use of monodisperse PEG (dPEG). The modular approach with enzyme catalysis ensures exclusive γ-conjugation of folic acid, full conversion and selectivity, and no metal catalyst residues. Flow cytometry analysis showed that at 10 µM concentration, both free DOX and FA2-dPEG-DOX2 would be taken up by 99.9% of triple-negative breast cancer cells in 2 h. Intratumoral injection to mice seemed to delay tumor growth more than intravenous delivery. The mouse health status, food, water consumption, and behavior remained unchanged during the observation.

Multifunctional PEG Carrier by Chemoenzymatic Synthesis for Drug Delivery Systems: In Memory of Professor Andrzej Dworak

“…FA 2 -dPEG 20 -DOX 2 was tested in vitro and in vivo in comparison with free DOX at the same concentration [ 22 , 23 ]. Free DOX already showed a cytotoxic effect after 24 h at 0.1 μM concentration, while no toxicity was observed with FA 2 -dPEG-DOX 2 .…”

“…The slight autofluorescence, as seen in ( a ) before injection, is clearly different from the fluorescent signals of injected animals. Reproduced with permission from [ 23 ]. 2022, MDPI.…”

“…The authors acknowledge the Ohio State University USDA-NIFA under Hatch project number OHO01417 and the Breast Cancer Innovation Foundation for financial support. Reproduced with permission from [23]. 2022, MDPI.…”

“…Therefore, we designed a new PDC platform based on a four-functional dPEG core to which drug and diagnostic molecules could be attached via enzyme-catalyzed Michael addition. The first compound tested was a bivalent folate-targeted PEGylated doxorubicin (DOX) serving as both a drug and an imaging agent, made by modular chemo-enzymatic processes (FA 2 -dPEG-DOX 2 ) [ 23 ]. DOX is a widely used chemotherapeutic drug, which prohibits cell division by blocking the topoisomerase 2 enzyme [ 24 ].…”

Conjugation of Palbociclib with MHI-148 Has an Increased Cytotoxic Effect for Breast Cancer Cells and an Altered Mechanism of Action

“…Other conjugated compounds, such as folate-targeted PEGylated doxorubicin, have been compared with free doxorubicin for targeting efficiency, since doxorubicin itself has intrinsic fluorescence [ 29 ]. However, the targeting efficiency of free palbociclib and MHI-palbociclib was not measured because the detection of MHI-palbociclib (detected using filter of 570–700 nm) cannot detect free palbociclib for comparison.…”