Poly(l-lysine)-graft-folic acid-coupled poly(2-methyl-2-oxazoline) (PLL-g-PMOXA-c-FA): A Bioactive Copolymer for Specific Targeting to Folate Receptor-Positive Cancer Cells

Abstract

In this study, we present the preparation, characterization and application of a novel bioactive copolymer poly(l-lysine)-graft-folic acid-coupled poly(2-methyl-2-oxazoline) (PLL-g-PMOXA-c-FA), which has a specific interaction with folate receptor (FR)-positive cancer cells. Glass surface immobilized with PLL-g-PMOXA-c-FA was demonstrated to be adhesive to FR-positive cancer cells (HeLa, JEG-3) while nonadhesive to FR-negative ones (MCF-7, HepG2) in 3 h. The specific interaction between conjugated FA on the substrate and FRs on the cells could hardly be inhibited unless a high concentration (5 mM) of free FA was used due to the multivalent nature of it. The FA functionality ratio of the copolymer on the substrate had a significant influence on the adhesion of HeLa cells, and our experiments revealed that the affinity of the substrate to the cells declined dramatically with the decrease of functionality ratio. This was believed to be caused by the polydispersity of PMOXA tethers, as supported by GPC and ToF-SIMS data. As a proof of concept in the application of our material, we demonstrated successful recovery of HeLa cells from mixture with MCF-7 (1:100) on the copolymer-coated glass, and our results showed that both high sensitivity (95.6 ± 13.3%) and specificity (24.3 ± 8.6%) were achieved.

Multi‐Functional Peptide–MicroRNA Nanocomplex for Targeted MicroRNA Delivery and Function Imaging

“…The nanocomplex-mediated miRNA delivery efficiency into different cell lines was then comparedtoconfirm the target-selectivity.A ccording to previous report, HepG2, MCF-7 and A549 cells did not express high level of FR compared with HeLa cells or KB cells. [14] We comparedt he relative FR level in these cell lines ( Figure S4), which showedt hat HeLa cells and KB cells have much higher level of FR compared with HepG2, MCF-7 and A549 cells. Then the nanocomplex-mediated miR-34a delivery efficiency wast ested on these cell lines to confirm that the nanocomplex MIRNC-34a was ablet od istinguish FR positive cellsf rom FR negative cells.…”

Multifunctional streptavidin–biotin conjugates with precise stoichiometries

“…For instance, we added folic acid, an active and selective targeting molecule for aggressive cancer cells that overexpress the folic acid receptor on their surfaces. [19][20][21] The folic acid and atto-565 labelled streptavidins allowed us to determine whether the number of folic acid groups per molecule impacts cellular uptake by using the signal from the uorescent label. For this purpose, pure SA 3 , SA 2 and SA 1 were each incubated rst with excess folic acid-PEG-biotin (F) for 20 minutes and then excess F was removed by dialysis.…”

Thioacetate‐Based Initiators for the Synthesis of Thiol‐End‐Functionalized Poly(2‐oxazoline)s

“…This method has been rather parsimoniously used in the synthesis of α‐functional PAOx. Example of protecting groups incorporated in cROP initiators include N ‐alkylphthalimide or tert ‐butyl N ‐monoalkylcarbamate (for amines), [ 52–56 ] tert‐ butyldiphenylsilyl ethers (for hydroxyl), [ 57 ] methyl ester (for carboxylic acid or others through amidation), [ 58–63 ] and furanyl Diels–Alder cycloadduct (for maleimide). [ 64 ] Here, the thioacetate group has been chosen as a stable and economic protection group for thiols.…”