Folate Conjugation to Polymeric Micelles via Boronic
Acid Ester to Deliver Platinum Drugs to Ovarian Cancer Cell Lines
Wei Scarano
Hien T.
T. Duong
Hongxu Lu
Paul L. De Souza
Martina H. Stenzel
10.1021/bm400121q.s001
https://acs.figshare.com/articles/journal_contribution/Folate_Conjugation_to_Polymeric_Micelles_via_Boronic_Acid_Ester_to_Deliver_Platinum_Drugs_to_Ovarian_Cancer_Cell_Lines/2426179
In this study, a novel technique
was used for the reversible attachment
of folic acid on the surface of polymeric micelles for a tumor-specific
drug delivery system. The reversible conjugation is based on the interaction
between phenylboronic acid (PBA) and dopamine to form a borate ester.
The conjugation is fast and efficient and in vitro experiments via
confocal fluorescent microscopy show that the linker is stable in
for several hours. Reversible addition–fragmentation chain
transfer (RAFT) polymerization was used to synthesize two various
sized water-soluble block copolymer of oligoethylene glycol methylether
methacylate and methyl acrylic acid (POEGMEMA<sub>35</sub>-<i>b</i>-PMAA<sub>200</sub> and POEGMEMA<sub>26</sub>-<i>b</i>-PMAA<sub>90</sub>). The platinum drug, oxoplatin, was then subsequently
attached to the polymer via ester formation leading to platinum loading
of 12 wt % as determined by TGA. The platinum-induced amphiphilic
block copolymers that consequently led to the formation of micelles
of sizes 150 and 20 nm in an aqueous environment with the longer PMAA
block forming larger micelles. The small micelles were in addition
cross-linked using 1,8-diaminooctane to further stabilize their structure.
The targeting ability of folate conjugated polymeric micelles was
investigated against two types of tumor cell lines: A549 (-FR) and
OVCAR-3 (+FR). The cell line growth inhibitory efficacy of material
synthesized was evaluated by using SRB method. The results revealed
that folate conjugated micelles showed higher activity in FR + OVCAR-3
cells but not in FR – A549 cells. Similar results were obtained
for both small and large micelles without the conjugation of folate.
Comparing large and small micelles it can be observed that larger
micelles are more efficient, which has been attributed to the lower
stability of the smaller micelles. Micelle stabilization via cross-linking
could indeed increase the toxicity of the drug carrier.
2013-04-08 00:00:00
microscopy show
novel technique
methyl acrylic acid
POEGMEMA
ester formation
sizes 150
borate ester
20 nm
platinum drug
drug carrier
tumor cell lines
micelle
OVCAR
Ovarian Cancer Cell LinesIn
block copolymer
PBA
folic acid
FR
PMAA block
Folate Conjugation
Platinum Drugs
oligoethylene glycol methylether methacylate
platinum loading
Polymeric Micelles
phenylboronic acid
cell line growth
SRB method
549 cells
Similar results
TGA
Micelle stabilization