bm201478k_si_003.pdf (851.01 kB)
Norbornene Derived Doxorubicin Copolymers as Drug Carriers with pH Responsive Hydrazone Linker
journal contribution
posted on 2012-01-09, 00:00 authored by Vijayakameswara Rao N, Shivshankar R. Mane, Abhinoy Kishore, Jayasri Das Sarma, Raja ShunmugamThe synthesis and complete characterization of both norbornene-derived
doxorubicin (mono 1) and polyethylene glycol (mono 2) monomers are clearly described, and their copolymerization
by ring-opening metathesis polymerization (ROMP) to get the block
copolymer (COPY-DOX) is vividly elaborated. The careful
design of these conjugates exhibits properties like well-shielded
drug moieties and well-defined nanostructures; additionally, they
show solubility in both water and biological medium and also have
the important tendency of rendering acid-triggered drug release. The
drug release profile suggests the importance of having the hydrazone
linker that helps to release the drug exactly at the mild acidic conditions
resembling the pH of the cancerous cells. It is also observed that
the drug release from micelles of COPY-DOX is significantly
accelerated at a mildly acidic pH of 5.5–6, compared to the
physiological pH of 7.4, suggesting the pH-responsive feature of the
drug delivery system with hydrazone linkages. Confocal laser scanning
microscopy (CLSM) measurements indicate that these COPY-DOX micelles are easily internalized by living cells. MTT assays against
HeLa and 4T cancer cells showing COPY-DOX micelles have
a high anticancer efficacy. All of these results demonstrate that
these polymeric micelles that self-assembled from COPY-DOX block copolymers have great scope in the world of medicine, and
they also symbolize promising carriers for the pH-triggered intracellular
delivery of hydrophobic anticancer drugs.
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pH Responsive Hydrazone LinkerThe synthesis4 T cancer cellsacidic conditionsMTT assaysdrug releasehydrazone linkagesmicelleDrug Carriersblock copolymershow solubilityanticancer drugsconjugates exhibits propertiesNorbornene Derived Doxorubicin CopolymersROMPCLSMdrug delivery systemanticancer efficacypolyethylene glycolConfocal laser scanning microscopyhydrazone linkerdrug release profileacidic pH
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