首页|Intelligent micro-vehicles for drug transport and controlled release to cancer cells
Intelligent micro-vehicles for drug transport and controlled release to cancer cells
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NETL
NSTL
Elsevier
The idea that pH decreases significantly in tumors is widespread, however recent progress in the measurement of pH in cancer tissues has revealed that the intracellular pH of cancer cells is neutral or even mildly alkaline compared to normal tissues [Hao et al., 2018]. However, in both cancer and normal cells the pH drops from 6.0-5.5 in endosomes to 5.0 in lysosomes after particle internalization by EPR effect. Here, the design of "intelligent" delivery systems able to exploit these pH variations is reported. Poly(N-isopropylacrylamide-co-4-vinylpyridine) (poly(NIPAAm-co-4-VP)) was synthesized and characterized as an exciting pH/temperature sensitive copolymer with a pKa value of 5.05. The lower critical solution temperature (LCST) of the copolymer was determined at physiological conditions (phosphate buffer (PB) at pH = 7.4 and 36 degrees C), and at acidic pH values similarly to those of cell compartments. Values of LCST of the copolymer with the co-monomer molar ratio of 86:14 (NIPAAm:4-VP) are 22.1 and 36.8 degrees C in PB at pH = 7.4 and pH = 5.0, respectively. Therefore, the drug loaded microspheres synthesized from this copolymer are insoluble at physiological conditions and keep the drug inside, but quickly solubilize at lysosomal conditions (pH = 5.0) releasing the cargo.
NETL
NSTL
Elsevier
