Abstract
Numerous nanocarriers with excellent biocompatibilities have been used to improve cancer therapy. However, nonspecific protein adsorption of nanocarriers may block the modified nanoparticles in tumor cells, which would lead to inefficient cellular internalization. To address this issue, pH-responsive polyurethane prodrug micelles with a zwitterionic segment were designed and prepared. The micelle consisted of a zwitterionic segment as the hydrophilic shell and the drug Adriamycin (DOX) as the hydrophobic inner core. As a pH-responsive antitumor drug delivery system, the prodrug micelles showed high stability in a physiological environment and continuously released the drug under acidic conditions. In addition, the pure polyurethane carrier was demonstrated to be virtually non-cytotoxic by cytotoxicity studies, while the prodrug micelles were more efficient in killing tumor cells compared to PEG-PLGA@DOX. Furthermore, the DOX cellular uptake efficiency of prodrug micelles was proved to be obviously higher than the control group by both flow cytometry and fluorescence microscopy. This is mainly due to the modification of a zwitterionic segment with PU. The simple design of zwitterionic prodrug micelles provides a new strategy for designing novel antitumor drug delivery systems with enhanced cellular uptake rates.
Highlights
Nowadays, the topic of health has attracted a lot of attention
The results showed that the prodrug micelles remain relatively stable in the normal human physiological environment and showed a rapid response to release in an acidic environment, i.e., at the tumor site
Fluorescence microscopy further cysutopmpeotrryte(dFitghuirsev5i)eswho. wed that PEG-PLGA@DOX was consistently lower than the cellular uptake rate of the prodrug micelles
Summary
The topic of health has attracted a lot of attention. As reported by the World Health Organization (WHO), cancer kills nearly 18 million people per year and has become a major threat to human health [1]. Most conventional chemotherapeutic agents (e.g., Adriamycin (DOX), methotrexate, and camptothecin) have serious disadvantages that need to be addressed, such as low selectivity, low water solubility, substantial side effects, and short circulation time in the body [2,3] To overcome these problems, scientists have developed a range of nanocarriers, such as nanoparticles, liposomes, nanogels and micelles through nanotechnology [4–8], such as nanocarrier-based polymer prodrugs. 222...444...CCCeeellllluuulllaaarrrUUUppptttaaakkkeee TTTooo ssstttuuudddyyy ttthhheee mmmeeeccchhhaaannniiisssmmmooofff eeennnhhhaaannnccceeedddcccyyytttoootttoooxxxiiiccciiitttyyyooofffttthhheeepppooolllyyymmmeeerrrppprrrooodddrrruuugggmmmiiiccceeellllleeesss,,, ttthhheeeccceeellllluulullaalarr ruuupppttaatkkaeekeooffoPPf EEPGGE--GPP-LLPGGLAAG@@ADD@OODXXOaaXnnddanPPdUUP--hhUyy-ddh--yDDdOO-DXXOmmXiiccmeellllieecsselaalttesddiiaffffteedrreeifnnfttertteiimmnteesstiwwmaaesss sswttuuaddsiieestdduduuisseiinndggubbsoointthhg bffllootwwh flccyyottwoommcyeettrroyymaaenntrddyffalluunoodrreeflssucceeonnreccseecmmeniiccerroomssccioocpproyys..cTTohhpeey.rreeTsshuuellttrsseffsrruoolmmts ffrlloowwm flow cytometry (Figure 5) showed that PEG-PLGA@DOX was consistently lower than the cellular uptake rate of the prodrug micelles. Wed that PEG-PLGA@DOX was consistently lower than the cellular uptake rate of the prodrug micelles. PU-hyd-DOX micelles were suspended in a dialysis bag (MWCO = 3.5 kDa) at different buffer solutions (pH = 7.4 or 5.0) with continuous stirring at 37 ◦C. Every experiment was conducted three times, and the results in this work are presented as the mean ± standard deviation (SD)
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