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. 2018 Dec 3;13:8231–8245. doi: 10.2147/IJN.S174300

Figure 4.

Figure 4

MPEG-PLA nanoparticles encapsulated CQ and DOX enhanced cell apoptosis in vitro and drug accumulation in tumor sites in vivo.

Notes: (A) Size distribution spectrum of DOX- and CQ-loaded MPEG-PLA nanoparticles was examined. (B) TEM image of DOX- and CQ-loaded MPEG-PLA nanoparticles was shown (Scale bar, 40 nm). (C) Zeta potential spectrum of DOX- and CQ-loaded MPEG-PLA micelles. (D) Drug release of free DOX and DOX-CQ/PP under different pH conditions (pH 5.5 and pH 7.4) (n=3). (E) Drug release of free CQ and DOX-CQ/PP under different pH conditions (pH 5.5 and pH 7.4) (n=3). (F) The EE and DL of CQ/DOX/DDP/PTX encapsulated by MPEG-PLA were examined. (G) A2780 cells were treated with DOX (1 µM), DOX/PP (DOX concentration 1 µM) and DOX-CQ/PP for 4 hours. The drug uptake was detected by concofol. (H) A2780 cells were treated with DOX (1 µM), MPEG-PLA encapsulated DOX (DOX concentration 1 µM) with or without CQ (10 µM). The MFI of the A2780 treated with DOX (1 µM), MPEG-PLA encapsulated DOX (DOX concentration 1 µM) with or without CQ (10 µM) was detected by flow cytometry at different time points. (I) The cell viability of A2780 cells treated with PBS, DOX (0.1 µM), DOX/PP (DOX concentration 0.1 µM), and DOX-CQ/PP (DOX concentration 0.1 µM and CQ concentration 10 µM) for 48 hours. (J) The cell viability of A2780 cells treated with PBS, DDP (20 µM), DDP/PP (DDP concentration 20 µM) and DDP-CQ/PP (DDP concentration 20 µM and CQ concentration 10 µM). (K) The cell viability of A2780 cells treated with PBS, PTX (4 µM), PTX/PP (PTX concentration 4 µM) and PTX-CQ/PP (PTX concentration 4 µM and CQ concentration 10 µM) for 48 hours. (L) The cell viability of A2780/DOXR cells treated with PBS, DOX (0.1 µM), DOX/PP (DOX concentration 0.1 µM) and DOX-CQ/PP (DOX concentration 0.1 µM and CQ concentration 10 µM) for 48 hours. (M) Nude mice bearing A2780 cells treated with DOX (5 mg/kg), DOX/PP (DOX concentration 5 mg/kg) and DOX-CQ/PP (DOX concentration 5 mg/kg, CQ concentration 5 mg/kg) every 2 days for 10 days, then sacrificed the mice and obtained blood, tumor tissue and organs. HPLC was used to detect the concentration of DOX (n=6). PP was short for MPEG-PLA. *P<0.05; **P<0.01; ***P<0.001.

Abbreviations: CQ, chloroquine; DL, drug loading; DOX, doxorubicin; EE, encapsulation efficiency; MFI, mean fluorescence intensity; MPEG-PLA, methoxy poly(ethylene glycol)-poly(l-lactic acid); ns, not statistically significant; TEM, transmission electron microscope.