“…3J , the apoptosis rate of HepG2 was 43.0% and 52.3%, and that of MCF-7 was 36.1% and 60.2% induced by CLB and OE-CLB-NPs, respectively. The result was similar with that of cytotoxicity and suggested that apoptosis promoted cytotoxicity [ 38 , 39 ]. Fig.…”
“…3J , the apoptosis rate of HepG2 was 43.0% and 52.3%, and that of MCF-7 was 36.1% and 60.2% induced by CLB and OE-CLB-NPs, respectively. The result was similar with that of cytotoxicity and suggested that apoptosis promoted cytotoxicity [ 38 , 39 ]. Fig.…”
“…In addition, their morphology and average diameters observed by TEM were spherical and smaller due to shrinkage in a dry state . These superior characteristics were beneficial to stable blood circulation by escaping the reticuloendothelial system (RES) and promoting the tumor formation via the enhanced permeability and retention (EPR) effect. , As shown in Figure g, on one hand, the particle sizes of NPs remained the same at physiological pH (7.4) in 120 h, implying their long-term storage stability . On the other hand, the particle sizes of NP2 gradually decreased from 176.2 to 128.9 nm at tumoral intracellular pH (5.0) in 120 h owing to the degradation of ortho ester linkages following the time course (Figures S8 and S9), possibly facilitating tumoral intracellular efficient drug release .…”
Section: Resultsmentioning
confidence: 89%
“…28,29 As shown in Figure 1g, on one hand, the particle sizes of NPs remained the same at physiological pH (7.4) in 120 h, implying their longterm storage stability. 30 On the other hand, the particle sizes of NP2 gradually decreased from 176.2 to 128.9 nm at tumoral intracellular pH (5.0) in 120 h owing to the degradation of ortho ester linkages following the time course (Figures S8 and S9), possibly facilitating tumoral intracellular efficient drug release. 31 However, the particle sizes of NP1 were still maintained the same at pH 5.0 in 120 h. Notably, the particle size alone cannot determine the amount of drug release.…”
Section: Synthesis and Characterization Of 5fu Prodrugmentioning
5-Fluorouracil (5FU) and its derivatives have been widely used for cancer treatment; however they fail to achieve selective chemotherapy. Herein, this work highlights a successful development of a pH-sensitive aliphatic 5fluorouracil (5FU) derivative prodrug, which is synthesized via chemically linking 5FU and stearyl alcohol (SA) using ortho ester linkage. It can further selfassemble into a synergistic small molecule nanodrug through a noncovalent interaction with doxorubicin (DOX). The nanodrug displays precise structure and high drug loading (more than 15% of drug loading content (DLC) and 87% of drug loading efficiency (DLE)). SA and ortho ester linkages endow the nanodrug with high lipophilicity on tumor cell membrane and tumoral intracellular pH response, respectively. The nanodrug also exhibits a slightly negatively charged surface (−0.513 mV) at physiological pH (7.4) and a large-to-small size change from 176.2 to 128.9 nm at tumoral intracellular pH (5.0). These superior characteristics endow the nanodrugs with blood circulation stability, selective tumor accumulation, improved cellular uptake, efficient drug release, as well as synergistic effect on tumor cells, thereby significantly inhibiting tumor growth (smaller than initial tumor size), reducing side effects, and prolonging survival time. Thus, such a pH-sensitive small molecule nanodrug self-assembled from the aliphatic 5FU derivative and DOX has a great potential for selective synergistic cancer therapy, greatly advancing their clinical use.
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