Sung-Gun Kim

pH-responsive high-density lipoprotein-like nanoparticles to release paclitaxel at acidic pH in cancer chemotherapy

Background Nanoparticles undergoing physicochemical changes to release enclosed drugs at acidic pH conditions are promising vehicles for antitumor drug delivery. Among the various drug carriers, high-density lipoprotein (HDL)-like nanoparticles have been shown to be beneficial for cancer chemotherapy, but have not yet been designed to be pH-responsive. Methods and results In this study, we developed a pH-responsive HDL-like nanoparticle that selectively releases paclitaxel, a model antitumor drug, at acidic pH. While the well known HDL-like nanoparticle containing phospholipids, phosphatidylcholine, and apolipoprotein A-I, as well as paclitaxel (PTX-PL-NP) was structurally robust at a wide range of pH values (3.8–10.0), the paclitaxel nanoparticle that only contained paclitaxel and apoA-I selectively released paclitaxel into the medium at low pH. The paclitaxel nanoparticle was stable at physiological and basic pH values, and over a wide range of temperatures, which is a required feature for efficient cancer chemotherapy. The homogeneous assembly enabled high paclitaxel loading per nanoparticle, which was 62.2% (w/w). The molar ratio of apolipoprotein A-I and paclitaxel was 1:55, suggesting that a single nanoparticle contained approximately 110 paclitaxel particles in a spherical structure with a 9.2 nm diameter. Among the several reconstitution methods applied, simple dilution following sonication enhanced the reconstitution yield of soluble paclitaxel nanoparticles, which was 0.66. As a result of the pH responsiveness, the anticancer effect of paclitaxel nanoparticles was much more potent than free paclitaxel or PTX-PL-NP. Conclusion The anticancer efficacy of both paclitaxel nanoparticles and PTX-PL-NP was dependent on the expression of scavenger receptor class B type I, while the killing efficacy of free paclitaxel was independent of this receptor. We speculate that the pH responsiveness of paclitaxel nanoparticles enabled efficient endosomal escape of paclitaxel before lysosomal break down. This is the first report on pH-responsive nanoparticles that do not contain any synthetic polymer.

Comparison of xylitol production in recombinant Saccharomyces cerevisiae strains harboring XYL1 gene of Pichia stipitis and GRE3 gene of S. cerevisiae

Abstract Xylose reductase gene of Pichia stipitis ( XYL1 ) and aldose reductase of Saccharomyces cerevisiae ( GRE3 ) were expressed in S. cerevisiae to explore the xylitol production patterns in batch and fed-batch cultures. Although glucose utilization and ethanol formation of the two recombinant strains were not different in batch cultures, the xylitol productivity of the strain containing the S. cerevisiae GRE3 gene was 50% of that of the strain harboring the XYL1 gene of P. stipitis . Such a difference in xylitol productivity was confirmed in fed-batch cultures using ethanol as a cosubstrate for regeneration of NAD(P)H. S. cerevisiae GRE3 gene product showed a strong preference to NADPH, while the degrees of cofactor specificity of P. stipitis gene for both NADPH and NADH were almost identical. Similar amounts of xylose reductase were expressed in both recombinant strains, but a strict preference to NADPH in the S. cerevisiae with the GRE3 gene limited cofactor availability for xylose conversion and concomitantly resulted in lower xylitol productivity compared with the recombinant strain containing the P. stipitis XYL1 gene whose product exhibited almost the same cofactor specificity to NADPH and NADH.