Amphiphilic core–shell (ACS) nanoparticles are gaining increasing research interest for multi-drug delivery in cancer therapy. In this work, a new cationic peptide-coated PHA nanosphere was prepared by self-assembly of a hydrophobic core of biodegradable poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and a hydrophilic shell of fusion proteins of PHA granule-associated protein (PhaP) and cationic peptide RALA through a strong hydrophobic effect. The hydrophobic drug curcumin (Cur) was encapsulated in PHBHHx nanoparticles. The chemotherapy drug 5-fluorouracil (5-FU) was administered in the form of its metabolite oligomeric 5-fluorodeoxyuridine (FUdR). Fifteen consecutive FUdR (FUdR15S) were adsorbed on the surface of PHBHHx nanoparticles by electrostatic interaction with RALA to form Cur@PHBX-PR/FUdR15S. Such amphiphilic cationic nanospheres had 88.3% EE of Cur and the drug loading of Cur and FUdR were 7.8% and 12.1%. The dual-drug-loaded nanospheres showed a time-differential release of Cur and FUdR. In addition, Cur@PHBX-PR/FUdR15S exhibited excellent anticancer activity and played a vital role in promoting the synergistic effect of FUdR and Cur in gastric cancer cells. The exploration of antitumor mechanisms demonstrated that Cur improved the activity of apoptosis-related proteins and cancer cells sensitized to FUdR. This amphiphilic core–shell system can serve as a general platform for sequential delivery of multiple drugs to treat several cancer cells.
Polyhydroxyalkanoates (PHA) produced by Bacillus bacteria have potential advantages in medical applications, due to its cell membrane do not contain outer membrane lipopolysaccharide (LPS). However, the PHA accumulation level is far lower than that of Gram-negative bacteria. In this study, an alkali-tolerant Bacillus cereus HBL-AI was screened using Nile Red and Sudan Black B in a Low-Salt LB solid medium at pH 8.0. This strain displayed high PHA accumulation capacity in fed‑batch fermentation with glucose as the carbon source in a 5 L unsterilized fermentor. The highest PHA accumulation reached 12.8 g/L and the extracted product was finally determined as (Poly-β-3-hydroxybutyrate, PHB). It has the potential to be used for large-scale open and continuous fermentation. Furthermore, PHA membrane binding protein (PhaP), PHA regulatory protein (PhaQ and PhaR) derived from HBL-AI were heterologously expressed inE. coli and purified to investigate their application as biosurfactants. The results showed that the emulsification ability and stability of three amphiphilic proteins were higher than those of widely used chemical surfactants. The protein concentration of PhaQ used to form a stable emulsion layer in vegetable oil was the lowest (50 μg/mL), which greatly reduced the amount of protein used in emulsification. This clearly demonstrated that HBL-AI has great potential in the production of PHA without endotoxin, and its PHA binding protein can be well applied as an environmentally friendly biosurfactants.
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