Amphiphilic Cationic Peptide-Coated PHA Nanosphere as an Efficient Vector for Multiple-Drug Delivery

Abstract

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.

Biomaterials-mediated CRISPR/Cas9 delivery: recent challenges and opportunities in gene therapy

“…The researchers successfully carried CRISPR/Cas9 plasmids to target cells and started gene editing in a mouse model using PHA nanoparticles. In addition to being studied as a delivery method for CRISPR-Cas systems, PHAs are also being investigated as a scaffold material for those systems ( Zhang et al, 2022 ). In a different study, scientists demonstrated how to use a scaffold made of PHA and CRISPR/Cas9 plasmids to treat bone defects.…”

Synthesis, Properties and Applications of Polymeric Nanomaterials

“…This Special Issue, focused on polymeric nanomaterials, reports the latest advances in the synthesis, properties, and applications of this useful and versatile class of nanocomposites. These compounds can be used in drug delivery for the treatment of cancer cells, providing a platform for the co-delivery of nucleic acids and hydrophobic drugs [1]. Another area where such nanopolymers can fruitfully be applied is bone regeneration for maxillofacial reconstructive surgery; new nanomaterials based on hydroxyapatite and poly-l-lactide acid have been shown to be able to recover critical defects in rat mandibles [2], paving the way to their use in humans.…”