Development of Polymersomes Co-Delivering Doxorubicin and Melittin to Overcome Multidrug Resistance.
Eunkyung HanDoyeon KimYoungheun ChoSeonock LeeJungho KimHyuncheol KimPublished in: Molecules (Basel, Switzerland) (2023)
Multidrug resistance (MDR) is one of the major barriers in chemotherapy. It is often related to the overexpression of efflux receptors such as P-glycoprotein (P-gp). Overexpressed efflux receptors inhibit chemotherapeutic efficacy by pumping out intracellularly delivered anticancer drugs. In P-gp-mediated MDR-related pathways, PI3K/Akt and NF-kB pathways are commonly activated signaling pathways, but these pathways are downregulated by melittin, a main component of bee venom. In this study, a polymersome based on a poly (lactic acid) (PLA)-hyaluronic acid (HA) (20k-10k) di-block copolymer and encapsulating melittin and doxorubicin was developed to overcome anticancer resistance and enhance chemotherapeutic efficacy. Through the simultaneous delivery of doxorubicin and melittin, PI3K/Akt and NF-κB pathways could be effectively inhibited, thereby downregulating P-gp and successfully enhancing chemotherapeutic efficacy. In conclusion, a polymersome carrying an anticancer drug and melittin could overcome MDR by regulating P-gp overexpression pathways.
Keyphrases
- pi k akt
- signaling pathway
- cell proliferation
- cell cycle arrest
- hyaluronic acid
- multidrug resistant
- drug delivery
- induced apoptosis
- lactic acid
- epithelial mesenchymal transition
- oxidative stress
- cancer therapy
- squamous cell carcinoma
- emergency department
- escherichia coli
- pseudomonas aeruginosa
- cystic fibrosis
- endoplasmic reticulum stress
- toll like receptor
- candida albicans