Development of Polymersomes Co-Delivering Doxorubicin and Melittin to Overcome Multidrug Resistance

Abstract

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.

Hyaluronan‐Sphingosine Polymersomes for Treatment of Ocular Neovascularization: Synthesis and Evaluation

“…The HA‐Sph amphiphiles were self‐assembled into polymersomes by utilizing the solvent evaporation method. [ 25 ] Size, surface charge, and morphology of HA‐Sph polymersomes were investigated by dynamic light scattering (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) techniques (Table 1 and Figure 3 ). All the PDI (polydispersity index) values of HA‐Sph polymersomes are around 0.2 which indicates a homogenous distribution of particle sizes for all three samples.…”

“…HA‐Sph amphiphilic polymers were self‐assembled into polymersomes via solvent evaporation method (Figure 1C). [ 25b ] Amphiphilic polymers were completely dispersed in diethyl ether. The polymers in diethyl ether were vortexed and sonicated for 30 min in a sonic bath.…”

Polymersomes as the Next Attractive Generation of Drug Delivery Systems: Definition, Synthesis and Applications

“…In another recent example of combination therapy, PLA-HA polymersome delivered Dox with peptide melittin. In multidrug-resistant MCF-7 cells, melittin suppressed efflux pumps and showed synergistic cytotoxic effects in combination with Dox [120].…”

Recent advances in melittin-based nanoparticles for antitumor treatment: from mechanisms to targeted delivery strategies

“…In addition to a direct tumor cell killing effect, MLT also possesses multiple biological functions, including gene expression regulation and immunomodulatory effects [4,5]. Thus, MLT is a potential anticancer candidate due to its remarkable antitumor activity and immunomodulatory effects as well as its ability to overcome tumor drug resistance [6][7][8].…”