Folate-targeted liposome encapsulating chitosan/oligonucleotide polyplexes for tumor targeting

Area of Science:

• Biotechnology
• Nanomedicine
• Drug Delivery Systems

Background:

• Liposomes encapsulating polyethylenimine/oligonucleotides were effective for in vivo nucleic acid delivery.
• Polyethylenimine toxicity hinders clinical application of these nanocarriers.

Purpose of the Study:

• To develop a clinically applicable liposome encapsulating polyplexes by replacing polyethylenimine with chitosan.
• To create and characterize liposome encapsulating low-molecular weight chitosan (LMWC)/oligonucleotide (ODN) polyplexes [LS(CO)] and folate-targeted versions [FLS(CO)].

Main Methods:

• Formulation of LMWC/ODN polyplexes at pH 5.5 and N/P ratio 10.
• Encapsulation of polyplexes into anionic liposomes via membrane extrusion.
• Preparation of folate-targeted liposomes by incorporating folate-conjugated phospholipid.
• Characterization of size, zeta potential, colloidal stability, cellular uptake, and cytotoxicity.

Main Results:

• LS(CO) and FLS(CO) exhibited narrow size distribution (~130 nm), neutral zeta potentials, and stability for 7 days.
• FLS(CO) demonstrated enhanced cellular uptake in B16F10 melanoma cells compared to LS(CO).
• LS(CO) displayed significantly reduced toxicity versus polyethylenimine-based liposomes.

Conclusions:

• Liposomes encapsulating LMWC/ODN polyplexes are a promising, biocompatible nanocarrier for oligonucleotide therapeutics.
• Chitosan-based lipoplexes offer a safer alternative for clinical translation in nucleic acid therapy.
• Folate targeting enhances cellular uptake, potentially improving therapeutic efficacy.