Efficient intracellular delivery of functional proteins using cationic polymer core/shell nanoparticles

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapy

Background:

• Effective intracellular delivery of therapeutic proteins like anticancer lectin A-chain is crucial for cancer treatment.
• Conventional delivery methods often face challenges with protein stability, cellular uptake, and targeted delivery.
• Biodegradable cationic nanoparticles offer a potential solution for enhanced protein delivery.

Purpose of the Study:

• To fabricate and characterize novel cationic core/shell nanoparticles for delivering lectin A-chain.
• To evaluate the efficiency of these nanoparticles in binding and delivering lectin A-chain.
• To compare the cellular uptake and cytotoxicity of lectin A-chain delivered by nanoparticles versus a commercial agent (BioPorter).

Main Methods:

• Self-assembly of biodegradable, cationic, and amphiphilic copolymer poly{N-methyldietheneamine sebacate)-co-[(cholesteryl oxocarbonylamido ethyl) methyl bis(ethylene) ammonium bromide] sebacate}, P(MDS-co-CES), into core/shell nanoparticles.
• Binding of lectin A-chain onto the nanoparticle surfaces at various mass ratios.
• Characterization of nanoparticle/lectin A-chain complex size and zeta potential.
• Assessment of cellular uptake and cytotoxicity assays on multiple cancer cell lines (MDA-MB-231, HeLa, HepG2, 4T1).

Main Results:

• Efficient binding of lectin A-chain onto P(MDS-co-CES) nanoparticles was achieved at high nanoparticle-to-lectin mass ratios.
• Nanoparticle/lectin A-chain complexes exhibited optimal size (~150 nm) and zeta potential (~+30 mV) at mass ratio ≥ 50, outperforming BioPorter/lectin A-chain complexes in size and zeta potential.
• Significantly enhanced cellular uptake of lectin A-chain was observed with the nanoparticle delivery system compared to BioPorter.
• Lecthin A-chain delivered by nanoparticles demonstrated markedly higher cytotoxicity against tested cancer cell lines, with significantly lower IC50 values than when delivered by BioPorter.

Conclusions:

• Biodegradable cationic P(MDS-co-CES) nanoparticles are effective carriers for intracellular delivery of lectin A-chain.
• The nanoparticle-based delivery system enhances protein cellular uptake and anticancer efficacy.
• These nano-sized particles represent a promising strategy for improving the therapeutic potential of biologically active proteins in cancer treatment.