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Polyethylenimine-Conjugated Hydroxyethyl Cellulose for Doxorubicin/Bcl-2 siRNA Co-Delivery Systems
Jiwon Park1, Seoyoung Kim1, Tae-Il Kim1,2,3
1Department of Agriculture, Forestry and Bioresources, College of Agriculture and Life Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
Pharmaceutics
|February 25, 2023
Summary
Hydroxyethyl cellulose conjugated with polyethylenimine (HECP2k) effectively co-delivers doxorubicin and Bcl-2 siRNA. This novel system enhances anti-cancer effects by inducing apoptosis, showing great potential for cancer therapy.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapy
Background:
- Hydroxyethyl cellulose (HEC) is a biocompatible, water-soluble polysaccharide with pharmaceutical potential.
- Polyethylenimine (PEI) is a common non-viral vector for gene delivery, but often exhibits toxicity.
- Developing safe and effective co-delivery systems for chemotherapy drugs and gene silencing agents is crucial for cancer treatment.
Purpose of the Study:
- To synthesize and characterize polyethylenimine2k (PEI2k)-conjugated hydroxyethyl cellulose (HECP2k) for co-delivery of doxorubicin (Dox) and Bcl-2 siRNA.
- To evaluate the physicochemical properties, cellular uptake, transfection efficiency, and anti-cancer efficacy of the HECP2k-based delivery system.
- To assess the potential of HECP2k as a synergistic co-delivery carrier for enhanced cancer therapy.
Main Methods:
- HECP2k synthesis via reductive amination of PEI2k with periodate-oxidized HEC.
- Characterization using 1H NMR, 13C NMR, primary amine quantification, FT-IR, and GPC.
- Complexation with pDNA, pDNA gel electrophoresis, Zeta-sizer analysis, cytotoxicity assays, flow cytometry, confocal microscopy, and in vitro anti-cancer efficacy studies.
Main Results:
- HECP2ks successfully condensed pDNA into nano-sized complexes (100-300 nm, ~30 mV).
- HECP2k exhibited low cytotoxicity and superior transfection efficiency and serum stability compared to PEI25k.
- HECP2k 10X demonstrated enhanced cellular uptake, efficient endosome escape, and synergistic anti-cancer effects when co-delivering Dox and Bcl-2 siRNA, inducing apoptosis.
Conclusions:
- HECP2k is a safe and effective non-viral vector for co-delivery of doxorubicin and Bcl-2 siRNA.
- The HECP2k-based system shows significant potential for synergistic cancer therapy through enhanced apoptosis induction.
- HECP2k represents a promising biomaterial for developing advanced drug and gene delivery systems in oncology.
Keywords:
Bcl-2 siRNAanti-cancer effectdoxorubicindrug resistancegene/drug delivery systemshydroxyethyl cellulosepolyethylenimineserum stability
