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Preparation and Characterization of SDF-1α-Chitosan-Dextran Sulfate Nanoparticles
Published on: January 22, 2015
SiRNA/DOX lodeded chitosan based nanoparticles: Development, Characterization and in vitro evaluation on A549 lung
M Seifi-Najmi1, M Hajivalili2, R Safaralizadeh3
1Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences Tabriz Iran.
Abstract:
High-mobility group AT-hook2 (HMGA2), involved in epithelial mesenchymal transition (EMT) process, has a pivotal role in lung cancer metastasis. Lung cancer therapy with HMGA2 suppressing small interfering RNA (siRNA) has been introduced recently while doxorubicin (DOX) has been used as a frequent cancer chemotherapy agent. Both reagents have been faced with obstacles in clinic which make them ineffective. NanoParticles (NPs) provided a platform for efficient co delivery of the anticancer drugs. The aim of this study was production and in vitro characterization of different pharmacological groups (siRNA, DOX or siRNA-DOX) of carboxymethyl dextran thrimethyl chitosan nanoparticles (CMDTMChiNPs) on cytotoxicity, gene expression, apoptosis and migration of metastatic lung cancer cell line (A-549). CMDTMChiNPs were synthesized and encapsulated with siRNA, DOX or siRNA-DOX. Then the effects of HMGA2 siRNA and DOX co delivery was assessed in A549 viability and target genes (HMGA2, Ecadherin, vimentin and MMP9) by MTT and real time PCR, respectively. In addition capability of apoptosis induction and anti-migratory features of formulated NPs were analyzed by flowcytometry and wound healing assays. SiRNA-DOX-CMDTM ChiNPs approximate size were 207±5 with poly dispersity index (PDI) and zeta potential of 0.4 and 16.3±0.3, respectively. NPs loaded with DOX and siRNA were the most efficient drug formulations in A549 cell cytotoxicity, altering of EMT markers, apoptosis induction and migration inhibition. Generally our results showed that co delivery of HMGA2 siRNA and DOX by novel designed CMDTMChiNPs is a new therapeutic approach with great potential efficiency for lung cancer treatment.
Insights
This study developed novel nanoparticles for co-delivery of HMGA2 siRNA and doxorubicin to combat lung cancer metastasis. The combined therapy effectively reduced cancer cell viability, inhibited migration, and induced apoptosis, showing promise for improved lung cancer treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- High-mobility group AT-hook2 (HMGA2) promotes lung cancer metastasis via epithelial-mesenchymal transition (EMT).
- Current therapies like HMGA2 siRNA and doxorubicin (DOX) face clinical limitations.
- Nanoparticles offer a platform for co-delivery of therapeutic agents.
Purpose of the Study:
- To synthesize and characterize carboxymethyl dextran thrimethyl chitosan nanoparticles (CMDTMChiNPs) for co-delivery of HMGA2 siRNA and DOX.
- To evaluate the in vitro efficacy of these nanoparticles on lung cancer cells (A-549).
Main Methods:
- Carboxymethyl dextran thrimethyl chitosan nanoparticles (CMDTMChiNPs) were synthesized and loaded with siRNA, DOX, or both (siRNA-DOX).
- Cytotoxicity, gene expression (HMGA2, Ecadherin, vimentin, MMP9), apoptosis, and migration were assessed using MTT assays, real-time PCR, flow cytometry, and wound healing assays.
Main Results:
- SiRNA-DOX-CMDTMChiNPs exhibited an approximate size of 207±5 nm with a PDI of 0.4 and zeta potential of 16.3±0.3.
- Co-delivery of siRNA and DOX via CMDTMChiNPs demonstrated superior efficacy in reducing A549 cell cytotoxicity.
- The combined therapy significantly altered EMT markers, induced apoptosis, and inhibited cancer cell migration.
Conclusions:
- Co-delivery of HMGA2 siRNA and DOX using novel CMDTMChiNPs represents a promising therapeutic strategy for lung cancer.
- This approach addresses limitations of individual therapies and offers enhanced anti-cancer effects.
