3D-printing-assisted synthesis of paclitaxel-loaded niosomes functionalized by cross-linked gelatin/alginate
Fatemeh Hosseini1, Masoumeh Mirzaei Chegeni2, Ali Bidaki1
1Chemical Engineering Department, Faculty of Engineering, Ferdowsi University of Mashhad, Mashhad, Iran.
Abstract:
Breast cancer is one of the most lethal cancers, especially in women. Despite many efforts, side effects of anti-cancer drugs and metastasis are still the main challenges in breast cancer treatment. Recently, advanced technologies such as 3D-printing and nanotechnology have created new horizons in cancer treatment. In this work, we report an advanced drug delivery system based on 3D-printed gelatin-alginate scaffolds containing paclitaxel-loaded niosomes (Nio-PTX@GT-AL). The morphology, drug release, degradation, cellular uptake, flow cytometry, cell cytotoxicity, migration, gene expression, and caspase activity of scaffolds, and control samples (Nio-PTX, and Free-PTX) were investigated. Results demonstrated that synthesized niosomes had spherical-like, in the range of 60-80 nm with desirable cellular uptake. Nio-PTX@GT-AL and Nio-PTX had a sustained drug release and were biodegradable. Cytotoxicity studies revealed that the designed Nio-PTX@GT-AL scaffold had <5 % cytotoxicity against non-tumorigenic breast cell line (MCF-10A) but showed 80 % cytotoxicity against breast cancer cells (MCF-7), which was considerably more than the anti-cancer effects of control samples. In migration evaluation (scratch-assay), approximately 70 % reduction of covered surface area was observed. The anticancer effect of the designed nanocarrier could be attributed to gene expression regulation, where a significant increase in the expression and activity of genes promoting apoptosis (CASP-3, CASP-8, and CASP-9) and inhibiting metastasis (Bax, and p53) and a remarkable decrease in metastasis-enhancing genes (Bcl2, MMP-2, and MMP-9) were observed. Also, flow cytometry results declared that Nio-PTX@GT-AL reduced necrosis and increased apoptosis considerably. The results of this study prove that employing 3D-printing and niosomal formulation is an effective approach in designing nanocarriers for efficient drug delivery applications.
Insights
This study introduces a 3D-printed scaffold with paclitaxel-loaded niosomes for advanced breast cancer treatment. The novel drug delivery system effectively targets cancer cells, reduces metastasis, and enhances apoptosis with minimal toxicity.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapy
Background:
- Breast cancer remains a leading cause of death, with drug side effects and metastasis posing significant challenges.
- Advanced technologies like 3D-printing and nanotechnology offer promising new avenues for cancer treatment.
Purpose of the Study:
- To develop and evaluate an advanced drug delivery system for breast cancer treatment using 3D-printed scaffolds.
- To investigate the efficacy of paclitaxel-loaded niosomes within gelatin-alginate scaffolds (Nio-PTX@GT-AL).
Main Methods:
- Synthesis and characterization of niosomes and 3D-printed scaffolds.
- Evaluation of drug release kinetics, biodegradability, cellular uptake, and cytotoxicity.
- Assessment of anti-metastatic effects, gene expression, and apoptosis via flow cytometry and caspase activity assays.
Main Results:
- Niosomes (60-80 nm) exhibited desirable cellular uptake. The Nio-PTX@GT-AL scaffold demonstrated sustained drug release and biodegradability.
- The Nio-PTX@GT-AL scaffold showed high cytotoxicity (80%) against breast cancer cells (MCF-7) with low toxicity (<5%) against non-tumorigenic cells (MCF-10A).
- Significant reduction in cell migration (70%), increased apoptosis, and modulation of key genes involved in apoptosis and metastasis were observed.
Conclusions:
- 3D-printed gelatin-alginate scaffolds loaded with paclitaxel-niosomes represent an effective nanocarrier system for breast cancer therapy.
- This approach shows potential for enhancing drug delivery efficiency, reducing side effects, and combating metastasis.
