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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Aptamer functionalized nucleic acid nano drug for targeted synergistic therapy for colon cancer
Liye Zhu1,2, Jieyu Yuhan1,3, Hao Yu1,3
1Food Laboratory of Zhongyuan, Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, No. 17 Qinghua Donglu, Beijing, 100083, China.
Abstract:
Due to its complicated pathophysiology, propensity for metastasis, and poor prognosis, colon cancer is challenging to treat and must be managed with a combination of therapy. Using rolling circle transcription (RCT), this work created a nanosponge therapeutic medication system (AS1411@antimiR-21@Dox). Using the AS1411 aptamer, this approach accomplished targeted delivery to cancer cells. Furthermore, analysis of cell viability, cell apoptosis, cell cycle arrest, reactive oxygen species (ROS) content, and mitochondrial membrane potential (MMP) levels revealed that functional nucleic acid nanosponge drug (FND) can kill cancer cells. Moreover, transcriptomics uncovered a putative mechanism for the FND anti-tumor effect. These pathways, which included mitotic metaphase and anaphase as well as the SMAC-mediated dissociation of the IAP: caspase complexes, were principally linked to the cell cycle and cell death. In conclusion, by triggering cell cycle arrest and apoptosis, the nano-synergistic therapeutic system allowed for the intelligent and effective targeted administration of RNA and chemotherapeutic medicines for colon cancer treatment. The system allowed for payload efficiency while being customizable, targeted, reliable, stable, and affordable.
Insights
This study developed a novel nanosponge drug delivery system for colon cancer, combining targeted RNA and chemotherapy to effectively kill cancer cells by inducing apoptosis and cell cycle arrest.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Colon cancer presents complex challenges due to its pathophysiology, metastasis, and poor prognosis, necessitating combination therapies.
- Current treatment strategies require improvement in targeted delivery and efficacy.
Purpose of the Study:
- To develop a functional nucleic acid nanosponge drug (FND) delivery system for targeted colon cancer therapy.
- To investigate the anti-tumor mechanisms of the FND system, including its effects on cell viability, apoptosis, cell cycle, ROS, and mitochondrial membrane potential.
Main Methods:
- Utilized rolling circle transcription (RCT) to fabricate the AS1411@antimiR-21@Dox nanosponge system.
- Employed the AS1411 aptamer for targeted delivery to colon cancer cells.
- Conducted comprehensive in vitro analyses including cell viability, apoptosis assays, cell cycle analysis, ROS quantification, and mitochondrial membrane potential measurements.
- Performed transcriptomic analysis to elucidate the anti-tumor mechanisms.
Main Results:
- The FND system demonstrated effective targeted delivery to cancer cells.
- Analysis confirmed the FND's ability to induce cancer cell death by reducing cell viability, increasing apoptosis, causing cell cycle arrest, altering ROS levels, and affecting mitochondrial membrane potential.
- Transcriptomic data revealed that the FND's anti-tumor effects are mediated through pathways involving cell cycle regulation (mitotic metaphase and anaphase) and apoptosis induction (SMAC-mediated dissociation of IAP: caspase complexes).
Conclusions:
- The developed nano-synergistic therapeutic system enables intelligent and effective targeted co-delivery of RNA and chemotherapeutic agents for colon cancer treatment.
- The FND system triggers cell cycle arrest and apoptosis, offering a customizable, targeted, reliable, stable, and affordable approach to colon cancer therapy with high payload efficiency.
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