Related Experiment Video
Updated: May 22, 2025
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Framework nucleic acid-programmed aptamer-paclitaxel conjugates as targeted therapeutics for triple-negative breast
Lin Li1, Pengyao Wei1, Tong Kong1
1Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology, Ningbo Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering of Chinese Academy of Sciences, Ningbo, 315300, P. R. China. wangkaizhe@nimte.ac.cn.
Abstract:
Triple-negative breast cancer (TNBC) is highly invasive with a poor prognosis, and chemotherapy remains the clinical treatment of choice. Paclitaxel is a commonly used first-line chemotherapy drug, but its untargeted distribution poses clinical challenges. Inspired by antibody-drug conjugates, we develop a precisely structured framework nucleic acid-programmed aptamer-paclitaxel conjugate (FAPC) with chemically well-defined paclitaxel loading dosing, enabling the regulation of receptor-aptamer affinity to facilitate tumor-targeted chemotherapy. Utilizing framework nucleic acids as a precise addressing scaffold, we organize the AS1411 aptamer with accurate intermolecular spacing and find that an inter-aptamer spacing of 19.04 nm could enhance the affinity of the FAPC for tumor cells. Then, the multifunctional FAPC can disrupt actin reorganization to achieve cytotoxicity in tumor cells. Furthermore, the AS1411-specifically modified FAPC further enhances the structure-dependent selective accumulation of drugs at tumor sites in a human xenograft model of triple-negative breast cancer, subsequently leading to significantly improved antitumor efficacy and reduced toxicity. The FAPC provides a precisely programmable platform for efficient targeted delivery of chemotherapeutic agents to malignancies.
Insights
Researchers developed a novel aptamer-paclitaxel conjugate (FAPC) for targeted triple-negative breast cancer (TNBC) chemotherapy. This framework nucleic acid platform precisely delivers paclitaxel, enhancing efficacy and reducing toxicity in preclinical models.
Area of Science:
- Biochemistry
- Nanotechnology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its invasiveness and poor prognosis.
- Current chemotherapy, like paclitaxel, suffers from non-specific distribution, limiting efficacy and increasing side effects.
- Developing targeted drug delivery systems is crucial for improving TNBC treatment outcomes.
Purpose of the Study:
- To engineer a precisely structured framework nucleic acid-programmed aptamer-paclitaxel conjugate (FAPC) for targeted chemotherapy.
- To optimize the FAPC by regulating aptamer spacing for enhanced tumor cell affinity.
- To evaluate the antitumor efficacy and safety of FAPC in preclinical models of TNBC.
Main Methods:
- Fabrication of a framework nucleic acid scaffold to precisely position the AS1411 aptamer.
- Optimization of inter-aptamer spacing (19.04 nm) to maximize FAPC affinity for tumor cells.
- In vitro assessment of FAPC-induced cytotoxicity via disruption of actin reorganization.
- In vivo evaluation of FAPC's tumor-targeting, efficacy, and toxicity in a human TNBC xenograft model.
Main Results:
- The optimized FAPC demonstrated enhanced affinity for tumor cells, attributed to specific inter-aptamer spacing.
- FAPC effectively induced cytotoxicity in tumor cells by disrupting actin reorganization.
- AS1411-modified FAPC exhibited structure-dependent selective drug accumulation at tumor sites.
- Significant improvements in antitumor efficacy and reduced systemic toxicity were observed in vivo.
Conclusions:
- Framework nucleic acid-programmed aptamer-paclitaxel conjugates (FAPC) offer a precisely programmable platform for targeted chemotherapy.
- Optimized FAPC demonstrates potential for efficient and safer treatment of triple-negative breast cancer.
- This approach advances the development of nanomedicines for targeted cancer therapy.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:15Drugs that Stabilize Microtubules