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Updated: Jul 31, 2025
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Precision Therapy of Recurrent Breast Cancer through Targeting Different Malignant Tumor Cells with a
Juan Chen1,2, Jinjin Li1, Xiaolu Sun1
1Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.
Abstract:
Heterogeneity and drug resistance of tumor cells are the leading causes of incurability and poor survival for patients with recurrent breast cancer. In order to accurately deliver the biological anticancer drugs to different subtypes of malignant tumor cells for omnidirectional targeted treatment of recurrent breast cancer, a distinct design is demonstrated by embedding liposome-based nanocomplexes containing pro-apoptotic peptide and survivin siRNA drugs (LPR) into Herceptin/hyaluronic acid cross-linked nanohydrogels (Herceptin-HA) to fabricate a HER2/CD44-targeted hydrogel nanobot (named as ALPR). ALPR delivered cargoes to the cells overexpressing CD44 and HER2, followed by Herceptin-HA biodegradation, subsequently, the exposed lipid component containing DOPE fused with the endosomal membrane and released peptide and siRNA into the cytoplasm. These experiments indicated that ALPR can specifically deliver Herceptin, peptide, and siRNA drugs to HER2-positive SKBR-3, triple-negative MDA-MB-231, and HER2-negative drug-resistant MCF-7 human breast cancer cells. ALPR completely inhibited the growth of heterogeneous breast tumors via multichannel synergistic effects: disrupting mitochondria, downregulating the survivin gene, and blocking HER2 receptors on the surface of HER2-positive cells. The present design overcomes the chemical drug resistance and opens a feasible route for the combinative treatment of recurrent breast cancer, even other solid tumors, utilizing different kinds of biological drugs.
Insights
A novel hydrogel nanobot (ALPR) effectively targets and treats heterogeneous breast cancer by delivering multiple drugs. This approach overcomes drug resistance and offers a new strategy for recurrent breast cancer treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Tumor heterogeneity and drug resistance are major challenges in treating recurrent breast cancer, leading to poor patient outcomes.
- Effective delivery of multiple therapeutic agents to diverse cancer cell subtypes is crucial for overcoming treatment resistance.
Purpose of the Study:
- To design and fabricate a novel hydrogel nanobot (ALPR) for targeted delivery of biological anticancer drugs to heterogeneous breast cancer cells.
- To evaluate the efficacy of ALPR in overcoming drug resistance and achieving synergistic therapeutic effects in recurrent breast cancer models.
Main Methods:
- Fabrication of ALPR by embedding liposome-based nanocomplexes (LPR) containing pro-apoptotic peptide and survivin siRNA into Herceptin/hyaluronic acid cross-linked nanohydrogels (Herceptin-HA).
- Assessment of ALPR's targeting capability to HER2 and CD44 overexpressing cells.
- Evaluation of ALPR's drug release mechanism and cellular uptake.
- In vitro and in vivo studies to assess the anti-cancer effects of ALPR on various human breast cancer cell lines and tumor growth.
Main Results:
- ALPR demonstrated specific delivery of Herceptin, peptide, and siRNA to HER2-positive, triple-negative, and HER2-negative drug-resistant breast cancer cells.
- ALPR induced synergistic anti-cancer effects by disrupting mitochondria, downregulating survivin gene expression, and blocking HER2 receptors.
- Complete inhibition of heterogeneous breast tumor growth was observed, indicating ALPR's high therapeutic efficacy.
Conclusions:
- The developed ALPR nanobot overcomes chemical drug resistance in recurrent breast cancer.
- This innovative design provides a feasible platform for combinational therapy of recurrent breast cancer and potentially other solid tumors using diverse biological drugs.
