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Dual Bioluminescence Imaging of Tumor Progression and Angiogenesis
Published on: August 1, 2019
A double safety lock tumor-specific device for suicide gene therapy in breast cancer
Maria J Piña1, Alessandra Girotti1, Sofía Serrano1
1BIOFORGE (Group for Advanced Materials and Nanobiotechnology), CIBER-BBN, University of Valladolid, Valladolid, Spain.
Abstract:
The complexity and continuous evolution of cancer make the design of novel strategies of treatment a constant challenge in biomedicine. Moreover, most of cancer treatments are still not tumor-specific and provoke high systemic toxicity. Herein we have developed a novel selective nanodevice to eliminate tumor cells while leaving healthy ones intact. To achieve this objective, a polyplex carrier, comprising an elastin like-recombinamer covalently conjugated to an aptamer and complexed with therapeutic DNA, was tested. This carrier forms a double-lock multifunctional device due to specific binding to a tumor cell marker and the selective expression of therapeutic DNA inside human breast-cancer cells. Due to the stability provided by ELRs, the homogeneous population of polyplexes obtained showed selective toxicity against cancer cells in in vitro and in vivo assay. Inhibition of tumor progression was detected early being very significant at the end point, with a dose-dependent reduction in tumor mass. Histological studies revealed a specific reduction in tumor parenchyma and in specific tumor cell markers. These results represent an important step toward the rational development of an efficient, safe and more specialized gene-delivery device for tumor therapy.
Insights
Researchers developed a novel nanodevice using elastin-like recombinamers (ELRs) and aptamers for targeted cancer gene therapy. This selective system eliminates tumor cells with minimal toxicity, showing significant tumor reduction in vivo.
Area of Science:
- Biomedicine
- Nanotechnology
- Oncology
Background:
- Cancer treatment faces challenges due to tumor evolution and lack of specificity, leading to systemic toxicity.
- Current therapies often lack tumor specificity, harming healthy cells and causing side effects.
Purpose of the Study:
- To develop a novel, selective nanodevice for targeted elimination of tumor cells.
- To create a multifunctional gene-delivery system that minimizes toxicity to healthy cells.
Main Methods:
- A polyplex carrier was engineered using elastin-like recombinamers (ELRs) covalently conjugated to aptamers, complexed with therapeutic DNA.
- The nanodevice was designed for dual targeting: specific binding to tumor cell markers and selective DNA expression within cancer cells.
- In vitro and in vivo assays were conducted to evaluate the nanodevice's efficacy and toxicity.
Main Results:
- The ELR-based polyplexes demonstrated homogeneous populations and selective toxicity against cancer cells.
- Significant inhibition of tumor progression and dose-dependent reduction in tumor mass were observed.
- Histological studies confirmed specific reduction in tumor parenchyma and markers, indicating targeted action.
Conclusions:
- The developed nanodevice represents a significant advancement in targeted tumor therapy.
- This specialized gene-delivery system offers a potentially efficient and safer approach for cancer treatment.
- Further development of this multifunctional device holds promise for rational cancer therapy design.
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