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Heparin Biofunctionalized Selenium Nanoparticles as Potential Antiangiogenic-Chemotherapeutic Agents for Targeted
Mahaveer P Purohit1,2, Aditya K Kar1,2, Manisha Kumari3,2
1Water Analysis Laboratory, System Toxicology, and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh 226001, India.
Abstract:
Combining antiangiogenic and chemotherapeutic agents has shown promising clinical benefits in cancer cures when the therapeutic intervention takes into account the tissue and molecular targets. Moreover, the risk of induced drug resistance is minimized when multiple pathways are involved in the treatment regimen, yielding a better therapeutic outcome. Nanodrug delivery systems have proven to be a prudent approach to treating complex disease pathologies. As such, combining antiangiogenic and chemotherapeutic drugs within multimodal nanocarriers synergistically augments the clinical efficiency of the drugs. This study reports the combinatorial efficacy of heparin (Hep), selenium NPs (SeNPs), and doxorubicin (Dox) to inhibit tumor growth and progression. Both Se@Hep-NPs and Se@Hep-Dox-NPs with excellent water dispersity having a size and charge in the range of 250 ± 5 and 253 ± 5 nm and -53 ± 0.4 and -48.4 ± 6.4 mV, respectively, showed strong anticancer potential assessed through in vitro assays like cell viability, specificity, colony formation, and wound scratch in MCF7 cells. Strong synergistic interactions among SeNPs, Hep, and Dox in Se@Hep-Dox-NPs render it to be an antiangiogenic and proapoptotic cancer cell death inducers. In vivo imaging highlights the dual-mode attributes of Se@Hep-NPs with desirable passive tumor targeting and biomedical imaging ability when tagged with Cy7.5, while Se@Hep-Dox-NPs significantly reduce the tumor burden and prolong the longevity of subcutaneous EAC-bearing mice. Histopathology studies reveal no signs of toxicity in major organs. Collectively, these results qualify Se@Hep-Dox-NPs as a plausible clinical therapeutic candidate.
Insights
This study developed novel nanocarriers combining selenium nanoparticles (SeNPs), heparin (Hep), and doxorubicin (Dox) for enhanced cancer therapy. The Se@Hep-Dox-NPs demonstrated potent anti-tumor effects and safety in preclinical models.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Combining antiangiogenic and chemotherapeutic agents offers synergistic benefits in cancer treatment.
- Nanodrug delivery systems are effective for complex diseases, improving drug efficacy.
- Multimodal nanocarriers can enhance the clinical efficiency of combined therapies.
Purpose of the Study:
- To investigate the combinatorial efficacy of heparin (Hep), selenium NPs (SeNPs), and doxorubicin (Dox) for inhibiting tumor growth.
- To evaluate the anticancer potential of Se@Hep-NPs and Se@Hep-Dox-NPs in vitro and in vivo.
- To assess the safety and therapeutic viability of these nanocarriers as clinical candidates.
Main Methods:
- Synthesis and characterization of Se@Hep-NPs and Se@Hep-Dox-NPs, including size, charge, and dispersity.
- In vitro evaluation of anticancer activity using cell viability, specificity, colony formation, and wound scratch assays in MCF7 cells.
- In vivo studies involving tumor burden reduction, longevity assessment in EAC-bearing mice, and histopathology for toxicity analysis.
Main Results:
- Se@Hep-NPs and Se@Hep-Dox-NPs exhibited excellent water dispersity and anticancer potential in vitro.
- Se@Hep-Dox-NPs showed strong synergistic interactions, acting as antiangiogenic and proapoptotic agents.
- In vivo, Se@Hep-Dox-NPs significantly reduced tumor burden and prolonged survival with no observed organ toxicity.
Conclusions:
- Se@Hep-Dox-NPs demonstrate potent synergistic anti-tumor efficacy through antiangiogenic and proapoptotic mechanisms.
- The nanocarrier system offers dual-mode attributes for passive tumor targeting and imaging (Se@Hep-NPs).
- Se@Hep-Dox-NPs represent a promising and safe therapeutic candidate for clinical application in cancer treatment.

