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Updated: Dec 29, 2025
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Development of a nattokinase-polysialic acid complex for advanced tumor treatment
Yanmei Kou1, Rui Feng1, Jiepeng Chen2
1College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
Abstract:
Cancer-associated thrombus (CAT) impedes delivery of nanoparticles to tumor sites and also inhibits the ability of immune cells to detect and attack these tumors, particularly in advanced tumors with old thrombi. Nattokinase (NK) is an extract from a popular Japanese food, natto, which consists of boiled soybeans fermented with bacteria. Nattokinase exerts strong fibrinolytic and thrombolytic activities and can unblock blood vessels. To deliver NK to thrombus sites in tumors, we modified the surface of NK with polysialic acid (PSA), which formed complexes via electrostatic interactions, resulting in NK-PSA. Particle size and zeta potential of NK-PSA were evaluated, and differential scanning calorimetry, Fourier-transform infrared spectroscopy, and morphological analyses of NK-PSA were performed. To determine the efficacy of the NK-PSA complex on delivery of nanoparticulate drugs, sialic acid-modified doxorubicin liposomes (DOX-SAL) were used as a model drug. In vivo pharmacokinetic and tissue distribution analyses showed that the blood clearance rate of DOX-SAL was significantly enhanced by NK-PSA, and NK-PSA increased accumulation of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR) labeled SAL (DiR-SAL) in tumors. Analysis of anti-tumor efficacy showed that the combination of NK-PSA and DOX-SAL enhanced anti-tumor activity. These results suggested that NK-PSA combined with DOX-SAL may be an effective strategy to clear CAT and increase the ability of nanoparticles and immune cells to reach tumors.
Insights
Nattokinase-polysialic acid (NK-PSA) complexes can break down cancer-associated thrombi (CAT). This improves nanoparticle and immune cell delivery to tumors, enhancing anti-tumor efficacy when combined with chemotherapy drugs.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Cancer-associated thrombus (CAT) hinders nanoparticle and immune cell delivery to tumors.
- Nattokinase (NK) possesses fibrinolytic and thrombolytic properties to dissolve blood clots.
- Targeting thrombi is crucial for improving cancer treatment efficacy.
Purpose of the Study:
- To develop a novel NK-PSA complex for targeted thrombus dissolution.
- To evaluate the efficacy of NK-PSA in enhancing drug delivery and anti-tumor activity.
- To investigate NK-PSA as a strategy to overcome CAT barriers in cancer therapy.
Main Methods:
- Modification of nattokinase (NK) with polysialic acid (PSA) to form NK-PSA complexes.
- Characterization of NK-PSA using particle size, zeta potential, DSC, FTIR, and morphological analyses.
- In vivo pharmacokinetic, tissue distribution, and anti-tumor efficacy studies using doxorubicin liposomes (DOX-SAL).
Main Results:
- NK-PSA complexes were successfully synthesized and characterized.
- NK-PSA significantly enhanced the tumor accumulation of doxorubicin liposomes (DOX-SAL).
- The combination of NK-PSA and DOX-SAL demonstrated improved anti-tumor efficacy in vivo.
Conclusions:
- NK-PSA is a promising strategy for clearing cancer-associated thrombi.
- NK-PSA enhances nanoparticle drug delivery and anti-tumor immune responses.
- This approach holds potential for improving therapeutic outcomes in advanced cancers with thrombi.
