CN-121987825-A - Nano-selenium-Phellinus linteus polysaccharide composite carrier, preparation method and application thereof

CN121987825ACN 121987825 ACN121987825 ACN 121987825ACN-121987825-A

Abstract

The invention discloses a nano selenium-Phellinus linteus polysaccharide composite carrier, a preparation method and application thereof, wherein the composite carrier takes nano selenium particles as cores and Phellinus linteus polysaccharide as a coating layer, the Phellinus linteus polysaccharide is coated on the surface of nano selenium through electrostatic interaction and/or chemical bonding, is spherical particles with the wavelength of 20-100nm, has characteristic ultraviolet absorption peaks at 250nm, has the coating rate of not less than 80 percent, and is prepared by adopting a chemical reduction method and taking Phellinus linteus polysaccharide, sodium selenite and ascorbic acid as raw materials through liquid phase reduction and process optimization. The composite carrier induces iron overload and lipid peroxidation by excessively activating colorectal cancer cells ROS/Nrf2/HO-1, specifically induces iron death, can bypass a chemotherapy drug resistance mechanism, and has strong targeting and low toxicity. The preparation method is simple, convenient and controllable, the composite carrier has high stability and bioavailability and remarkable tumor inhibiting effect, can be prepared into various dosage forms, provides a novel efficient low-toxicity strategy for treating colorectal cancer, especially chemotherapy drug-resistant colorectal cancer, and has good clinical transformation prospect.

Inventors

SHI JIE
WANG XIN
ZHAO MENGXUE
LI CHAO
HUANG MENG
LIU HONG
WU QIAN
YUE JIANJUN
ZHANG YANCHEN

Assignees

无锡市惠山区人民医院

Dates

Publication Date: 20260508
Application Date: 20260313

Claims (10)

1. A nano selenium-Phellinus linteus polysaccharide composite carrier is characterized in that nano selenium particles are used as cores, phellinus linteus polysaccharide is used as a coating layer, the Phellinus linteus polysaccharide is combined on the surfaces of the nano selenium particles in a manner of electrostatic interaction and/or chemical bonding, and the composite carrier is nano spherical particles and can specifically induce colorectal cancer cells to generate iron death.
2. The nano selenium-Phellinus linteus polysaccharide composite carrier of claim 1, wherein the average particle size of the composite carrier is 20-100nm, the composite carrier has characteristic ultraviolet absorption peak at 250nm, and the composite carrier contains three elements of carbon, oxygen and selenium, and the encapsulation rate of Phellinus linteus polysaccharide in the composite carrier is more than or equal to 80%.
3. A method for preparing a nano selenium-Phellinus linteus polysaccharide composite carrier as set forth in claim 1 or 2, which is characterized by adopting a chemical reduction method, comprising the following specific steps: S1, preparing a Phellinus linteus polysaccharide solution, a sodium selenite solution and an ascorbic acid solution as reaction raw materials; S2, mixing the reaction raw materials to perform liquid phase reduction reaction, so that sodium selenite is reduced into nano-selenium particles, and meanwhile, phellinus linteus polysaccharide is coated on the surfaces of the nano-selenium particles to form a composite carrier; s3, screening and optimizing the technological parameters of the reaction product to obtain the nano selenium-Phellinus linteus polysaccharide composite carrier with uniform particle size and good stability.
4. The method for preparing the nano-selenium-Phellinus linteus polysaccharide composite carrier according to claim 3, wherein in the step S1, the volume ratio of Phellinus linteus polysaccharide solution, sodium selenite solution and ascorbic acid solution is 1:1:1; In the step S2, the reduction reaction is an aqueous phase reaction at normal temperature and normal pressure, and the reaction time is 2-6h.
5. The method for preparing the nano selenium-Phellinus linteus polysaccharide composite carrier according to claim 3, wherein in the step S3, the process parameter screening and optimization comprises the regulation and control of Phellinus linteus polysaccharide solution concentration, sodium selenite solution concentration, stirring rate and reaction pH value, wherein the regulation and control range is that the mass concentration of Phellinus linteus polysaccharide solution is 0.5-2mg/mL, the concentration of sodium selenite solution is 1-5mmol/L, the stirring rate is 200-600r/min, and the reaction pH value is 6-8; the prepared composite carrier is also subjected to physical and chemical characteristic characterization by one or more means of transmission electron microscopy, dynamic light scattering, fourier transform infrared spectrum and X-ray diffraction.
6. Use of a nano selenium-Phellinus linteus polysaccharide complex carrier according to claim 1 or 2 for preparing a medicament for treating colorectal cancer in a manner of inducing colorectal cancer cell iron death.
7. The use of a nano selenium-Phellinus linteus polysaccharide composite carrier according to claim 6 for preparing a medicament, wherein the medicament induces iron death of colorectal cancer cells by overactivating intracellular ROS/Nrf2/HO-1 signaling pathway, thereby inducing intracellular iron overload and lipid peroxidation storm.
8. The application of the nano-selenium-Phellinus linteus polysaccharide composite carrier in preparing medicines, as claimed in claim 6, is characterized in that the administration mode of the anti-colorectal cancer medicines is gastric lavage administration, and the medicine dosage forms are one or more of injection, suspension and capsule.
9. The application of the nano-selenium-Phellinus linteus polysaccharide composite carrier in preparing medicines, as claimed in claim 6, is characterized in that the nano-selenium-Phellinus linteus polysaccharide composite carrier is used as the only active ingredient in the medicines for resisting colorectal cancer or is used in a synergistic compatibility with other active ingredients for resisting colorectal cancer.
10. The use of a nano selenium-Phellinus linteus polysaccharide composite carrier according to any one of claims 6-9 for preparing a medicament, wherein the anti-colorectal cancer medicament is suitable for the treatment of chemotherapy-resistant colorectal cancer, and can bypass the apoptotic escape of colorectal cancer cells and the chemotherapy-resistant mechanism to exert an anti-tumor effect.

Description

Nano-selenium-Phellinus linteus polysaccharide composite carrier, preparation method and application thereof Technical Field The invention relates to the technical field of biological medicine, in particular to a nano selenium-Phellinus linteus polysaccharide composite carrier, a preparation method and application thereof. Background Colorectal cancer is a malignant tumor with high digestive tract, the global incidence rate is in an increasing trend year by year, the incidence rate of the colorectal cancer is the third place of the malignant tumor, new incidence and death cases of colorectal cancer in China are also in a higher level, and the colorectal cancer is a malignant tumor with high incidence in partial areas, and a heavy burden is brought to a medical and health system. At present, the treatment of colorectal cancer is mainly based on a comprehensive scheme of surgery combined with radiotherapy and chemotherapy, but the problems of chemotherapy resistance, low immune treatment response rate, tumor recurrence and metastasis, serious systemic toxic and side effects of the drug and the like become main reasons for causing treatment failure, and the development of novel high-efficiency low-toxicity anti-colorectal cancer treatment strategies becomes urgent need of clinical research. Iron death is used as a programmed cell death mode driven by iron dependence and lipid peroxidation, has obvious mechanism differences with the traditional cell death modes such as apoptosis, necrosis and the like, colorectal tumor cells have inherent sensitivity to iron death due to active metabolism and enhanced iron uptake, and the iron death can bypass the apoptosis escape and chemotherapy drug resistance mechanisms of tumor cells, thereby providing a new strategy direction for overcoming colorectal cancer treatment resistance. However, the existing iron death inducer has the defects of low bioavailability, poor targeting property and large systemic toxicity, and is difficult to realize clinical transformation, so that how to realize efficient targeting delivery of the iron death inducer and accurately regulate and control an iron death related signal pathway becomes a key problem to be solved in the field of cancer treatment. The ROS/Nrf2/HO-1 pathway is a core pathway for regulating iron death, has dynamic property and background dependence, is suitable for activation to help cell survival, and can promote iron death to occur when overactivation is carried out, so that the targeted regulation of the balance of the pathway becomes an effective treatment thought for inducing iron death of tumor cells. Selenium is used as an essential trace element with antitumor potential, can inhibit colorectal cancer cell proliferation by regulating oxidation stress, inducing cell cycle retardation and other ways, but has a narrow treatment window of effective dose and toxic dose, and limits clinical application, and nano selenium particles have higher bioavailability, bioactivity and lower toxicity compared with inorganic selenium and organic selenium, have tumor selectivity, but have the problems of easy agglomeration, easy bioavailability and easy loss of activity in a liquid phase, and a proper stabilizer is needed to improve the stability. The natural active polysaccharide becomes an ideal template for stabilizing the nano-selenium particles because of the enrichment of hydrophilic groups, and the Phellinus linteus polysaccharide has good biocompatibility and immunoregulation function as the natural active polysaccharide, can obviously enhance the generation of ROS in cells and stabilize HO-1 expression, is one of a few natural polysaccharides which can trigger ROS storm and regulate HO-1 at the same time, and can form a synergistic anti-tumor system by combining with nano-selenium. Based on the method, a nano-selenium composite carrier wrapped by Phellinus linteus polysaccharide is constructed, so that the ROS/Nrf2/HO-1 axis can be efficiently regulated and controlled, colorectal cancer cell iron death can be accurately induced, and the method becomes an important research direction for solving the existing dilemma of colorectal cancer treatment and optimizing an iron death induction strategy. Disclosure of Invention This section is intended to outline some aspects of embodiments of the application and to briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section as well as in the description of the application and in the title of the application, which may not be used to limit the scope of the application. Therefore, the invention aims to provide a nano selenium-Phellinus linteus polysaccharide composite carrier, a preparation method and application thereof, so as to solve the problems in the prior art. In order to solve the technical problems, according to one aspect of the present invention, the following technical solutions are provided: A nano-selenium-Phellinus linteus polys