Preparation method of tumor-targeted acid-sensitivity prodrug-magnetic nanoparticle conjugate and application thereof

Abstract

The invention discloses a preparation method of a tumor-targeted acid-sensitivity prodrug-magnetic nanoparticle conjugate and an application thereof. The method comprises the following steps: preparing a tumor-targeted acid-sensitivity prodrug from raw materials such as hyaluronic acid and adriacin doxorubicin; preparing an amino-containing magnetic nanoparticle through a coprecipitation method and modification of an amino silane coupling agent; and finally carrying out chemical couplong on the hyaluronic acid tumor-targeted acid-sensitivity prodrug and the magnetic nanoparticle through amidation reaction. The tumor-targeted acid-sensitivity prodrug-magnetic nanoparticle conjugate prepared by the method has good water dispersion stability; the superparamagnetism of the magnetic nanoparticle is not affected; long cycle of the magnetic nanoparticle in vivo is facilitated; moreover, the nanoparticle is also coupled to an anti-tumor medicine adriacin doxorubicin, so as to be effectively released in weak-acidity parts such as tumor cells; and the preparation method is expected to be applied to the fields such as diagnosis and treatment of tumors.

Description

technical field [0001] The invention belongs to the technical field of biomedical materials, and in particular relates to a preparation method and application of a tumor-targeting acid-sensitive prodrug and magnetic nanoparticle conjugate. Background technique [0002] In traditional clinical applications, tumor diagnosis and treatment are relatively independent processes, and patients often need to undergo a process of first diagnosis and then treatment. The interval is long, which often delays the best time for disease treatment; Drugs often have certain side effects, and administration in two doses will increase unnecessary pain and risk for patients. Therefore, it is of great significance to design and prepare multifunctional molecular imaging probes integrating diagnosis and treatment. So far, the research on this kind of materials has mostly focused on liposomes or amphiphilic polymer micelles that can simultaneously load superparamagnetic iron oxide nanoparticles (Su...

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Problems solved by technology

However, in order to prepare amphiphilic polymers for the formation of micelles, it is not only necessary to simultaneously introduce hydrophilic and hydrophobic macromolecular segments with the help of complex chemical reactions and suitable solvents, but also to adjust the reaction formula system and A series of amphiphilic polymer samples were synthesized and characterized by means of a variety of analytical testing methods to optimize the structure and composition of the desired amphiphilic polymer and ensure the formation of related micelles; The process is usually very complicated and is easily affected by the structure, composition and concentration of the polymer itself, as well as the composition of the solvent system, temperature and pH, and is difficult to control; moreover, the yield of amphiphilic polymer micelles is usually low, and at the same time The ability of SPIO and anti-tumor drugs is limited, and in some cases, it is difficult to achieve the effective concentration of SPIO and anti-tumor drugs for clinical use; in addition, in order to enhance the specific recognition of such carrier materials for tumor cells, it is often necessary to Reintroducing tumor-targeting molecules through chemical reactions is not only a complicated and cumbersome process, but also related modification reactions can easily affect the structure and properties of the amphiphilic polymer and its micelles to be prepared.

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