The invention relates to a hypoxia targeting
hyaluronic acid nano
delivery system and a construction method and application thereof, the construction method comprises the following preparation method: S1, dissolving 2-
nitroimidazole and K2CO3 in
dimethylformamide, carrying out high temperature alkali treatment, adding N-Boc-bromoethylamine, and carrying out high temperature reaction to obtain Boc-NIH; s2, dissolving the Boc-2-NIH in
dichloromethane, adding
trifluoroacetic acid for deprotection, and adjusting the pH value to be neutral, so as to obtain 2-NIH; s3, dissolving HA in deionized water, sequentially adding EDC and NHS to activate carboxyl, then adding 2-NIH, reacting at
room temperature, and dialyzing to obtain a hypoxic targeting
hyaluronic acid nano delivery carrier HA-NIH; s4, HA-NIH loads a
drug, and the hypoxia targeted
hyaluronic acid nano
delivery system is formed. According to the invention, a
bifunctional nano
system with CD44 active targeting and
hypoxia response release is successfully constructed, a dynamic regulation and control mechanism of HA molecular weight on a targeting-
permeation-retention effect is provided, and a synergistic effect of
tumor stem cell microenvironment specific response and
drug space-time release is realized.