| Cancer is one of the most deadly diseases in China.At present,the most common methods of cancer treatment include three categories: surgical treatment,chemotherapy,and radiotherapy.Among them,surgical treatment has some problems,such as high risk,large trauma area and easy recurrence;while radiotherapy and chemotherapy kills cancer cells,they also damage the normal cells of the body,resulting in damage to the normal physiological function of the human body.Therefore,there is an urgent need to develop new types of cancer diagnosis and treatment strategies.In recent years,protein drugs have been widely developed and applied in cancer treatment based on their advantages of high therapeutic efficiency and low toxicity and side effects,and have shown great clinical application prospects.Up to now,protein drugs usually act on extracellular targets and reduce the therapeutic efficiency.Therefore,how to break through the membrane barrier and effectively deliver protein drugs to the tumor cytoplasm has become the key for protein to be used in cancer therapy.To solve these problems,researchers have developed a variety of multi-functional drug delivery systems.For example,a strategy combined with nanomaterials and nanotechnology is used to efficiently encapsulate in polymer nanocarriers,enabling protein drugs to extend blood circulation time and enhance targeted tumor aggregation.Polypeptide or hyaluronic acid materials have been widely used in the preparation of polypeptide nanocarriers because of their good biodegradability and biocompatibility.Moreover,hyaluronic acid nanocarriers can also improve the specificity of drugs to lesions by combining with biological targeting materials;surface modification of polypeptide nanocarriers also contributes to cell uptake,which further prolongs the effective action time of drugs and enhances the therapeutic effect.Relative to traditional chemotherapy,this treatment with good stability,sustained,effectiveness and targeted is greatly reduced,thus reducing the side effects and cost in the process of treatment.In this paper,according to the difference between microenvironment inside and outside tumor cells,we designed two kinds of hypoxia-sensitive polymer nano-drug delivery carriers based on polypeptide and hyaluronic acid,and evaluated their drug delivery performance and cancer-killing effect.First,we prepared an amphiphilic polymer bearing hypoxia-sensitive derivatives,which was used to promote self-assembly as nanocarriers for delivery of CC to cancer cells.This nanocarrier was fabricated with m PEG as the hydrophilic shell to inhibit the adsorption of blood proteins in the blood circulation,while bearing nitroaromatics as the hydrophobic block to enhance system stability and endow the tumor cell with hypoxia sensitivity.The experiments showed that the polymeric micelles possess good stability and biocompatibility,the drug loading rate was 92%,and could kill 70% of HCC cells in hypoxic environment.Secondly,we also prepared a hypoxic-responsive hyaluronic acid nanogel for enhanced photodynamic therapy.Using PEGylated decorated hyaluronic acid as polymer template,it has the ability of active targeting of CD44 and good stability.At the same time,the azo group with hypoxia sensitivity was selected as the cross-linking agent,experiments showed that the nanogel,with a size of about 169 nm,could be used as a promising carrier to enhance the singlet oxygen production efficiency of photosensitizers in tumor cells.Finally,we found that nanocarriers with good biocompatibility,high loading rates and controlled release can be used to effectively deliver anticancer drugs to enhance cancer treatment. |
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