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Preparation Of Injectable Responsive Hydrogel Anti-Tumour System And Its Application

Posted on:2023-08-19Degree:MasterType:Thesis
Country:ChinaCandidate:Y J KongFull Text:PDF
GTID:2531306836475134Subject:Optical engineering
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Cancer is one of the major threats to human health and is commonly treated by chemotherapy,radiotherapy and surgery.However,these traditional treatments have certain limitations,such as the tendency of recurrence,poor treatment effect and side effects.In order to improve the cure rate of cancer,researchers have developed various treatment techniques,such as photothermal therapy,photodynamic therapy,chemodynamic therapy and immunotherapy,and some other new treatment methods have been developed.In order to improve the therapeutic effect of chemotherapy and reduce the toxic side effects,the sustained and controlled release of drugs has become an urgent problem for oncology chemotherapy.Various drug carriers,such as nano/microspheres,nanoparticles,liposomes,etc.,have been designed for use in various cancer therapies and even combination therapies.However,as nanoparticles have certain drawbacks such as low therapeutic accuracy,short in vivo retention time and poor biocompatibility,better drug carriers need to be designed and researched to solve the above problems.As one of the drug carriers,hydrogels have been widely studied for their advantages of long-term drug accumulation and release at the tumour site,low systemic drug toxicity and controlled drug release.Hydrogels have a three-dimensional cross-linked network structure and can effectively load drugs.However,conventional hydrogels have the disadvantages of requiring surgical implantation,large traumatic surface and uncontrolled drug release for tumour treatment.Therefore,injectable smart-responsive hydrogels have attracted a lot of interest from researchers.Thus,the development of smart responsive hydrogels offers a new direction for cancer treatment.In this thesis,two injectable smart-responsive nanoparticle-hydrogel drug delivery systems are designed,with the following main research elements.1.An alternative injectable hydrogel for photothermal/chemotherapy of pancreatic cancer based on a thermosensitive liposome-hydrogel(Lip-Gel)system.This system prolongs the retention time of chemotherapeutic drugs(GEM)in the tumour tissue and improves the phagocytosis of the drugs by tumour cells,thus enhancing the therapeutic effect.The NIR-II small molecule photothermal reagent(DPP-BTz)and the chemotherapeutic drug(GEM)are first encapsulated in thermosensitive liposomes,which are then mixed with a hydrogel precursor solution to obtain a liposome-hydrogel(Lip-Gel)precursor solution.After injection into the tumour site,the precursor solution is able to transform into a gel structure at physiological temperature and the DPP-BTz it carries inside generates heat under 1064 nm laser irradiation,causing the thermosensitive liposomes to rupture,thereby releasing the GEM drug and killing the tumour cells.The hydrogel system has good biocompatibility,in situ hydrogel formation,and NIR-II photothermal controlled GEM release,and can effectively treat pancreatic cancer by NIR-II photothermal and chemotherapeutic effects.2.Combining targeted nanopharmaceutical particles with photothermally responsive hydrogels for combined photothermal-chemotherapy treatment to enhance antitumour therapy.A photothermal small molecule reagent(ICG)is first combined with a chemotherapeutic drug(MTX)by self-assembly to form targeted nanodrug particles(ICG-MTX).ICG-MTX is then mixed with a hydrogel precursor and a thermosensitive radical initiator to obtain a hydrogel precursor solution.The precursor solution releases alkyl radicals under the effect of light and heat,which induces the conversion of the precursor solution from liquid to gel(sol-gel),allowing the nanodrug to be effectively retained in the vicinity of the tumour tissue for sustained release of the chemotherapeutic drug.Due to the targeted nature of MTX,the released nanodrug particles can be targeted to tumour cells,further enhancing the precision of the treatment.The results show that this injectable nanodrug-hydrogel system has good therapeutic efficacy against tumours.
Keywords/Search Tags:Injectable, Responsive, Hydrogel, Nanomedicines, NIR, Photothermal Therapy, Chemotherapy, Liposomes, Self-assembly
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