Study On Function Of Mesoporous Selenium,amphiphilic Micelles And Flower-like Gold As Drug Delivery System On Antitumor Activity

Contemporarily,nanomaterials have emerged as a novel platform to revolutionize tumor therapy in personalized biomedical application.Nano-carrier can not only accurately delivery drugs to the tumor site,but also prolong the residence time of drugs,with which could reduce the toxicity of normal tissue.Recent advance of nanomaterials provides new possibilities for the diagnosis and treatment to cancers.Great interest has been paid to gold nanoparticles(AuNPs)in recent years for their attractive properties including the strong and attractive optical properties.AuNPs were also used as nanocarriers for drug delivery.Several strategies have been used to improve AuNPs accumulation in tumor cells specifically and efficient intracellular drug release.Though advances have been made in the research field of AuNPs as TDDS for cancer therapy,more challenges are still confronted.Selenium(Se)is a trace element essential for human health due to its extensive pharmacological actions and physiological functions.Several studies have shown that Se nanoparticles have low toxicity but potent antitumor activity.It is thus not surprising that Se nanoparticles have been used alone or as drug carrier molecules in the prevention and treatment of cancer.For example,multifunctional polyamidoamine-modified selenium nanoparticles dual-delivering siRNA and cisplatin to A549/DDP cells for reversal multidrug resistance.However,low drug loading efficiency,uncontrolled drug release and non-specific targeting properties remain challenges in the application of Se nanoparticles as drug carrier molecules.Polymeric nanoparticle platforms show great potential in diseases treatment,especially for cancer treatment,owing to the biocompatibility,high drug loading efficient,long blood cycle time,easily established surface modification and functionalization.In general,polymer-based nanomedicine can be classified into three classes according to the drug binding mechanism: covalent conjugates,hydrophobic interaction and encapsulated polymers or polymers bubble.Considerable polymers have been approved by the FDA as targeted drug carriers.Enlightened by the investigations,the main objective of these studies is to develop various convenient nano-platform for guiding more efficient and safer cancer therapy.Based on the various nanoparticle systems,the full text is divided into four chapters.This thesis consists of four chapters.In chapter 1,the introduction of the nano-drug-loaded platform and the research progress of the type of nano-drug-loaded stimulation-response.The research methods and progress of enhancing drug delivery to tumor area are introduced.At the same time,we point out the challenges,difficulties and future prospects of the drug delivery system and give the purpose and significance of this thesis.In chapter 2,we now report the first synthesis of mesoporous Se(MSe)and reveal that the MSe nanoparticles have a mesoporous structures based on various measurements such as HRTEM and SRTEM.The novel Se nanoparticles are expected to be drug delivery molecules.DOXorubicin(DOX),a widely used antitumor drug,was used as a model drug,and MSe exhibited a high DOX loading capacity.In addition,we coated the MSe surface with reDOX-sensitive HSA as a gatekeeper to control the release of cargo.The synthesized HSA-MSe@DOX nanoparticles targeted tumor cells through interact with SPARC and released DOX under high glutathione(GSH)conditions.The strategy described in this study may solve some of the problems associated with the use of standard Se nanoparticles.Most importantly,DOX and MSe displayed synergistic effects both in vitro and in vivo,suggesting that HSA-MSe@DOX has potential to be used in cancer therapy.In chapter 3,in this work we optimised the synthesis of nano-sized micelles formulated with different amphiphilic polymers,and loaded Cur into micellar forms and examined their anti-tumor efficacy in vitro and in vivo.The C16-SS-CS-mPEG@Cur anticancer efficacy in recipient mice was evaluated as shown in Scheme1.Our results indicate that C16-SS-CS-mPEG@Cur can be treated inflammatory microenvironment enhanced anti-tumor activity and had fewer side effects in vivo,with potential clinical applications.In chapter 4,as previous reported works,starting with gold nanopaticles as a core,layer-by-layer degradable polymers enable the vectors to delivery the negative gene drugs.However,most of these systems have the limitation in application for in vivo delivery due to high toxicity and low efficacy.In this study,flower-like Au NRs were used as a template for a layer-by-layer strategy to produce a nanoparticle platform modified with a safety and biodegradable polymer chitosan for gene silencing and photothermal therapy.The platform was designed to promote cellular internalization,and induce endosomal/lysosomal escape of siRNA to achieve the down regulation of the protein and mRNA levels.