Construction Of Nano-delivery System Based On Supermolecule Self-assembly For Antitumor Drug Delivery

According to the world health organization?WHO?,about tens of millions of people worldwide are diagnosed with cancer each year,and more than half of them dying of this disease.With the progress of science and the development of cancer treatment,there are more and more new cancer treatments other than traditional treatments,such as targeted therapy,immune therapy and gene therapy,etc.However,in these treatments,chemotherapy is still the main method of cancer treatment.Nano drug delivery system?NDDS?can manage drug compounds and improve the effect of drug treatment.What's more,nano-drug delivery system?NDDS?can solve the problems of poor solubility of drugs,low bioavailability and non-specific distribution in vivo.In recent years,scientists have spent great effort to study the stimulate response model of nanometer materials used in drug delivery system and to make the drug carrier response to endogenous or exogenous stimuli releasimg drugs in a particular organization effectively.Supramolecular chemistry is an organized complex entity that held two or more chemical species together by intermolecular forces.Supramolecular amphiphiles is constructed based on noncovalent bonds include hydrogen bond,hydrophobic interaction and coordination function,which has developed into a new type of building blocks,mainly through multistage self-assembly supramolecular structure.The interaction between host and guest is considered to be a very important method to build supramolecular amphiphiles.The self-assembly of host-guest superamphiphiles can provide not only for structural versatility but also for functional modulation of nanomaterials for the easy introduction of chemical moieties on host or guest molecules that would provide an important tool to functionalize the self-assembled nanostructures.This paper mainly desined stimulus responsive supramolecular amphiphiles through host and guest interaction between?-CD and ferrocene,and we further studied the properties of the nanoparticles self-assembled through the supramolecular amphiphiles.The specific contents includes:?1?The supramolecular amphiphiles MH₄-?-CD-AcMH were prepared based on the interaction between?-CD and ferrocene.The combination of the pH-sensitive covalent acetal group and the oxidation-sensitive noncovalent host-guest interaction of?-CD and ferrocene providedtheobtainedfullyoligosaccharide-basedsupramolecularamphiphiles multi-responsiveness and could respond to the intracellular microenvironment.The amphiphiles could self-assemble to form spherical supramolecular nanoparticles to provide efficient drug delivery platforms.Under the acidic conditions of lysosomes,the acetal structure of hydrophobic segment breaks down causing maltoheptaose from hydrophobic to hydrophilic and releasing doxorubicin?DOX?wrapped in it.Under oxidative condition,the electrically neutral ferrocene left the cavity of?-CD following their transformation into ferricinium ions that leading to nanoparticle disolution and releasing doxorubicin?DOX?.The particle size of nanoparticles was observed about 40 nm by TEM photograph;and the cytotoxicity results showed that the drug-loaded nanoparticles had a strong effect on human colorectal adenocarcinoma cells?SW620?;the fluorescence experiment showed that SW620 cells had a good endocytosis effect on nanoparticles.The nano-drug delivery system prepared by supramolecular self-assembly could provides a more concise method for the preparation of multiply responsive drug carriers.?2?The supramolecular amphiphiles PEG-?-CD-CA were prepared based on the interaction between?-CD and ferrocene.PEG can be used as a hydrophilic segment of a micelle,and ferrocene modified cinnamaldehyde Prodrug can act as hydrophobic section of a micelle.The acetal linkage equiped the supramolecular amphiphiles with acid sensitive property that cold respond to the intracellular microenvironment.Under the acidic conditions of lysosomes,the pH-sensitive acetal bond breaks down and releases cinnamaldehyde that induce hydrogen peroxide?H₂O₂?production.The hydrogen peroxide?H₂O₂?was catalyzed by ferrocene via Fenton reaction to form hydroxyl radicals?·OH?leading to cell apoptosis.The nano-drug delivery system prepared by supramolecular self-assembly could provides a more concise method for the preparation of acid sensitive drug carriers.