Construction And Application Of Dopamine–containing Polymer Nanomaterials

Up to now,the use of anti-cancer drugs is one of the main methods for the treatment of malignant tumors.For chemotherapeutic agents,their low solubility in water,poor biodistribution and no specificity to cancer cells seriously reduce their anticancer activity.Drug delivery systems are expected to address the above-mentioned drawbacks of chemoterapeutic angents.Therefore,two different drug delivery systems with multifunctional responsiveness have been fabricated to deliver chemotherapeutic agents and reduce their side effects in cancer treatment.Polydopamine that contains functional groups such as imine,amine,and catechol can be combined with a variety of chemotherapeutic agents to achieve their drug loading and delivery.Therefore,this paper focuses on the construction of polymer-based drug delivery systems and their application in cancer treatment.The specific study are as follows:1.Two block copolymers with different stuctures(CH₃O–PEG₄₃–b–PAA₈₈ and PAA₇₂–b–PEG₄₃–b–PAA₇₂)are designed and synthesized through atom transfer radical polymerization（ATRP）.The results show that these copolymers can self–assemble into two different polymeric assemblies,depending on the choice of polymer structure.In this self–assembly process,the polymerization of dopamine and the coupling between polydopamine and block copolymer are performed for succession（denoted as polymerization–coupling process）,which synergistically induces the self–assembly of block copolymer to yield ordered structures,including micelles and vesicles.While the other key to this strategy is to exploit the self–polymerization of dopamine that results in polymeric vesicles with cross–linking structure and enhances their stability without additional cross–linking agents.These polymeric vesicles exhibit an ideal drug loading capacity toward doxorubicin（DOX）and bortezomib（BTZ）because of a number of carboxyl groups,conjugated system,and catechol moieties.While drug–loaded polymeric vesicles are sensitive to endogenous weak acidic microenvironment to unloaded drug,fulfilling their drug delivery.Therefore,this strategy provides new insights into the development of molecular self–assembly,and resultant polymeric assemblies show directly potential application in the field of drug delivery.2.A polymer carrier P（MAA–co–PEGMA–co–DAA）_BACy（PMPDB）combining catechol groups,disulfide crosslinked structures and carboxyl groups was prepared by microemulsion polymerization.The pendent carboxyl within polymeric carrier was exploited to absorb DOX through electrostatic interaction,and the catechol moietie within polymeric carrier was exploited to conjugate BTZ through the formation of boronate bester.Both electrostatic interaction and boronate bester are stable in neutral or alkaline p H,while they are instable in acidic environment to further recover the activity of BTZ and DOX to cancer cells.The experiments in vitro verified this dual–drug delivery system has the following advantages:（1）it possess a superior stability to prevent the premature leakage of the as–loaded drug in physiological environment to inhibit the multidrug resistance;（2）its structure could be destroyed depending on the typical endogenous stimulus such as slightly acidic p H or elevated GSH level to quickly release the as–loaded drug for increasing efficacy against tumor cells.The presented research,therefore,suggests a design for GSH-responsive degradable polymeric carriers for joint delivery of active chemotherapeutics in a p H-sensitive manner,showing a potential application in the future of cancer treatment.