Preparation Of Functional Polymer Nanocapsules Based On Covalent Self-assembly

Polymer nanocapsules are gifted with many unique properties compared with other vesicles.Thus,they are attracting more and more attention from chemists.After nearly 70 years of research efforts,remarkable achievements have been acquired in the polymer nanocapsules field and a variety of polymer-based nanocapsules have been developed.However,the creation of new synthetic methods for polymer-based nanocapsules and the expansion of their applications are still the focus for chemists.The “Covalent self-assembly through irreversible covalent formation” concept to construct single molecular layer polymer nanocapsules has attracted intense scientific and technological attention.The new system containing the remarkable features of single moluecular layer polymer nanocapsules include: facile,non-templates or non-preorganized;high structural stability.More important,an outstanding feature of this method is that the single-molecular-thick polymer shell,which comprises functionalized macrocyclic host molecules,such as cucurbit[n]urils,allows facile tailoring of its surface properties in a noncovalent manner by virtue of the unique host-guest chemistry of the accessible molecular cavities exposed on the surface.Inspired by this success,recently,so many attentions have heen paied to prepared new single moluecular layer polymer nanocapsules through convalent self-assembly.While,it requires the building blocks be rigid,flat molecules with multiple functional groups at the periphery,which can be directly linked into two dimensional polymers by flexible linkers.So,constructing these kinds of molucules as building block is not an easy task,especially using macrocyclic host molecules as building blocks to fabricate high-performance 2D polymer materials by covalent self-assembly.On the other hand,as a novel method for fabricating two-dimensional polymers,covalent self-assembly still remains further explored in many aspects,for example,can all the flat and rigid monomers with symmetrical groups be used for covalent self-assembly? And how to further functionalize the assemblies?Pilararenes are new type of macrocyclic host molecules,beyond their excellent host-guest property,pillararene based functionalization also attracts various attentions.While,in previous,people always decorate it up and down rims,few attentions has been given to its lateral site,the methyl bridge.Indeed,functionalization at its lateral site is meaningful,because it can be as new building block for covalent self assembly after lateral decoration.Taking all of these into consideration,we report a facile synthesis of lateral modificated pillar[5]arene derivative for the first time through bromination reaction at methylene bridge of the dimethoxypillar[5]arene to generate methylene-bridge brominated pillar[5]arene(BDMP5).The lateral homogeneous distribution of the reactive groups makes BDMP5 as the new building block to covalently self-assemble into polymer nanocapsules.The novel polymer nanocapsules have many advantages compared with those traditional ones.For example,that they are easily prepared without any template,besides,the shell contains thin single layer and composed of multiple pillararenes which can capture guest molecules by host-guest interactions.Additionally,the new nanocapsules can be facilly developed as an excellent platform for a wide range of applications,such as efficient drug delivery sysyem,high HRP enzyme mimics.The details are as follows:1.Preparation of lateral cross linked pillar[5]arene based polymer nanocapsules by covalently self-assembly A lateral functionalized pillar[5]arene is synthesized for the first time through bromination reaction at methylene bridge of the dimethoxypillar[5]arene.We have used BDMP5 as building block to covalently self-assemble into polymer nanocapsules.The novel polymer nanocapsules have many advantages compared with those traditional ones.For example,they are easily prepared without any template.Besides,the shell is very thin and composed of multiple lateral covalent cross-linked pillararenes which can capture guest molecules by host-guest property.2.Reductive-Responsive Single Molecular Layer Polymer Nanocapsules Prepared by Lateral Functionalized Pillar[5]arenes for Targeting Anticancer Drug Delivery Nanocapsules can be extensively applied on drug delivery,compound sepration,disease diagnosis,chemical catalysis,bio-imaging and food additives.The typical approaches for synthesis of nanocapsules include template synthesis,self-assembly,emusion polymerization etc.Based on the work done in part 1,we continued to present a similar method for preparation of polymer nanocapsules through covalent self assembly.Herein,a new kind of reduction-sensitive,biocompatible pillar[5]arene-based single molecular layer polymer nanocapsules are developed.taking advantages of the structures features of the nanocapsule shell that composed of host macromolecules,the new system is decorated with functional tumor-penetrating peptide by host-guest manner.Thus successfully developing it as a new target smart vehicle for efficent drug delivery.The novel smart vehicles possess stable structures,can encapsulate cargoes and degrade quickly under reduction-stimuli,and more importantly this system displays very low cytotoxicity,excellent target recognition,high penetration and inhibition for tumor cells.After all,this new kind of vehicle not only provides a good platform for cancer therapy,but also extends the design of smart multifunctional materials for biomedical applications.3.Diselenium-containing Ultrathin Polymer Nanocapsules Prepared by Lateral Functionalized Pillar[5]arenes: A Highly Efficient Targeting Drug Delivery Nanocarrier for Combining Anticancer Selenium plays an essential role for human health.Developing selenium containing biomaterials is a fascinating task.It not only broadens the research of selenium chemistry,but also extends the design of selenium containing materials for biomedical applications.Pillar[n]arenes are a new and important class of macrocyclic hosts,and pillararene-based biomaterials have played an important role in bioimaging,drug delivery and controlled release because of their unique properties.Combination of selenium and pillararenes to prepare selenium-containing pillararene-based biomaterials is also of great significance for developing biomedicine.Herein,we use diselenium bond bridged diamine as linker,by cross-linking with BDMP5 through covalent self-assembly strategy,we successfully developed a new kind of diselenium containing pillar[5]arene-based ultrathin polymer nanocapsules.The new system exhibits a very potent anticancer effect;the incorporation of the cleavable redox diselenium bond into polymer nanocapsules provides a smart nanocarrier for drug delivery.Moreover,the polymer nanocapsule has been developed as an anticancer drug targeting delivery by loading anticancer drug and introducing tumor-penetrating peptide RGD through host-guest interaction strategy.The targeting DOX-loaded diselenium-containing polymer nanocapsules possess enhanced stability,targeting delivery and release,cell internalization,and tumor accumulation,resulting in an effective combining inhibition for tumor progression.Thus,diselenium-containing pillar[5]arene-based ultrathin polymer nanocapsules can be potentially used as a new anticancer drug vehicle to encapsulate other hydrophobic anticancer drugs for combining anticancer.4.Frame-guided covalent self-assembly strategy to prepare bilayered ultrathin polyer nanocapsules: a new platform for peroxidase mimics Bilayer or multilayer capsules,consisting of two or more layers of self-assembled molecules,have received enormous attention in the field of biophysical research because they provide an opportunity to development of biomimetic systems,pharmaceutical carriers,nanoreactor,and imaging.Herein,we use lateral cross linked pillar[5]arene based polymer nanocapsules as templete frame,by taking advantages of the structures features of the nanocapsule shell that composed of host macromolecules,the out shell of capsules are decorated with functional molecules with one hand containg guest molecule to bind with pillararenes and the other hand being pyridine group to complex with Iron porphyrin derivatives.When we add allyl iron porphyrin derivatives to(Feppy)the solution,it can disperse at the surface of the polymer capsules by binding with pyridine group.Then,we continue to add linkers to cross link with Feppy,it can form a new layer of polymer nanocapsules at the surface of template nanocapsules.Due to the shell mainly composed of iron-porphyrins and nearly one monomer thick,the peroxidase mimic constructed here had the advantages of rapid mass transfer,high catalytic activity and good substrate affinity.Based on the peroxidase-like activity of the covalently assembled nanocapsules,a highly sensitive colorimetric sensor for glucose was fabricated.