Preparation Of Polyester-Based Two-Dimensional Platelet Micelles By Living Crystallization-Driven Self-Assembly And The Application In Drug Delivery

Living crystallization-driven self-assembly（CDSA）is a controllable self-assembly technology dominated by the crystallization of crystalline block copolymers（BCPs）.It has been proved to be a powerful tool for creating one-dimensional（1D）or two-dimensional（2D）nanomaterials.This bottom-up self-assembly technology can accurately control the size and composition of the prepared materials.At present,2D materials have gradually become a research hotspot due to their unique physical and chemical properties,but the development and application of 2D systems with precise control of size and composition remain a huge challenge.In this work,CDSA was introduced into the BCP system containing poly（p-dioxane）（PPDO）,and impressive 2D platelet micelles were successfully prepared through the regulations of a series of crystallization conditions.In addition,based on the previous work of our group,2D pH-responsive crystalline platelet micelles were designed and this biocompatible poly（ε-caprolactone）（PCL）platelet micelles with low dispersion and precise component regulation were applied to the field of stimulus-response drug delivery for the first time.The specific work of this paper is as follows:1.In the first part,PPDO homopolymer,a series of PPDO₂₂-b-PDMA_n BCP with different block ratios（corona/core）（subscript n represents the degree of polymerization of PDMA block,n=133,154,205,286）（PDMA=poly（N,N-dimethyl acrylamide））,and PPDO₂₂-b-P4VP₁₃₂（P4VP=poly（4-vinylprydine））BCP were synthesized by ring-opening polymerization and reversible addition-fragmentation chain transfer（RAFT）polymerization.Then,taking PPDO₂₂-b-PDMA₁₃₃ as an example,we proved that the insufficient size control of 2D PPDO platelets could be overcome through modulation of solvent compositions or elevating the crystallization temperatures for PPDO.The possible mechanism involves an improved unimer solubility that avoids fast unimer aggregation.As a result,uniform 2D platelet micelles with a controlled area over a substantial size range are created via the further growth of the unimer.In addition,the shape control of 2D platelet micelles from quasi-square to hexagon to lozenge shapes can be accessible by regulating the crystallization conditions such as adding different amounts of cosolvents or crystallization at an elevated temperature.Meanwhile,spatially defined block comicelles can be achieved via the seeded growth approach from PPDO core-forming BCPs with different corona functionalities at elevated temperatures.Finally,dialysis and cell experiments have demonstrated that 2D PPDO platelet micelles own excellent water stability and biocompatibility.2.In the second part,based on the successful synthesis of polymers,four types of2D hexagonal platelet micelles with tailored compositions and tunable size can be obtained by using seeded growth approach.The component of four biocompatible 2D platelets include a crystalline PCL core,a hydrophobic P4VP segment or a water dispersible PDMA block in ethanol（Et OH）.In addition,transferring those uniform platelets with tailored compositions to an aqueous solution in the presence of a hydrophobic drug leads to efficient encapsulation of the cargo in the P4VP segments via hydrophobic interactions.These drug-loaded platelets exhibit pH-responsive release behavior in aqueous media due to the protonated-deprotonated process of P4VP blocks in acidic and neutral solutions.