PH And Reduction-Responsive Nanoparticles For Intracellular Drug Delivery

In recent years,the use of nanocarriers for drug delivery has become an effective method and research hotspot for anti-tumor therapy.Drug delivery nanocarriers using only chemotherapeutic agents can greatly extend the half-life in the blood,but also it is possible to maximize the accumuLation of dose at the site of the lesion by enhancing the permeability and retention?EPR?effect,and to a great extent reduce the damage to normal tissues and organs.At present,commonly used nano drug carriers include liposomes,nanocomposites,inorganic nanospheres,drug-polymer conjugates,polymer micelle polymer conjugates,and polymer micelles.Among them,polyionic complex micelles?PICs?are nanocarriers formed by a group of polymers having opposite charges through electrostatic interactions,and have attracted widespread attention in the field of drug delivery in recent years.For example,Kataoka et al.studied systematically polyaniline-based PIC micelles and applied them to DNA,RNA,and protein drug delivery.Zhang Xi et al.prepared a series of PIC micelles based on"super amphiphilic self-assembly"by combining an amphiphilic block polymer and a small molecuLe surfactant with a counter charge.The obtained PIC micelles also have the characteristics of enzyme,uLtraviolet light and H₂O₂ oxidation response,and can be used as intelligent drug delivery carriers.The first part of this paper describes a PIC micelle made from PEG monomethyl ether-polylysine block copolymer and small molecu Le 2,2'-dithiodisuccinic acid.The particle size is 65-75nm and has a narrow particle size distribution.In the second part of this article,a simple chemical method was used to construct a PEG-based monomethyl ether-acetalized dextran nanoparticles?AC-DEX NPs?and used as pH and reductive dual-response drug delivery.system.The in vitro cytotoxicity assay showed that the obtained PIC micelles and AC-DEX NPs all showed good biocompatibility,and couLd maintain a stable nanoparticle structure in water and saline.Doxorubicin?DOX?was further used as a model drug,which was entrapped in PIC micelles and AC-DEX NPs.The resuLting drug-loaded PIC micelles and AC-DEX NPs have dual pH-and GSH-responsive drug release properties,DOX release can be accelerated at low pH and high GSH concentrations.Flow cytometry and laser confocal microscopy demonstrated that both drug-loaded nanoparticles can be efficiently endocytosed by MCF-7 tumor cells and achieve efficient intracelluLar drug release.Finally,MTT assays showed that both drug-loaded nanoparticles exhibited strong cell proliferation inhibition on MCF-7 tumor cells,and their IC₅₀ was similar to DOX pure drug.In summary,our prepared PIC micelles and AC-DEX NPs are expected to be used as intracelluLar drug delivery vehicles and have potential applications in cancer chemotherapy.