Monoclonal Antibody-conjugated Polyphosphoester-hyd-DOX Prodrug Nanoparticles for Targeted Chemotherapy of Liver Cancer Cells

In order to overcome the limitation of traditional active nano-therapeutic drugs on tumor targeting efficiency which cannot reach the receptor/target in sufficient amount in the body,in this work,we developed a monoclonal antibody(mAb)and a polymer-hyd-doxorubicin prodrug conjugate,which enables the self-assembled nanoparticles to have precise targeting,tumor tissue aggregation and pH-sensitive drug release.We first prepared an amphiphilic polymer prodrug,abbreviated as H2N-PEEP-b-PBYP-hyd-DOX,via a combination of ring-opening polymerization(ROP)and"click"chemistry,in which PEEP and PBYP represent two kinds of phosphoester segmemts,-hyd-is hydrazone bond.After self-assembly into prodrug nanoparticles(PDNPs)with a diameter of about 93 nm,CD147 mAb was conjugated onto the PDNPs by EDC/NHS chemistry to form mAb-PDNPs.For the PDNPs and mAb-PDNPs,we also investigated their stability,in vitro drug release behavior and cellular uptake.The results showed that the pH-responsive PDNPs can remain relatively stable under the condition of PB 7.4 buffer solution.However,under acidic conditions or in the presence of phosphodiesterase I(PDE I),both the amount and rate of DOX release increased at the same incubation period.Cytotoxicity assay showed that mAb-PDNPs exhibited higher cytotoxicity(IC50:1.12 mg·L^(-1))against HepG2 cells than PDNPs(IC50:2.62 mg·L^(-1))without monoclonal antibody.The nanoparticles with antibodies mAb-PDNPs have relatively better stability and can directly achieve the targeting drug delivery through CD147 mAb.

Polyphosphoester-modified Cellulose Nanocrystals for Stabilizing Pickering Emulsion Polymerization of Styrene

The structure and properties of functional nanoparticles are important for stabilizing Pickering emulsion polymerization.Recently,cellulose nanocrystals(CNCs)are increasingly favored as a bio-based stabilizer for Pickering emulsions.In this study,we reported a novel functionalized polyphosphoester-grafted CNCs for the stabilization of oil-in-water Pickering emulsions and the emulsion polymerization of styrene.First,polyphosphoester containing an amino group at one end of the chain,abbreviated as PBYP-NH2,was prepared by ring-opening polymerization(ROP)and hydrolysis reaction,wherein PBYP represents poly[2-(but-3-yn-1-yloxy)-2-oxo-1,3,2-dioxaphospholane].Subsequently,CNC-COOH was obtained via 2,2,6,6-tetramethylpiperidine-1-oxyl(TEMPO)oxidation of CNCs.The functionalized nanocrystals CNC-PBYP-COOH with carboxyl groups and polyphosphoester on the surface were obtained by the amidation reaction of PBYP-NH2 with CNC-COOH.Finally,we used CNC-PBYP-COOH as sole particle emulsifiers to stabilize styrene-in-water Pickering emulsions and studied its effects on the emulsions in details by using dynamic light scattering(DLS).The results indicated that the properties of these emulsions depended on the concentration of hydrophobically modified CNCs,volume ratios of oil to water,and pH values.The modified CNCs had higher ability to stabilize the styrene-in-water emulsions relative to the unmodified CNCs,and a stable oil-in-water(o/w)Pickering emulsion with diameter of hundreds of nanometers could be obtained.The resulting emulsions could be polymerized to yield nanosized latexes.The polyphosphoester-modified CNCs as green particle emulsifiers can efficiently stabilize nanoemulsions and latexes,which would promote the development of novel environmentally friendly materials.