Design And Synthesis Of Light-Sensitive O-Nitro Benzaldehyde-Based Polyacetal For Drug Delivery

Recently,stimuli-responsive polymers have attracted more and more attention.These polymers are wildly used as carrier for drug delivery,typically for targeted cancer therapy due to its well control-release profile by some stimuli,such as light,p H,temperature,enzyme and redox.In this thesis,we mainly designed and synthesized two different types of o-Nitrobenzaldehyde-based acetal containing monomers and their corresponding polyacetals,and studied its self-assemble behavior,drug loading and drug release properties upon UV light.Firstly,a new cyclic acetal containg acrylate monomer,5-methyl-2-(2-Nitrophenyl)-1,3-dioxan-5-yl)methylmethacrylate(MNDMMA)was designed and synthesized successfully.With this monomer,an amphiphilic block copolymer m PEG-b-poly(MNDMMA)was synthesized using m PEG-Br as macro-initiator by atom transfer radical polymerization(ATRP).The amphiphilic copolymer can be self-assembled in aqueous solution to form particle with 50-100 nm diameter and narrow polydispersity by dynamic light scattering(DLS).And the particle size will increased upon 365 nm UV light.For example,97.2% of particle size is 58 nm before UV light irradiation and 36% 58 nm with 60% 193 nm after UV light.We then investigated the release in aqueous solution of a model hydrophobic guest,Nile Red(NR),loaded in the nanoparticles upon UV disintegration of the nanoparticle core.The fluorescence emission spectra of NR loaded in the particle before and after short time UV 365 nm irradiation shows the emission intensity of NR loaded particle is strong at 550 nm and drops gradually with in creasing irradiation time.That means NR can be control-release well from particle by UV light irradiation.Considering the acetal structure of monomer,we proposed this monomer also has the acid degradable property.Unexpectely,the monomer could not degrade even in p H1 aqueous solution.The reason is that the cyclic acetal and benzyl group increase the stability of acetal group in acid solution.To further discover new UV/p H dual responsive monomers,we designed and synthesized a new non-cyclic acetalmonomer,1-(bis(2-azidoethoxy)methyl)-2-Nitrobenzene(AMNOB).This diazide monomer was polymerized with dialkyne monomer 3,3-thiodipropionate dipropyl-ynyl ester by Cu AAC “click chemistry” to form a linear polymer.We studied its degradable properties upon UV,acid,and dithiothreitol(DTT)respectively.The results showed the polymer was degraded into small molecules by GPC characterization after treated UV 365 nm irradiation for 10 min,p H 5.5 PBS solution for 1 h and 10 mg DTT for 1 h respectively.That means the polymer has UV/p H/DTT triple responsive property.