Anti-tumor Drug-loaded PH–Responsive Polymer Nanocarriers

Many anti-cancer drugs kill or inhibit cancer cells. At the same time, they havehigh toxicity and side effect, leading to limited applications in clinic. For example, theadministered drug dose could not increase due to the problem of tolerance so that thetherapeutic efficiency is not ensured too. Targeted anti-cancer drug carriers become ahot topic in the biomaterial and pharmaceutical fields. In this study, onepH-responsive amphiphilic tri-block polymer and one pH-responsive star-shapedpolymer were designed and synthesized. Their physicochemical properties, drugloading and anti-tumor effect were explored.The amphiphilic triblock copolymer is poly (ε-caprolactone)-poly (N, N-diethylamino-2-ethylmethacrylate)-poly (ethyleneglycol)(mPEG-pDEA-PCL，PDC).The poly (N, N-diethy-lamino-2-ethylmethacrylate)-poly (ethyleneglycol) wassynthesized using atom transfer radical polymerization method. Propynol was used toinitiate the ring-opening polymerization of ε-caprolactone. The click reaction willhappen between them to obtain PDC. The pH-responsive star-shaped polymer waspentaerythritol-poly (ε-caprolactone)-poly (N,N-diethylamino-2-ethylmethacrylate)-poly (ethylene eglycol)(sPCL-PDEA-mPEG， PDPS). The pentaerythritol-poly(ε-caprolactone)(sPCL) was synthesized by the ring-opening polymerization ofε-caprolactone initiated by pentaerythritol. The star-shaped polymer was obtained bythe click reaction conjuncting PDEA with sPCL. The copolymers were characterizedby FT-IR and NMR. The dynamic light scatter and transmission electron microscopyexperiments indicated that the nanocarriers had uniform particles size and were apt toa spherical shape. The changes of the sie and zeta potential under varied pH valuesindicated the pH responsive of the copolymers.The paclitaxel-loaded PDC polymeric micelles were prepared. The paclitaxel orgemcitabine-loaded PDPS polymer nanoparticles were prepared. The encapsulationefficiency and loading efficiency was measured with the HPLC. Drug release wasinvestigated using dialysis method. Under neutral environment, the nanocarriersshowed faster drug release, higher accumulation release. Human breast cancer MCF-7cells was used to evaluate the anti-cancer effect of drug-loaded nanocarriers by MTTmethod.The drug-loaded nanocarriers showed better anti-cancer effect in the low pHmedia (pH6.5). The Kunming mice models with hepatocellular carcinoma were established to evaluate the anti-cancer effect in vivo. It was denmonstrated that thedrug-loaded nanoparticles exhibited comparable activity in anti-cancer effect as freepaclitaxel and decreased the toxicity of paclitaxel. The pH responsive copolymermicells and the pH responsive star-shaped polymers nanoparticles are promisinganti-cancer drug carries.