Study On The MR Imaging/Drug Loaded Multi-Functional Microspheres With Tumor Environmental Sensitivity

Polymer/inorganic composite microspheres have been widely concerned in biomedical field because of their advantages in both polymer microsphere and inorganic nanomaterials.In the composite microspheres,inorganic nanomaterials provide special properties of magnetism or optoelectronics;on the other hand,polymer microspheres play roles of carriers,and also provide multifunctional groups for their further coupling of biological enzymes,antibodies,drugs,and other chemical modifications.This paper designed a self-assembly approach to construct a novel polymer/magnetic nanoparticle hybrid microspheres with pH/trypsin dual sensitivity.In this way,Doxorubicin-loaded magnetic nanoparticles?MNPs-DOX?were preparation,and on this basis,magnetic composite microspheres were prepared via a self-assembly method with MNPs-DOX and poly-L-lysine?PLL?.In this work,we focused on the praperation,MR imaging enhancement and environment-sensitive drug release of MNPs-DOX and the PLL/MNPs-DOX composite microspheres,and the contributions are as follows.Firstly,polyacrylic Acid?MNPs-PAA?stabilized Fe₃O₄ nanoparticles?MNPs?which had mean diameter of 10 nm and superparamagnetism capped with were synthesized through a solvothermal method.On this basis,doxorubicin was loaded onto the magnetic nanoparticles?MNPs-DOX?by a pH-sensitive hydrazone bond.In MR imaging,MNPs-DOX showed good T₂ contrast enhancement capability,at the same time,the DOX conjugated by hydrazone bonding enables the MNPs-DOX to release DOX in acidic environment,which means MNPs-DOX have good environmental responsiveness.On this basis,we also fabricated PLL/MNPs-DOX composite microspheres through a self-assembly method,which is stable in aqueous solution.The size of the composite microspheres are adjustable at the range of around 150²50 nm by changing the concertration of PLL in the self-assembly.With superparamagnetism,PLL/MNPs-DOX composite microspheres showed much higher T₂ contrast enhancement capability in MR imaging than that of MNPs-DOX,its T₂ relaxation rate was up to96.1mM^-1s^-1.In vitro drug release experiment showed that the composite microspheres underwent accelerated DOX release behavior if were treated by tryptic and acidic environment This result leads to the conclusion that composite microspheres with pH and trypsin dual-responsive DOX release capability.In consideration of the excellent MR imaging enhancement and pH/trypsin dual responsive ability of the PLL/MNPs-DOX composite microspheres,they are of greatpotential in the application ofbio medical diagnosis and trerapy.