Tumor Microenvironment-Responsive Polydopamine-Based Core/Shell Nanoplatform For Synergetic Theranostics

At present,cancer is still one of the major diseases threatening human health.Traditional cancer treatments have a low cure rate and high risk of recurrence,so many new treatments are emerging.However,the efficiency of single treatment is still limited.The synergistic treatment strategy can make up for the deficiency of single treatment and achieve complementary advantages.Based on this,a polydopamine-based theranostic nanoparticles?PDA@TA-Fe?was constructed for T₁/T₂-weighted MR imaging-guided synergistic tumor treatment of CDT/PTT.Polydopamine?PDA?was prepared through the oxidation and self-polymerization of dopamine monomer under the alkaline condition.Tannic acid?TA?as a natural phenol can be used as organic ligand to coordinate with Fe³⁺to form a TA-Fe cross-linked shell of TA-Fe,which attached to the PDA surface.The obtained PDA@TA-Fe possessed a spherical core-shell structure,uniform particle size and excellent dispersibility.Due to the five outer unpaired electrons of Fe³⁺and its intrinsic magnetic properties,PDA@TA-Fe exhibited excellent longitudinal and transverse relaxivity values(r₁=5.90 mM^-11 s^-1,r₂=41.35 mM^-11 s^-1).After the intravenous injection of PDA@TA-Fe for 24 h,a brightening effect was clearly exhibited in the T₁-weighted image,and the tumor signal intensity increased by 177%.Concurrently,the obvious dark T₂-weighted signal enhancement occurred at the tumor site,in which the signal intensity reduced by 53%within 24 h.The PDA@TA-Fe showed excellent photothermal effect and the photothermal conversion efficiency at 808 nm and 1064nm was 29%and 41%,respectively.Observed by TEM under pH 5.0,the TA-Fe shell would gradually decompose.The released TA as an acidity-activated reductant would reduce Fe³⁺to Fe²⁺,which reacted with overproduced H₂O₂ in TME to generate·OH through Fenton reaction.Heat will speed up this process,thus accelerating the tumor cell apoptosis.The activity of Hela cells treated with the 52.5?g mL^-11 PDA@TA-Fe under 1064 nm laser irradiation decreased significantly,and its viability was only 25.79%;After 15 days of synergistic treatment,the tumor growth was significantly inhibited.In addition,the cell experiments and histologic slices of vital organs analysis showed the theranostic nanoparticles exhibited good biocompatibility.The long-term organ distribution and metabolism experiments indicated the PDA@TA-Fe was mainly metabolized through the hepatobiliary system.Therefore,the PDA@TA-Fe achieved precise imaging-guided efficient synergistic tumor treatment,which would provide foundation in the field of cancer theranostics.