Surface engineering of hollow gold nanoparticle with mesenchymal stem cell membrane and MUC-1 aptamer for targeted theranostic application against metastatic breast cancer

Mesenchymal stem cell membrane (MSCM)-coated biomimetic doxorubicin-loaded hollow gold nanoparticles were fabricated and decorated with MUC1 aptamer in order to provide smart theranostic platform. The prepared targeted nanoscale biomimetic platform was extensively characterized and evaluated in terms of selective de-livery of DOX and CT-scan imaging.The fabricated system illustrated spherical morphology with 118 nm in diameter. Doxorubicin was loaded into the hollow gold nanoparticles through physical absorption technique with encapsulation efficiency and loading content of 77%+/- 10 and 31%+/- 4, respectively. The in vitro release profile demonstrated that the designed plat-form could respond to acidic environment, pH 5.5 and release 50% of the encapsulated doxorubicin during 48 h, while 14% of the encapsulated doxorubicin was released in physiological condition, pH 7.4 up to 48 h. The in vitro cytotoxicity experiments on 4T1 as MUC1 positive cell line illustrated that the targeted formulation could significantly increase mortality at 0.468 and 0.23 mu g/ml of equivalent DOX concentration compared to non -targeted formulation while this cytotoxicity was not observed in CHO as MUC1 negative cell line. Further-more, in vivo experiments showed high tumor accumulation of the targeted formulation even 24 h after intra-venous injection which induced effective tumor growth suppression against 4T1 tumor bearing mice. On the other hand, existence of hollow gold in this platform provided CT scan imaging capability of the tumor tissue in 4T1 tumor bearing mice up to 24 h post-administration. The obtained results indicated that the designed paradigm are promising and safe theranostic system for fighting against metastatic breast cancer.

Automated summary

We fabricated and decorated MSCM-coated biomimetic doxorubicin-loaded hollow gold nanoparticles with MUC1 aptamer to create a smart theranostic platform. The platform exhibited a spherical morphology with a diameter of 118 nm. In vitro release experiments showed that the platform could respond to acidic environments, releasing 50% of encapsulated doxorubicin in 48 hours, while only 14% was released in physiological conditions. The targeted formulation demonstrated increased cytotoxicity against MUC1 positive cell line and effective tumor growth suppression in vivo.