Synthesis and In Vitro Analysis of Dual-Functionalized Mesoporous Silica Nanoparticles for Targeted Theranosis of ER(+) Breast Cancer

Abstract

Mesoporous silica nanoparticles have been extensively utilized for targeted drug delivery; the drugs are encapsulated in the pores, while the surface can be modified to make the nanoparticles target-specific. The work presented here focuses on the development of multifunctional theranostic mesoporous silica nanoparticles with estrogen receptor-positive [ER(+)] breast cancer as the target. The surface of the nanoparticles was dually functionalized to make the nanoparticles target-specific using an estradiol derivative via a facile click reaction and to attach a ^99mTc complexing agent (DTPA) for SPECT imaging. The size of the spherical nanoparticles was 80–110 nm, and the nanosystem was subjected to various physicochemical analysis techniques. Mesoporous nanoparticles were loaded with tamoxifen, an FDA-approved ER antagonist. Drug release at pH 5.8 was much more rapid than at physiological pH 7.4, a beneficial characteristic for controlled drug delivery at the tumor site. Cellular internalization and competitive binding studies indicated estradiol-mediated preferential uptake by MCF-7 cells. The nanocarrier exhibited good antiproliferative activity towards the ER(+) MCF 7 cells with a 92% decline in cellular viability in 48 h, whereas the cellular viability of the estrogen receptor-negative [ER(−)] MDA-MB-231 cells remained > 60%. Thus, our results suggest a high theranostic potential of MSN-Est for breast cancer management.