Magnetic Liposomal Particles for Magnetic Imaging, Sensing, and the pH‐Sensitive Delivery of Therapeutics

therapeutic agents and deliver these agents to the desired location after specifi c targeting. MNPs can accelerate the spin–spin relaxation of adjacent water molecules, resulting in the faster decay of 1 H NMR signals. The size or chemical composition of MNPs is optimized to increase the transverse relaxivity ( r 2 ), because high r 2 values are desirable as they can improve the magnetic detection or imaging sensitivity in magnetic resonance-based applications. The r 2 value is proportional to the size ( d ) and saturated magnetism ( M s , r 2 ∝ d 2 ⋅ M s 2 ) of MNPs. [ 6 ] The silica shell with amorphous structure coating is expected to improve the safety of the metal oxide particles, but the shell decreases the r 2 value because it decreases the number of water molecules around the magnetic fi eld from the MNP core. In this study, to overcome safety problems and the decreasing r 2 , mesoporous silica ( m SiO 2 ) material was utilized to form a shell around the MNP. The shell possesses a suffi cient number of water molecules inside the pores near the core particles to minimize the decrease in magnetic relaxivity for magnetic applications. [ 7 ] In terms of therapeutics, the mesoporous shell structure can provide suffi cient space for the incorporation of therapeutic agents and the controlled release by adjusting the pH. Generally, the particle surface should be fabricated with hydrophilic moiety as is used for polyethylene glycols (PEGs). This is because an amorphous or mesoporous silica shellcoated MNP does not exhibit long-term solution stability under aqueous solutions, particularly in neutral buffer solutions. [ 8 ] A liposomal formulation with biocompatible phospholipid chemicals was introduced to the magnetic core–shell nanoparticle after encapsulation of the chemical drugs and the therapeutic genes (Figure S1, Supporting Information, MagLipo). [ 9 ] Additionally, for cancer targeting, a cancer specifi c antibody was anchored onto the thiol reactive (maleimide chemical functional group) MagLipo particle surface based on simple bio-conjugation chemistry (see the Experimental Section). [ 10 ] Briefl y, a 16 nm (diameter) iron oxide nanoparticle with a regular size distribution was synthesized using the seedgrowing method. [ 11 ] The MNP was characterized as having a typical ferrite spinel structure, and powder X-ray diffraction and vibrating sample magnetometry revealed that the MNP had a high M s (95 emu per g[Fe]) with superparamagnetism ( Figure 1 A and Figure S2, Supporting Information). To determine the magnetic relaxivity of MNP, the particle was dispersed in H 2 O after being treated with hexadecyltrimethylammonium bromide (CTAB) chemicals and the bare 16 nm MNP was found to have r 2 = 286 m M −1 S −1 by time domain-nuclear magnetic resonance (NMR, Minispec mq20, 0.47 T, Bruker, Billerica, MA, Y. -S. Kwon, H. -S. Cho, Prof. T. -J. Yoon College of Pharmacy Ajou University 206, Worldcup-ro, Yeongtong-gu , Suwon , Gyeonggi-do 16499 , South Korea E-mail: tjyoon@ajou.ac. kr Prof. S. J. Jang, Prof. H. S. Shin College of Medicine and CHA University Bundang CHA Hospital Seongnam 463-712 , South Korea E-mail: shin029@cha.ac. kr Dr. Y. I. Yoon, Prof. H. J. Lee College of Medicine and Seoul National University Bundang Hospital Seongnam 463-707 , South Korea Prof. Y. -S. Cho Department of Internal Medicine Seoul St. Mary’s Hospital College of Medicine, The Catholic University of Korea Seoul 06591 , South Korea E-mail: yscho@catholic.ac. kr Prof. T. -J. Yoon Institute of Pharmaceutical Science and Technology Ajou Universtiy 206 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do 16499 , South Korea