Design of Water‐Soluble PEGylated Heptapeptide‐Based Multifunctional Magnetic Nanovesicles for Cancer Targeted MRI Integrated With Fluorescence Imaging

Abstract Integrating fluorescent dyes with magnetic resonance imaging (MRI) agents to extract synergistic imaging details is imperative. A de novo designed PEGylated heptapeptide/aggregation‐induced emission (AIE) dye and MRI probe‐conjugated multimodal contrast agent, PEG‐AIE‐Pra‐Lys(DOTAGd 3+ )‐Lys(DOTAGd 3+ )‐Arg‐Gly‐Asp‐Ser, is synthesized employing the Fmoc‐solid phase peptide synthesis approach on Rink amide AM resin. In the heptapeptide sequence, two preorganized macrocyclic Lys(DOTAGd 3+ ) chelates with a substantial magnetic moment (7.49 BM per Gd 3+ ) are incorporated for MRI and integrated with an AIE probe for fluorescence imaging. PEGylation is achieved through PEG‐N 3 and the alkyne‐bearing N‐terminal amino acid L‐propargylglycine (Pra) via click chemistry, which enhances water solubility and circulation lifetime. The multifunctional PEGylated heptapeptide self‐assembles into magnetic nanovesicles in water, facilitating passive targeting of cancer cells. The C‐terminal RGDS residue enables active targeting of the cancer cell surface overexpressed receptor α V β 3 integrin, facilitating preferential delivery of both magnetic and AIE agents to the cancer site. This multifunctional contrast agent is used for live cancer cell‐targeted fluorescence confocal imaging in combination with MRI and exhibits a decent longitudinal relaxation rate ( r 1 ) of 4.0305 mM −1 s −1 . Water‐soluble, biologically compatible, noncytotoxic, AIE‐tethered, macrocyclic Lys(DOTAGd 3+ ) chelates comprising PEGylated paramagnetic nanovesicles of PEG‐AIE‐Pra‐Lys(DOTAGd 3+ )‐Lys(DOTAGd 3+ )‐Arg‐Gly‐Asp‐Ser serves as an effective multifunctional contrast agent for cancer‐targeted multimodal imaging applications.