Design of Water-Soluble PEGylated Heptapeptide-Based Multifunctional Magnetic Nanovesicles for Cancer Targeted MRI...

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(DOTAGd³⁺)-Lys(DOTAGd³⁺)-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(DOTAGd³⁺) chelates with a substantial magnetic moment (7.49 BM per Gd³⁺) are incorporated for MRI and integrated with an AIE probe for fluorescence imaging. PEGylation is achieved through PEG-N₃ 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_Vβ₃ 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 (r₁) of 4.0305 mM^-1 s^-1. Water-soluble, biologically compatible, noncytotoxic, AIE-tethered, macrocyclic Lys(DOTAGd³⁺) chelates comprising PEGylated paramagnetic nanovesicles of PEG-AIE-Pra-Lys(DOTAGd³⁺)-Lys(DOTAGd³⁺)-Arg-Gly-Asp-Ser serves as an effective multifunctional contrast agent for cancer-targeted multimodal imaging applications.