The Magnetic Resonance Imaging Contrast Agent Based On Ionic Covalent Organic Frameworks For Diagnosis Of Triple-negative Breast Cancer And Angiography

Magnetic resonance imaging(MRI)has the advantages of high spatial resolution,no tissue penetration limitation,no radiation,and no trauma,so it is conducive to early diagnosis of diseases.The Gd3+ dissociated from the commolly used contrast agent(gadolinium-based contrast agent)is toxic,so the development of contrast agent with low toxicity and high relaxation rate is the current focus and difficulty.Patients with triple-negative breast cancer(TNBC)have a poor prognosis due to the lack of therapeutic targets and susceptibility to lymph node(LN)metastasis.Therefore,more effective methods must be developed to identify early TNBC tissues and LNs.At the same time,the application potential of new synthetic contrast agents can be further explored.Based on these,our work is divided into the following two parts:(1)A magnetic resonance imaging contrast agent(C A)was constructed based on the Mn(Ⅱ)chelated ionic covalent organic framework(iCOF).Due to the porous structure and hydrophilicity,the Mn-iCOF had a high longitudinal relaxivily(r1)of 8.02 mM-1s-1 at 3.0 T.For the in vivo results,the Mn-iCOF at a dose of 0.02 mmol[Mn]/kg performed a higher ratio of signal to noise(SNR)value and a longer retention time(2 h)than that of 10-fold dose of commercial Gd-DOTA(0.2 mmol[Gd]/kg,0.5 h).Moreover,the Mn-iCOF could provide continuous significant MR contrast for popliteal LNs during 24 h,which was enough for accurate evaluation and dissection of LNs.The outstanding MRI properties of Mn-iCOF in TNBC diagnosis may pave a new way for designing more biocompatible MRI CAs with higher resolution.(2)The interreaction of synthetic Mn-iCOF and BSA was investigated,and it was hopeful that MRI signal could be amplified in vivo(relaxation rate enhancement)for T1-weighted imaging(T1 WI).The non-covalent interaction between Mn-iCOF and BSA was verified by UV-vis absorption spectroscopy,fluorescence spectroscopy,circular dichromatography and etc.In the PBS at pH 7.4,the r1 of Mn-iCOF-BSA(4.5%)was enhanced from 7.86 mM-1s-1 to 36.6 mM-1s-1,laying a good foundation for the application of Mn-iCOF in angiography in vivo.