Study On Targeting Imaging Of Breast Cancer Based On The Novel Functional Water-soluble Quantum Dots Probe

Breast cancer has been considered as the most commonly diagnosedcancers in female and is one of the highest cancer mortality rates ofmalignant tumor. The high heterogeneity of breast cancers requires amore thorough understanding in the biological characteristics of breastcancer have. The personalized medicine for BC has become the dominantstrategy in clinical practice, which required the understanding of the BCbiological behaviors. As two key emerging molecules for BCclassifications, estrogen receptor (ER), progesterone receptor (PR) havebecome increasingly important in treatment selection, prognosisprediction and disease course monitoring.Semiconductor quantum dots (QDs) have attracted great attentionfor the last two decades，which due to their unique optical and electronicproperties such as bright fluorescence, narrow emission, broad excitation,and high photostability. It has been used for a broad range of biologicalapplications especially early cancer diagnosis. However, the preparedQDs are not water dispersible. In order to employ QDs for biosensing andbiomedical imaging applications, they need to be water-dispersible andbiocompatible with the biological environment. In this paper, the QD-ERand QD-PR probes were synthesis based on the water-soluble QDs forbreast cancer targeting imaging in vitro and in vivo.Hydrophobic octadecylamine-coated QDs were encapsulated withamphiphilic biocompatible centipede-like polymer p(aspartate)-Na- graft-p(ethylene glycol)-dodecylamine (PASP-Na-g-PEG-DDA), andthen conjuncted with ER monoclonal antibodies and PR monoclonalantibodies respectively to synthesis the QD-ER and QD-PR probes. Theprobes showed excellent solubility and stability. The UV-Vis absorptionspectrum and PL intensity of QD-ER probes indicated that theconjugation process did not affect the structure of the QD nanocrystalsand still have the optical and electronic properties of QDs. These resultsprovide the basis for future experiment in vitro and vivo.The novel water-soluble QD-ER and QD-PR probes were used toevaluate the ability to recognize ER and PR in breast cancer cells in vitro.The results demonstrated that the QD-ER and QD-PR probes not only canspecically bind to the target receptor, also can immunofluorescencelabeling both ER and the PR in MCF7（ER positive and PR positive）cells at the same time. Nonspecic binding was observed with mockconjugated QDs in MCF7cells. No binding was seen in MDA-MB-231cells（ER negative and PR negative) too. For the biomedical applications,in vitro cytotoxicity experiment was necessary to study the toxicity of theprobes. The results were showed that the QD-ER or QD-PR probes haveno obvious toxic side effects on living cells. The photostabilitycomparison test of QD-ER probes with traditional organic fluorescentdye-Alexa Fluor488showsed the QD-ER probes was much morestable.This advantage is very important for tumor long-time observationin the future. All the results indicated that, the new kind of probes hadgreat potential in the diagnosis of breast tumor in vitro in future clinicalapplication. It may have a positive impact not only in in vitro but also invivo molecular and cellular imaging in cancer research such as long timeobservation.To demonstrate the capability for in vivo targeting, the QD-ER probes were injected to the mouse through tail vein injections. Theimaging study showed that QD-ER probes were able to target tumor siteafter intravenous injection of the formulation in tumor-bearing mice. Wealso analysis the in vivo cytotoxicity experiments of the important organssuch as heart, lung, kidney, brain and liver. No signs of toxicity wereobserved in the tissues from the animals receiving the probes as comparedto the H&E-stained tissue sections from the animal treated with PBSbuffer solution. All the results above indicated that antibody conjugatedwith QD can be a promising probe was able to target tumor site afterintravenous injection of the formulation in tumor-bearing mice in thetumor markers detection and tumor diagnosis.In summary, the hydrophobic octadecylamine-coated QDsencapsulated with (PASP-Na-g-PEG-DDA), modied with ER and PRmonoclonal antibodies. The QD-ER and QD-PR probes both showedexcellent solubility, stability, and can specically bind to the ER and PR ofbreast cancer cells individually and simultaneously in vitro. The probesalso could be used to target tumor site in tumor-bearing mice. In vitro andin vivo analysis both showed that no obvious cytotoxicity experimentswere observed.According to the analysis above, this new kind of probe has a greatpotential for the breast tumor detection, diagnosis and long-term fateobservation of tumors in future clinical application. We believe thatprobes could lead to great potential in applications such as nanodiagnosisand nanotherapy of early breast cancer in near future.