Study On The Effect Of Platelet Membrane Camouflaged Nanosystem In The Diagnosis And Treatment Of Breast Cancer

Purpose: The prognosis of breast cancer patients with lung metastasis is poor,meanwhile,the application of surgery and neoadjuvant therapy currently cannot avoid postoperative recurrence and metastasis.Moreover,there is a lack of effective diagnostic and therapeutic methods for breast cancer metastasis,and it is often difficult to reverse the damage once metastasis is detected.Finding new diagnostic and therapeutic methods for anti-breast cancer metastasis is still an important problem that urgently needs to be solved in clinical practice.Based on this,this study constructed a platelet membrane camouflage nanosystem E-PLTm@FPD to explore the mechanism of its anti-breast cancer and metastasis,and verify its effect on the auxiliary diagnosis of breast cancer.Methods: This novel anti-breast cancer metastasis nanosystem is named E-PLTm@FPD,which mainly consists of two parts:(1)Fe WOx@Pt nanoparticle(FP)as the core,loaded with small molecule targeted drug dasatinib(DAS);(2)breast cancer targeting peptide E5 inserted into platelet membrane(platelet membrane,PLTm)to form the shell part(E-PLTm).Further verification of the effect of anti-breast cancer and metastasis of the constructed nanosystem E-PLTm@FPD was conducted through in vitro and in vivo experiments,and its computed tomography(CT)and magnetic resonance imaging(MRI)characteristics were also detected.Results:(1)With PLTm camouflage,E-PLTm@FPD could evade macrophage phagocytosis and targeted breast tumor sites with high expression of C-X-C chemokine receptor 4(CXCR4).(2)E-PLTm@FPD had good photodynamic therapy(PDT)and photothermal therapy(PTT)effects,efficiently producing reactive oxygen species,singlet oxygen species,and inducing thermal damage to kill tumor cells.(3)EPLTm@FPD inhibited tumor cell migration and invasion by suppressing the Src/ Phosphoinositide 3-kinase(PI3K)/ Matrix metalloproteinase-9(MMP9)pathway.(4)E-PLTm@FPD could act on the pre-metastatic niche(PMN)before lung metastasis,reshaped the lung vasculature system,reduced the level of Hypoxia-inducible factor 1α(HIF-1α),inhibited lysoxygenase(LOX)/ lysoxygenase-like 2(LOXL2)expression,and recruited bone marrow-derived cells(BMDCs),thus normalizing the PMN and preventing breast cancer lung metastasis.(5)E-PLTm@FPD had excellent CT and MRI imaging functions,making it possible to monitor tumor progression.Conclusion: E-PLTm@FPD,as a safe and efficient diagnostic and therapeutic tool,could inhibit breast cancer progression and metastasis through multiple pathways,providing a new strategy for the treatment of breast cancer.