| Nowadays,cancer is the leading cause of human death.The existing tumor treatment methods including surgery,chemotherapy,and radiotherapy are difficult to meet the urgently needs of cancer paitients.It is because surgical treatment is difficult to deal with metastatic tumors,and radiotherapy and chemotherapy lead to the serious toxic side effects and tumor cell resistance.Therefore,finding effective strategies to treat cancer has become an urgent need in clinical cancer treatment.With advanced nanotechnology,nanomedicine has shown unique advantages and good application prospects in many fields of cancer treatment.In our doctoral thesis,in order to effectively inhibit cancer metastasis in clinical tumor surgery,we have designed a variety of nanomaterial-based imaging-guided photothermal strategies to clean tumor sentinel lymph nodes.Compared with traditional surgical resection,our strategy can effectively prevent tumor metastasis and recurrence.In addition,an activve targeting agent was prepared by growing polypyrrole onto 131I loaded transferrin for combined photothermal theray with radiotherapy.Furthermore,we have designed a strategy to increase the tumor-specific uptake of the second wave of therapeutic nanoparticles,which improve tumor vascular permeability by pretreated tumor using 131I loaded liposome.Our doctoral thesis provides new thinking for cancer therapy-related nanomedicine.Chapter 2:SWCNTs-PEG work as the theranostic agent for imaging and photothermal ablation of metastatic sentinel lymph nodes(SLNs)in an animal tumor model.By using NIR-Ⅱ fluorescent imaging,SWNTs were tracked after i.t.injection.SWNTs moved from injected primary tumor to the nearby sentinel lymph node.Due to the effective retention of the SWNTs in the sentinel lymph node,photothermal therapy(PTT)primary tumor and sentinel lymph node offered greatly improved animal survival and remarkably inhibited pulmonary metastasis.Chapter 3:With an external magnetic field(MF)focused on the SLN sites,PEG-functionalized gold shelled iron oxide nanoclusters could effectively migrate from primary tumors to those lymph nodes and get accumulated there,as monitored by in vivo:magnetic resonance(MR)imaging.Such enhanced SLN uptake of our magnetic theranostic nanoparticles by magnetic targeting allows us to use a rather low dose of IONC@Au-PEG(ca.0.05 mg per mice)and a mild NIR power density(0.5 W cm-2)for photothermal ablation of metastatic tumor cells located inside SLNs.Chapter 4:Transferrin is pre-labeled with iodine-131(131I)and then utilized as the stabilizer in the fabrication of polypyrrole(PPy)nanoparticles.The obtained transferrincapped PPy@Tf-131I nanoparticles could be used for tumor-targeted radioisotope therapy(RIT)and PTT,by employing beta-emission from 131I and the intrinsic high near-infrared(NIR)absorbance of PPy,respectively.Owing to the transferrin-mediated tumor targeting,PPy@Tf-131I nanoparticles exhibit obviously enhanced in vitro cancer cell binding and in vivo tumor accumulation compared to its non-targeting counterpart.The combined RIT and PTT based on PPy@Tf-131I nanoparticles are then conducted,achieving a distinct synergistic therapeutic effect.Chapter 5:We propose a strategy using internal radioisotope therapy delivered by liposomal nanoparticles to improve the tumor vasculature permeability,so as to increase the tumor specific uptake of the second-wave therapeutic nanoparticles for enhanced cancer therapies.Therapeutic radioisotope iodine-131 is labeled onto albumin-encapsulated liposomes with greatly improved radiolabeling stability compared to 131I labeled albumin.The obtained 3 I-liposome with long blood half-life could accumulate in the tumor and damage tumor blood endothelial cells to improve the tumor vascular permeability.As the result,the tumor retention of the second wave of liposomal nanoparticles could be greatly increased owing to the RIT-enhanced EPR effect.In three separated experiments,we then demonstrate that such strategy could be utilized for photothermal therapy,hypoxia-activated chemotherapy(HCT)and checkpoint blockade immunotherapy,all of which could be enhanced by RIT with excellent in vivo synergistic therapeutic outcomes.In summary,we developed various multi-functional nanomaterials to deal with various problems in cancer treatment.We built tumor sentinel lymph node metastasis model and carefully designed two strategies based on our developed multi-functional nanomaterials to inhibit tumor metastases.And transferrin-mediated active tumor targeting nanoparticles were developed to treat U87MG tumor by photothermal therappy combined with radiotherapy.Using internal radioisotope therapy delivered by liposomal nanoparticles,tumor vasculature permeability could be improved,leading to increasing tumor capture of nano-drugs.This stratege could work on various nanoparticle-based therapy. |
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