Multifunctional Hyaluronic Acid Nanoparticles For Cancer Theranostic

Cancer has become a major problem in the field of human health.Early diagnosis and imaging guided therapy are significant for cancer treatment.Nanomedicine including but not limited to liposomes,inorganic nanoparticles,polymer based micelles have been widely used as multifunctional drug carriers for cancer theranostic.An ideal nanosystem should have the following characteristics(1)it should allow early visualization of tumors,(2)it should efficiently deliver drugs to the tumor sites,(3)it is possible to monitor the distribution of the theranostic agent in vivo,(4)it could provide optimized therapeutic strategy under the guidance of imaging in order to reduce side effects.Nanomaterials with high cancer theranostic effectiveness and clinical translational potential are of high desire.In the second chapter,we introduced a novel nanosystem by coating SWCNTs with indocyanine green(ICG)coupled hyaluronic acid nanoparticle(HANPs)for enhanced PDT/PTT cancer treatment under photoacoustic(PA)imaging guidance.In our system,both ICG and SWCNTs have strong near infrared(NIR)absorption and high photothermal conversion efficiency,and are widely used as PA and photothermal agents.HA could actively target to cancer cells overexpressed with CD44,and thus greatly improve the tumor accumulation of the nanosystem.We intravenously(IV)injected IHANPT into xx mice and monitored their tumor accumulation via PA imaging.A NIR laser(808 nm,0.8 W/cm2)was applied to irradiate the tumor area for photothermal therapy.We found that under the guidance of PA imaging,the IHANPT-mediated phototherapy could efficiently ablate the tumor without any tumor recurrence.Photodynamic therapy is another well-known therapeutic strategy.Upon the laser irradiation,the photosensitizer produce reactive oxygen species(ROS)which could kill the tumor cells.The therapeutic efficiency is highly related with the oxygen level.In order to improve the hypoxia state of the tumor microenvironment and thus,improve the photodynamic therapy effect,we designed an oxygen-generating PDT nanocomplex by encapsulating a manganese dioxide nanoparticle(MnO2 NP)into an ICG modified HANPs.The tumor accumulation of the ICG-HANP/MnO2(IHM)nanocomplex was monitored by fluorescent imaging and photoacoustic imaging after intravenous administration into the SCC7 tumor-bearing mouse model.In addition,due to the high reactivity of MnO2 NP to H2O2,the oxygen content in the tumor is elevated to 2.25 ± 0.07 times compared to that without IHM treatment as ultrasound imaging confirmed.After laser irradiation,significant tumor growth inhibition was observed in the IHM-treated group compared to the ICG-HANP-treated group.Further details can be found in the third chapter.In summary,this thesis described two HA based multifunctional nanomaterials for theranostic application.We believe that our design will benefit the cancer theranostic and have clinical translational potential.