Developing Nanomedicine Approaches:Design,Synthesis,and Evaluation Of New Nanomaterials For Cancer Therapy

Optically active nanomaterials have shown great promise interesting as a nanomedicine platform for cancer phototherapy and imaging.However,the limited treatment efficacy and possible side effects arising from monotherapy altered the trend in current research to combination therapy for enhancing anticancer efficiency.Very recently,precision therapy combines the advantages of imaging-guided multimodal synergistic treatment,which can provide a higher therapeutic index and more rigorous diagnosis than solitary imaging or ordinary therapy has shown highly desirable interesting for cancer treatment.Motivated by the above requirements,in this thesis,we strategically designed and fabricated innovative multifunctional phototherapeutic nanoagents to overcome the limitations of a single mode therapy and pursue higher therapeutic efficiency via synergistic effects of cancer diagnosis and therapy.This thesis includes three parts which are summarized in the following lines:In the first part,an efficient phototherapeutic nanoagent for synergistic photothermal/photodynamic therapy?PTT/PDT?effect has been synthesized.Herein,we have successfully functionalized the FDA-approved prussian blue?PB?with the oxygen-deficient molybdenum oxide nanoparticles?MoO₃-x NPs?by a facile one-pot size/morphology-controlled process.The as-prepared PB-MoO₃-x,nanocomposites?NCs?with a uniform particle size of?90 nm and high water dispersibility exhibited strong optical absorption in the first biological window,which is induced by plasmon resonance in an oxygen-deficient MoO₃-x semiconductor.More importantly,PB-MoO₃-x NCs not only exhibited a high photothermal conversion efficiency of?63.7%and photostability but also offered a further approach for the generation of reactive oxygen species?ROS?upon singular near-infrared?NIR?light irradiation which significantly improved the therapeutic efficiency of the PB agent.Furthermore,PB-MoO₃-x NCs showed a negligible cytotoxic effect in the dark,but an excellent therapeutic effect toward two triple-negative breast cancer?TNBC?cell lines at a low concentration?20 mg/mL?of NCs and a moderate NIR laser power density.Additionally,efficient tumor ablation and metastasis inhibition in a 4T1 TNBC mouse tumor model can also be realized by synergistic PTT/PDT under a single continuous NIR wave laser.Taken together,this study may serve as a platform to develop a single nanosystem for accelerating multifunctional cancer therapeutics.In the second part,a multifunctional theranostic nanoplatform has been modified as an oxygen generator nanosystem for imaging-guided single-NIR-laser triggered synergistic PDT/PTT treatment.Herein,we basically constructed an effective phototherapeutic nanoplatform based on chlorin?e6?functionalized polydopamine coated prussian blue/manganese dioxide nanocomposites?PB-MnO₂@PDA@Ce6 NCs?.Interestingly,the PDA coating PB-MnO₂ NPs not only offered an effective delivery system for Ce6 but also provided a strong optical enhancement in the NIR range and achieved high tumor ablation efficacy.More importantly,the as-prepared PB-MnO₂@PDA@Ce6 NCs exhibited effective O₂ generation,superior ROS,and outstanding PTT ability to further dual enhancements of PTT and PDT treatments.Resultantly,both in vitro and in vivo investigations guided by MRI imaging on liver cancer cells revealed the complete cell/tumor eradication under single 660 um laser irradiation,implying the simultaneous synergistic PDT/PTT effects induced by PB-MnO₂@PDA@Ce6 NCs,which are much higher than individual treatment.Taken together,our nanotherapeutic agent offers an excellent therapeutic performance,which may act as a platform to discover safer and clinically translatable methods for enhancing cancer therapeutics.In the last and third part,Fe₂O₃@PEDOT core-shell nanoparticles have been prepared for effective photothermal/gene synergistic therapy of breast cancer.Herein,we have successfully developed unique core-shell nanoagents for a combination of photothermal therapy?PTT?and gene therapy?GT?of cancer cells,poly?3,4-ethylenedioxythiophene?PEDOT shells coating on hematite??-Fe₂O₃?nanoparticles are prepared by one-pot in situ oxidative polymerization method.The obtained Fe₂O₃@PEDOT core-shell nanoparticles exhibit a strong optical absorbing enhancement in the Vis-NIR region as compared with pristine a-Fe₂O₃ NPs as well as a positive surface charge.More importantly,the good biocompatible of Fe₂O₃@PEDOT core-shell NPs not only display an efficient photothermal conversion efficacy and photostability for PTT but also act as an effective carrier to deliver small interfering RNA?siRNA?to breast cancer cells.As a result,the obtained Fe₂O₃@PEDOT@siRNA nanocomplexes exhibit enhanced therapy effect on two types of breast cancer cells under NIR laser irradiation,as compared with an individual PTT or GT treatment,which is induced by synergistic GT/PTT therapy.This is the first example of the use of using Fe₂O₃@PEDOT core-shell NPs for delivery of siRNA to achieve highly effective photothermal/gene combination therapy.Our work provides a potent allowing antitumor approach to continuing the administration of inorganic materials@conjugated polymer core-shell nanosystems in the biomedical field.