Smart Thermal-Responsive Nanocarriers For Cancer Therapy

In cancer treatment,the targeted delivery and controlled release characteristics of the nanocarriers could effectively enhanee therapy effieacy and alleviate side effeect.Smart stimulus-responsive nanocarrier could specifically accumulate at tumor sites and controllably release in target cells when it is triggered by external signals,such as chemical signals,temperature,pH and so ort,which makes it gain considerable attentions for cancer therapy in recent years.In this paper,we choose the abnormal expressive cell surface receptors and microRNA as research object,gold nanomaterials and temperature-responsive polymer as basic components of nanocarriers,to realize the tairgeted delivery,controlled release of drug and enhance therapy efficacy.1.Smart thermal-activated nanocarriers for the manipulation of cellular uptake and photothermal therapy on commandWe have developed smart nanocarriers consisting of hollow gold nanoshells as the photothermal controller,PEG-tailed thermo-sensitive polymers as the vessel,and AS1411 aptamer as the navigator,to realize NIR?guided cellular uptake and photothermal therapy.Different from conventional nanocarriers,in our design,the switchable surface efficiently eliminated the nonspecific interaction of PEG/apt-HGNSs with normal cells in the PEG state,while enhanced the specific uptake by tumor cells in the aptamer state controlled by NIR irradiation,resulting in improved therapeutic efficacy towards tumor cells and minute side effects to normal cells.To further test the controllability of nanocarriers in the photothermal therapy,three tumor cells with nucleolin overexpressed and two normal cells with nucleolin no-expressed were chosen.By spatially and temporally modulating the NIR irradiation,the exposure of AS1411 aptamer could specifically recognize the nucleolin and enhance cellular uptake and the photothermal therapy efficacy could be finely controlled on command.The viability of three tumor cells were lower than 50%while minute side effects to the normal cells.With the development of nanotechnology,the idea of manipulating surface composition of nanoparticles has opened a novel way to design smart nanocarriers for target delivery and controlled release of drugs in tumor cells.2.Smart thermal-activated nanocarriers for microRNAIATP-Controlled release of siRNA and Dox.We developed the smart nanocarriers consisting of gold nanorods as photothermal controllers,thermo-sensitive polymers as navigators,and Y-motifs as DNA nanorobots to realize the targeted delivery and controlled release of siRNA and Dox.The PEG corona of the smart nanocarriers made the D/R/SNCs stealthy during blood circulation,protected the siRNA from nuclease degradation,eliminated the nonspecific uptake by normal organs and facilitated the passive accumulation at tumor sites,where specific cellular uptake were achieved under the guidance of NIR laser.The release of siRNA and Dox in the nanocarrier was achieved via microRNA as trigger and ATP as fuel through toehold-mediated strand displacement,thus synergetic inhibition to tumor growth and minute side effect to normal tissues.Under the NIR irradiation,the surface composition was altered by heating the nanocarriers through photothermal conversion,concomitant with the shrinkage of P39PEG and exposure of the RGD shell,which specifically recognized the integrin overexpressed in most tumor cells.The release of coupling siRNA and intercalating Dox could activate the apoptosis-induced cell death,enhance the therapy efficacy.With the development of DNA nanotechnology,particularly in aptamer screening and DNA origami,multifunctional DNA nanostructures responsive to exclusive intracellular stimuli can be designed,providing smarter nanodevices that work like viruses for the personalized treatment of human disease with gene and drugs.