Phototheranostic Nanoagents for Imaging-Guided Treatment of Oral Cancer

Phototherapy showed almost a lack of drug resistance and,depending on the therapeutic effects of non-invasive light-stimulating photosensors.The side effects of phototherapy were greatly reduced compared to their traditional equivalents.Phototheranostic nanoagents had new properties in drug delivery,biocompatibility,targeting and response,in which traditional phototheranostic drugs can not possess.Recently,a large number of relevant studies have demonstrated that photodynamic therapy(PDT)in combination with other agents and image-guided multifunctional photothermal therapy(PTT)were well suited for the treatment of oral cancer.Through the design of the nanoagents,researchers have discovered various applications for phototherapy,such as targeted release of co-packaged drugs,multifunctional imaging for diagnosis and treatment combination,accurate targeting caused by nanocarriers,and synergistic chemotherapy with phototherapy.In this paper,we first reviewed the research related to phototheranostic nanoagents for image-guided treatment of oral cancer.We tried to introduce the design concept and the treatment effect by three parts of components of phototheranostic nanoagents,categories of phototheranostic nanoagents and application of phototheranostic nanoagents.It also provided a reference for nanomaterial development and clinical applications in research of oral cancer treatment.

Photoacoustic and magnetic resonance imaging-based gene and photothermal therapy using mesoporous nanoagents

The integration of photothermal therapy(PTT)with gene therapy(GT)in a single nanoscale platform demonstrates great potential in cancer therapy.Porous iron oxide nanoagents(PIONs)are widely used as magnetic nanoagents in the drug delivery field and also serve as a photothermal nanoagent for photothermal therapy.However,the therapeutic efficacy of PIONs-mediated GT has not been studied.The long noncoding RNA(lncRNA)CRYBG3(LNC CRYBG3),a lncRNA induced by heavy ion irradiation in lung cancer cells,has been reported to directly bind to globular actin(G-actin)and cause degradation of cytoskeleton and blocking of cytokinesis,thus indicating its potential for use in GT by simulating the effect of heavy ion irradiation and functioning as an antitumor drug.In the present study,we investigated the possibility of combining PIONs-mediated PTT and LNC CRYBG3-mediated GT to destroy non-small cell lung cancer(NSCLC)cells both in vitro and in vivo.The combination therapy showed a high cancer cell killing efficacy,and the cure rate was better than that achieved using PTT or GT alone.Moreover,as a type of magnetic nanoagent,PIONs can be used for magnetic resonance imaging(MRI)and photoacoustic imaging(PAI)both in vitro and in vivo.These findings indicate that the new combination therapy has high potential for cancer treatment.

Self-Assembled Nanomicelles of Affibody-Drug Conjugate with Excellent Therapeutic Property to Cure Ovary and Breast Cancers

Affibody molecules are small nonimmunoglobulin affinity proteins,which can precisely target to some cancer cells with specific overexpressed molecular signatures.However,the relatively short in vivo half-life of them seriously limited their application in drug targeted delivery for cancer therapy.Here an amphiphilic affibody-drug conjugate is self-assembled into nanomicelles to prolong circulation time for targeted cancer therapy.As an example of the concept,the nanoagent was prepared through molecular self-assembly of the amphiphilic conjugate of Z_(HHR2:342)-Cys with auristatin E derivate,where the affibody used is capable of binding to the human epidermal growth factor receptor 2(HER2).Such a nanodrug not only increased the blood circulation time,but also enhanced the tumor targeting capacity(abundant affibody arms on the nanoagent surface) and the drug accumulation in tumor.As a result,this affibody-based nanoagent showed excellent antitumor activity in vivo to HER2-positive ovary and breast tumor models,which nearly eradicated both small solid tumors(about 100 mm^(3)) and large established tumors(exceed 500 mm^(3)).The relative tumor proliferation inhibition ratio reaches 99.8% for both models.

Nanoplatform-based cellular reactive oxygen species regulation for enhanced oncotherapy and tumor resistance alleviation

The cancer cells realize their proliferation and metastasis activities based on the special redox adaptation to increased reactive oxygen species(ROS)level,which inversely makes them sensitive to external interference with their redox state.In view of this,in recent decades,researchers have made great efforts to construct a series of novel nanoplatform-based ROS-mediated cancer therapies through increasing ROS generation and inhibiting the ROS elimination.Besides,the multidrug resistance and thermoresistance of tumor are closely related to tumor redox state.Recently,numerous works have shown that ROS regulation in cancer cells can intervene in the expression,function and stability of related proteins to achieve reversal of tumor resistance.In this review,the recent researches about ROS-regulating nanoagents on cancer therapy and tumor resistance alleviation have been well summarized.Finally,the challenges and research directions of ROS-regulating nanoagents for future clinical translation are also discussed.

Light-guided tumor diagnosis and therapeutics:From nanoclusters to polyoxometalates

Malignant tumors,with the characteristics of easy metastasis and recurrence,are a serious threat to health of mankind.It is urgent to develop promising clinical cancer targeted agents with combination of rapid diagnosis and efficient therapies.Compared with the conventional photosensitizing agents,the recent advances of nanoagents based on transition metal-oxide clusters possess unique structural and electronic properties,greatly improving cancer survival rate,meanwhile,keeping high contrast imaging.This review provides a brief introduction of metal-oxide clusters,including both nanoclusters to molecular clusters,specifically polyoxometalates(POMs).Subsequently,biocompatibility of metal-oxide clusters is emphasized from aspects of endocytosis,macropinocytosis,and phagocytosis.Through the classification of late and early transition metals oxide clusters,recent outcomes of light-guided nanoagents are represented with their intriguing chemical and optical properties in their diagnosing and photochemotherapy performance.It shed light on the summary of next generation multifunctional cancer targeting agents'developments as well as outlook of materials selection trends and research direction in the future.