Folic Acid Conjugated Graphene Oxide Graviola Nanoparticle For Sono-Photodynamic Leukemia Treatment:Up-To-Date Cancer Treatment Modality

Background:There is no doubt that one of the largest researcher dilemmas is cancer.Traditional therapeutic options such as chemotherapy,radiation,surgical and combinational treatment are widely accepted to cure or eradicate tumors.Despite the fact that chemotherapy being a very potent weapon for cancer treatment,it is overwhelmingly associated with severe side effects.There is consistently a probability of recurrence,and these cancers can evolve resistance to chemotherapy and radiation treatments.Therefore,seeking new therapeutic options of treatment is necessary to treat tumors accurately and prevent cancer metastasis.Leukemia,as one type of cancer is,occurred due to bone marrow clonal disorder that originates during hematopoiesis and is characterized by the poorly white blood differentiated cells’ unregulated proliferation.Based on the type and proliferation degree of affected cells,the disease is classified as myeloid or lymphoid and acute or chronic,respectively.The most prevalent type in adults and among pediatric patients is acute,myeloid,and lymphocytic leukemia;(AML,ALL),respectively,with incidence and mortality of(4.2,1.7 cases)and(2.8,0.4 cases),respectively,annually per 100,000 persons.Myeloproliferative disorder accounting for 15-20%of adults newly leukemia diagnosed cases is Chronic myeloid leukemia(CML),with incidence and mortality of 1.8 and 0.4 cases,respectively,annually per 100,000 persons.Photodynamic therapy(PDT)treatment method has been established to treat different kinds of cancers.PDT involves a photo-sensitive drug intake and subsequently illuminating with light corresponding to the sensitizer absorbance wavelength of the target area.Factors that govern PDT cancer therapy;are the photosensitizing agent localization in cancerous tissue and an appropriate light dose delivered to that tissue.Sonodynamic therapy(SDT)treatment method has evolved from PDT to overcome light short infiltration deepness.SDT involves a sono-sensitive drug intake,and the target area is subsequently exposed to ultrasound.Using of SDT enabled penetration of up to several tens of centimeters of tissue.Consequently.SDT put an end to PDT obstacles and major limitations.Sono-photobiomodulation therapy(SPBMT)is a treatment method that includes the intake of photo-and sono-sensitive agents.PDT has been conducted separately from SDT for years with variable success for cancer treatment.PDT has been directed for superficial cancer,while in the combination with SDT,it showed effectiveness against leukemia,deep-seated,and metastatic tumors when spread to lung,liver,and bone in particular.Annona muricata(Graviola)is a small erect evergreen,tropical fruit tree,growing 5-6m in height,belonging to the family Annonaceae.Traditionally Graviola is employed in cancer treatment.Through altering cell metabolism,the Graviola extract manifested promising selective tumorigenic inhibitory effects in vitro and in vivo.Objective:This work was directed at evaluating of the efficacy of using activated Graviola nano-composite for leukemia targeted therapy.This work was conducted in vitro(two leukemia cell lines),and in vivo(90 leukemia induced mice).Laser and ultrasound were applied as an energy source.Material and methods:In this work,the biological effectiveness of using activated Graviola nano-composite for leukemia targeted therapy was investigated through biophysical[Shape,size,absorbance,and photoluminescence were determined using SEM,TEM,X-ray diffraction,and energy dispersive(XRD,EDX scan),UV/Visible scan spectrometer,PL scan spectrometer,and Fourier transform infrared spectroscopy(FTIR scan)],biochemical[SRB cell viability and Cytotoxicity IC50,antioxidant enzyme activities;superoxide dismutase,catalase,glutathione reductase,glutathione-s-transferase,total antioxidant capacity(SOD,CAT,GR,GST,and TAC),malondialdehyde MDA,liver function tests;alanine aminotransferase ALT and aspartate aminotransferase AST,kidney function tests;creatinine and urea,p53,Bax,Caspase(9,3),NFkB,TNFalpha,VEGF,Bcl-2 qRT-PCR relative gene expressions],and hematological[complete blood count CBC]analysis.Results:The results revealed that Graviola nano-composite is a potential promising photosono sensitizer for cancer treatment and plays a critical role both in vitro and in vivo in induction of cancer cell death.Conclusion:Our results revealed that activated Graviola nano-composite could be applied as a natural nano-sensitizer for sono-photodynamic therapy(SPDT)cancer targeting.