The Application Of Pyropheophorbide A(PPa) Nanomaterials In Cancer Theranostics

In nature,the chlorophyll existed widely in the cells of plant could convert the absorbed light into nutrients for its own growth.Additionally,chlorophyll and its derivatives possess fluorescence characteristics and photodynamic therapy capability.Therefore,researchers have conducted a series of studies,hoping to apply the unique optical properties of chlorophyll in biomedical applications,especially cancer theranostics.However,the low water-solubility of chlorophyll and its derivatives limits their application in biomedicine.In recent years,with the continuous development and innovation of nanotechnology,the biocompatibility and bioavailability of many kinds of drugs have been significantly improved after nano-scalization,further improving the theranositc eficiency of cancer.Objective:The water-solubility and biocompatibility of Pyropheophorbide a(PPa),a chlorophyll derivative,could be improved through drug nanoscalization,achieving better diagnosis and treatment of tumors.The most conventional nano-drug delivery system Liposome was selected to load PPa,obtaining Liposome/PPa nanoparticles,which were used for localization imaging and photodynamic therapy of breast cancer.In order to further increase the PPa loading efficiency,the surfactant Pluronic F127 was mixed with PPa for self-assemble formulation of nano-micelle particles(F127-ppa),which were used to detect early malignant tumors.Methods and results:1.PPa was extracted from silkworm sand by organic solvent.Liposome with PPa loading exhibits excellent biocompatibility and stability.Radionuclides and fluorescent dyes could label stably Liposome/PPa nanoparticles,and further study their distribution at the cellular and animal levels2.Liposome/PPa itself had no acute toxicity.Under the irradiation of 690-nm laser,the generated singlet oxygen could destroy the lysosomal membrane and then induce the cell apoptosis.From the tri-modal imaging including photoacoustic imaging,fluorescence imaging and single-photon emission computed tomography(SPECT),we found that Liposome/PPa showed long-term blood circulaiton and high tumor accumulation,accurately locating the tumor.Under 690nm laser irradiation,Liposome/PPa could produce singlet oxygen to eliminate tumor and inhibit tumor regeneration and metastasis.3.Using the method of peeling the frozen micelles with surfactants,Pluronic F127 and hydrophobic PPa were self-assemble formulation of nano-micelle particles with a hydrophilic shell and a hydrophobic core.After ultrafiltration at low temperature,the loose excipientsa was removed,leaving a highly concentrated frozen micelles abd further improving the encapsulation efficiency of PPa.The maximum absorption peak wavelength of F127-PPa was at 710 nm,which was 40 nm red shifted from the maximum absorption wavelength of PPa alone.4.F127-PPa could enter the cancer cells through endocytosis,exhibiting good light stability and strong near-infrared fluorescence properties.From in vivo fluorescence imaging,we found that F127-PPa could trace tumors with a mass of 5mg to 800mg on the body surface,as well as the early metastatic tumors in the lungs.Conclusion:In this paper,two different strategies were adopted to construct nanoparticles with PPa loading,significantly improving the water-solubility of PPa,which could realize the excellent cancer theranostics and provide the valuable information for the planning of treatment.It is hoped that our work further promote the the clinical application of PPa in the future,and provide a new idea and strategy for the development of green and safe multifunctional nano-agents for the diagnosis and treatment of tumors.