Near-infrared Activated Functional Nanomaterials For Targeted Tumor Therapy

Cance,also known as malignant tumor,is a principal disease which threat the human health and social development.Mutations in the healthy cells will result in excessive deregulated cell proliferation,which is the main reason for cancer formation.Malignant tumor cells can violate and destroy adjacent tissues and organs.Moreover,cancer cells can detach from the primary tumor tissue,circulate with the blood or lymphatic system s and are able to form metastases.Therefore,it is difficult to cure,and has been a great threat to human health.The researches of cancer treatment have never been paused.Traditional surgical,radiotherapy,chemotherapy and other treatment methods have been widely used in clinical applications,but they are easy to cause relapse,toxic side effects and other problems,which seriously affect the final treatment.Therefore,the targeted therapeutic strategy was put forwardit.However,in the process of the treatment only a small amount of drugs can play a role in tumor treatment.Then it is important to find a treatment that can achieve better targeting effect.In recent years,nano-materials have been widely developed due to the small size effect,surface effect,quantum size effect and other advantages.As research continues,a variety of nano-materials were used in cancer threapy,and produced some new treatments.Among them,the photothermal therapy and photodynamic therapy with the use of near-infrared light only on the tumor site due to less damage to normal tissue has been widespread concern.Photothermal therapy is a new treatment that uses the nano-materials with high photothermal conversion efficiency.Under the irradiation of external light source(usually near infrared light)the light energy transforms into heat to kill cancer cells.Semiconductor copper sulfide nano-materials as an emerging new type of NIR plasmonic colloidal nanoparticles has been widely developed.Photodynamic therapy is a new technology which uses photodynamic effects for disease diagnosis and treatment.Under irradiation,the photosensitizer will absorb the light energy,and transfer to the surrounding oxygen to produce highly active singlet oxygen.The singlet oxygen will oxidize the adjacent biological macromolecules,leading to cell damage and even death for cancer treatmen purpose.In this treatment process,near infrared light is a better choice,and upconversion nanoparticles can absorb near infrared light to emit visble light to activate photosensitizer,so the use of upconversion nano-materials emerges at the moment.However,although the treatment of cancer has been widely developed,the treatment effect is also unsatisfactory.So how to make nano-materials in cancer treatment play better is still a problem needed to be addressed.Based on the copper sulfide nanoparticles and the upconversion nanoparticles,this paper designed and synthesized the near infrared light activated functional nanoparticles,which achieved targeted treatment of cancer and prevented relapse.This paper mainly carried out the following two aspects:1.We designed and synthesized a functional nanoparticle which can target into the nucleus for photothermal therapy.First,we firstsynthesized copper sulfide nanoparticles with small sizeand then wrapped a layer of amino groups modified mesoporous silica on the surface of copper sulfide nanoparticles.For further attachment of various polypeptides and dyes.Finally,the peptide TAT,a nucleus targeted peptide,was anchored to the surface of mesoporous silica by covalent attachment of the amino group and the carboxyl group.When the copper sulfide nanoparticles entered the nuclei and were irradiated under 980 nm laser,they could generate heat through photothermal effect and resulted in high tempareture in the nuclear region,which could directly cause the DNA and protein demage and further led to cell death.980 nm as a near infrared light has a deeper tissue permeability,and less damage to normal tissue.The presence of the TAT polypeptide allows the copper sulfide nanoparticles to enter the nucleus successfully,and make the heat generated by the copper sulfide concentrate in the nucleus to degrade the internal DNA and the protein.Thus,we achieved a faster and better therapeutic strategy.The C(RGDyC)polypeptide can bind to the ?v?3 receptor which was overexpressed on the membrane of the cancer cells.When RGD is covalently linked to the copper sulfide surface,the nanoparticles can target to the tumor cells by intravenous injection.Then the nanoparticles will enter into the tumor cells nucleus and kill cells by heat.With this method cancer cells can be quickly and effectively killed,and the purpose of preventing tumor relapse can come true.2.We designed a upconversion nanoparticle/DNA based nanoparticle which can switch its structure and exposed the target group in mild acid tumor microenvironmentand realized th goals of specific identification,uptake,and treatment without damage to normal cells.Upconversion nanoparticles is first coated with polyacrylic acid(PAA,Mw 1800)and then modified with two different lengths of DNA strands.The longer DNA strand is enriched in the C bases and is modified with the photosensitizer ce6 at its end.And the other shorter DNA strand ends with folate.When the nanoparticles circulate in the blood to reach the tumor site,the long-chain DNAs are folded due to the acidic microenvironment of the tumor site.Then the folate on the short-chain DNA can be exposed to achieve in specific target.At the same time,the Ce6 at the ends of DNA is close to the upconversion nanoparticles due to the fold of DNA,and can be activated by the emit of upconversion nanoparticles via FRET.So the singlet oxygen can be produced under the excitation of near infrared light.Therefore,we can achieve in tumor specific treatment and little side effects.