Research On The Preparation Of Anti-cancer Drugs And Anti-tumor Activity Based On Photodynamic Therapy

PDT,as a non-invasive therapeutic approach,has recently attracted widespread interest for cancer treatment.PDT involves the administration of a tumor-localizing PSs followed by local illumination of the tumor with light of a specific wavelength,to activate the PS molecules.The excited PSs then transfer their energy to O,thus generating cytotoxic reactive oxygen species,such as 1O2 that can oxidize key cellular macromolecules leading to tumor cell ablation.However,up to now,most PSs have been activated by visible light.As a consequence,the shallow penetration depth of incident light has limited their otherwise wide applications.Lanthanide doped UCNPs can absorb NIR photons and emit higher energy photons.In this work,we used UCNPs to improve tissue penetration,and designed nanoparticle drug delivery systems,which can effectively improve the PDT activity to cancer cells in vitro.And we also designed a nanometer system which can be used in nuclear magnetic resonance imaging(MRI)and anticancer.Details are as follows:(1)Near-infrared light triggered photodynamic therapy,based on upconversion nanoparticles,has attracted great attention because of high tissue penetration and low photodamage to living organisms.However,most UCNP cannot stable dispersed in aqueous solution and cannot carry photosensitive drug directly.Besides,UCNP mediated PDT is fluorescence resonance energy transfer(FRET)process from UCNPs to the attached photosensitive drugs.So the drug and UCNP should be stable connected and close enough.In this manuscript,carboxymethyl-β-cyclodextrin(COOH-β-CD)was used to connect UCNP and adamantine modified phthalocyanine(Ad-ZnPc).COOH-β-CD can provide good water solubility for the system and close linking between UCNP and Ad-ZnPc.Most importantly,the system has strong NIR light triggered PDT activity to cancer cells in vitro.(2)Carboxyl group modifeid zinc phthalocyanines were classic and widely used photosensitizers(PSs)in upconversion nanoparticles(UCNPs)mediated photodynamic therapy(PDT)for tumor treatment.But carboxyl group modifeid zinc phthalocyanines tend to aggregate both in water and physiological condition,which could sharply decrease its PDT activity.In this manuscript,three zinc(II)phthalocyanine,substituted with 4(ZnPc-(COOH)4),8(ZnPc-(COOH)8)and 16(ZnPc-(COOH)16)COOH groups,were synthesized.Comparison results indicated that ZnPc-(COON)16 existed in monomer form in physiological condition.Besides,ZnPc-(COOH)16 showed superior singlet oxygen(1O2)generation ability to ZnPc-(COOH)4 and ZnPc-(COOH)8.So,we choose ZnPc-(COOH)16 as PSs to absorb on the surface of UCNP.Then,they were encapsulated by the crosslinked methacrylated hyaluronic acid(m-HA),which provides the active tumor accumulation ability by binding its overexpressing receptors on the surface of cancer cell.The result nanoparticles can be effectively taken up by cancer cells and showed strong near-infrared(NIR)light triggered PDT in vitro.(3)Theranostics combine diagnostics and therapy together.Many of the traditional theranostic nanoplatforms involve complicated preparation steps,which are not general and not always possible.In this manuscript,a facile and robust approach to prepare a theranostic nanoplatform,based on chelation interaction between Gd3+and hypericin photosensitizer,has been developed.The result nanopartilce have multifunction of nuclear magnetic resonance imaging(MRI)and anticancer through heavy atom effect(HAE)improved photodynamic therapy and ATP deprivation mechenisms.