Photodynamic Cancer Therapy Based On Semiconducting Polymer Dots

Photodynamic therapy(PDT)which undergos abundant studies and extensive explorations,has been successfully applied to clinical cancer therapy.In contrast with conventional cancer treatments,PDT possesses unique advantages including minimally invasive nature,tolerance of repeated doses,fast treatment process,and without additional damage to surrounding tissues.However,most photosensitizers used in PDT are hydrophobic in nature,making them easily form aggregates in aqueous solution,leading to low bioavailability,insufficient ROS yield and unsatisfactory therapeutic effects.Other factors including limited tissue penetration depth,poor tumor selectivity and low absorption coefficients of photosensitizers can also affect the photodynamic effect in practical cancer treatment.Therefore,in order to overcome the above problems associated with molecular photosensitizers,various photosensitizers loaded nanoparticles,such as polymeric nanoparticles,upconversion nanoparticles,gold nanoparticles,mesoporous silica nanoparticles and quantum dots have been explored sequentially.Semiconducting polymer dots(Pdots)with remarkable optical properties,thus become the research focus in biomedical field.For PDT applications,Pdots can be used as a carrier to load hydrophobic photosensitizer to overcome the problem of photosensitizer solubility.More importantly,Pdots serve as light harvesting matrix and transfer energy to the photosensitizer for amplified reactive oxygen species(ROS)generation.Despite the progresses,the absorptions of most currently available Pdot species are in the blue region that has a limited tissue penetration depth.Next,small molecular photosensitizers loaded into Pdots through physically doping,can easily lead to photosensitizers leaching.In addition,the slow uptake of carboxyl Pdots in cancer cells,needs longer incubation time to play good therapeutic effect.Thus,to overcome the problems above,we focused on PDT,carried out a large number of experimental studies,and obtained the following innovative research results:1.We synthesized a photocrosslinkable semiconducting polymer with the absorption band in green region,and prepared photosensitizer doped Pdots,whose side chains could form a polymeric network via photocrosslinking reaction,stably retaining the photosensitizer molecules inside the Pdots.In our studies,we prepared photosensitizer Chlorin e6(Ce6)doped Pdots(Ce6-doped Pdots)through reprecipitation method,they possessed with good optical properties and high generation quantum yield of singlet oxygen(1O2).We successfully prepared crosslinked Ce6-doped Pdots by photocrosslinking reaction,they could prevent the leaching of photosensitizer,and improve the stability of photosensitizer in Pdots.In addition,we evaluated the cellular uptake,cytotoxicity,and photodynamic effect through cellular imaging,cell viability assay,lactate dehydrogenase(LDH)release assay,colony formation assay and cell staining.In vitro experiments indicated that the Ce6-doped Pdots could be easily internalized by cells for in vitro imaging and display apparent photodynamic effect under low incubation concentration and low dose of light irradiation.Meanwhile,we evaluated the biotoxicity and photodynamic effect through preparing tumor-bearing nude mice.In vivo experiments indicated that the Ce6-doped Pdots could effectively suppress solid tumor growth with little damage to important organs.2.We utilized the cell penetrating peptides to modify the Pdots with carboxyl groups,which could carry Pdots into cancer cells,promoting the cellular uptake of Pdots and enhancing the photodynamic therapeutic effect.In our studies,we prepared the photosensitizer zinc phthalocyanine(Zn Pc)doped Pdots(Zn Pc-doped Pdots),and modified with the cell penetrating peptides(R8),and finally obtained the stable R8-Pdots complex.R8-Pdots possessed with positive charge,particle size of 20-30 nm,good optical properties and high 1O2 generation quantum yield.We evaluated the cellular uptake,cytotoxicity,and photodynamic effect through cellular imaging,cell viability assay and cell staining.In vitro experiments indicated that R8 could obviously shorten the incubation time,promote the cellular uptake,and significantly enchance the photodynamic therapeutic effect.Meanwhile,we evaluated the biotoxicity and photodynamic effect through preparing tumor-bearing nude mice.In vivo experiments indicated that in contrast with carboxyl Pdots,intratumoral injection of R8-Pdots could enhance the photodynamic therapeutic effect and suppress the tumor growth to some extent.