Polydopamine Relative Nanoparticles In The Treatment Of Prostate Cancer

Prostate cancer(PCa)is one of the most common tumors in urinary system.It threats men’s health seriously.In the US,the morbidity ranks first and mortality ranks second among malignant tumors in male.In China,the incidence of PCa is lower than developed country,but increases fast recently.PCa is still a difficult problem in clinical diagnosis and treatment,especially for castration-resistant PCa(CRPC),which is one of the concerns of urologists around the world.Nowadays more and more kinds of nanomaterials have been applied in the research of cancer treatment.With the enhanced permeability and retention(EPR)effect,nanoparticles can accumulate in tumor easily.Some nanomaterials are photosensitizing agents,which can destruct the tumor cells strongly via photothermal effect.Different from common metal or semiconductor photosensitizing agents,the novel nanoparticles are great of biocompatibility and optical stability.They have high light-thermal conversion efficiency and low biotoxicity as well.Dopamine is one of common neurotransmitter in clinical treatment.Polydopamine(PDA)easily self-assembled with oxypolymerization of monomer dopamine.It has excellent histocompatibility and biosecurity and is able to convert near infrared reflection(NIR)to thermal energy efficiently.In this study,PDA is developed as a promising carrier.We presented(1)cisplatin conjugated PDA nanoparticles and(2)pH responsive doxorubicin loaded PDA nanoparticles,combining chemotherapy and photothermal therapy to treat prostate cancer cells and human prostate tumor mouse xenograft model.(1)We established PDA-polyethylene glycol-cisplatin nanoparticles[Pt(Ⅳ)-PDA NP].Cisplatin is one of the commonly used anti-tumor drugs in clinical practice.It is easily to be modified and can be oxidized to Pt(IV)prodrug,which will release cisplatin upon intracellular reduction.Original PDA NPs were combined of oxidized cisplatin with PEG and the size of final NPs was around 70nm.We described the characterization of the NPs.The Pt(IV)prodrug was reduced under physiological reducing environment.The temperature of NP solution could increase quickly under NIR exposure.We evaluated the cytotoxicity against PCa cells in vitro,as well as biodistribution and antitumor effect in human prostate tumor mouse xenograft model.(2)We established PDA-polyallylamine hydrochloride-citraconic anhydride-doxorubicin nanoparticles(Dox@PAH-cit/PDA NP).PAH-cit is one kind of pH responsive polymer for the charge can be readily converted from negative to positive through side-chain hydrolysis upon exposure to acid solutions.At low pH,the loaded Dox was released from the NP because of amide hydrolysis of PAH-cit.In vivo the acidic environment could be found within late endosomes and lysosomes in tumor cells so the drugs were released in the tumor site.The size of this NP was around 80nm.Similarly,we evaluated the antitumor effect in vitro and in vivo.As the result,both of these two drug delivery systems,which were based on PDA as carriers,had excellent light-thermal conversion efficiency.Upon the NIR exposure(808nm),the temperature of the NP solution could increase fast to kill tumor cells.Compared with free chemotherapy drugs,the NPs had stronger cell uptake ability.In vivo the PDA NPs could brilliantly accumulate in tumor location.After intravenous administration and NIR exposure,we succeeded to inhibit the tumor growth.In summary,we provided a type of PDA drug delivery system that was promising for future clinical cancer treatment.