Preparation Of Functionalized Polypyrrole Nanoparticles For Theranostic Treatment Of Tumor

Cancer is one of the most complex diseases in the world and has become a major threat to human health.The diagnostic and therapeutic methods used at present can no longer meet the growing clinical needs.There is an urgent need to develop new and effective methods for cancer diagnosis and treatment.By combining diagnosis and treatment,new nanomaterials with integrated functions of diagnosis and treatment have great application potential in the field of biomedicine.Nanoparticles with near-infrared(NIR)light responsive properties are a potential nanoplatform for cancer diagnosis and treatment.Firstly,it can be used for photoacoustic imaging.Secondly,it can transform NIR light into heat for photothermal treatment.In this paper,polypyrrole(PPy)nanoparticles(NPs)were used as a model to develop nanomaterials with photoacoustic imaging and photothermal therapy functions by utilizing their near-infrared(NIR)light response ability.The specific research contents are as follows:1.Firstly,PPy NPs of different sizes were prepared to study the effects of their sizes on photoacoustic imaging and photothermal therapy.PPy NPs were prepared by an one-step polymerization method with polyvinyl alcohol as stabilizer and ferric chloride as oxidant.PPy NPs with sizes of 40 nm,50 nm and 60 nm(named P40,P50 and P60,respectively)were successfully prepared by adjusting the concentration of polyvinyl alcohol.The formed PPy NPs were uniformly spherical with narrow distribution.The obtained PPy NPs showed obvious absorbance in the NIR region.It is found that P50 NPs had better photoacoustic imaging and photothermal conversion ability.At the same concentration,P50 NPs showed stronger photoacoustic signal.Under 808 nm laser irradiation,the heating effect of P50 NPs was more obvious,significantly higher than that of P40 and P60 NPs.The heating capacity of P50 NPs was proportional to their concentration and exhibited good photothermal stability.After laser irradiation,they can maintain similar morphology and optical properties.CCK8 test data showed that PPy NPs displayed obvious acute cytotoxicity under test conditions.After co-incubation for 2 or 6 hours,cell viability was significantly reduced.CCK8 detection and cell morphology observation confirmed that P50 NPs with concentrations ranging from 0 to 300 ppm had good cytocompatibility under the condition of 24 h co-incubation.Laser confocal observation showed that P50 NPs could be internalized by cells and mainly distributed in the cytoplasm after entering cells.After co-incubation with P50 NPs at 200 ppm for 12 h and laser treatment for 5 or 10 min,the P50 NPs showed significant photothermal therapy ability.In particular,after co-incubation with P50 NPs at 200 ppm,only about 10% of cells survived after laser irradiation for 5 or 10 min.The photothermal therapy effect of PPy NPs was further verified by labeling viable cells with Calcein-AM staining.2.PPy NPs were prepared and then modified with polydopamine and polyethylene glycol chains.The organic combination of PPy NPs and indocyanine green(ICG)was achieved by using the excellent modification ability of polydopamine and their abundant surface groups.The formed NPs were uniformly spherical in shape with a narrow size distribution range.The maximum loading ratio of PPy NPs to ICG was found by adjusting the mass feed ratio.The functionalized PPy NPs loaded with ICG(PPI NPs)exhibited strong photoacoustic imaging and photothermal properties under NIR light irradiation.At the same time,the NPs had good photothermal stability.After laser irradiation,they can maintain similar morphology and optical properties.ICG showed poor photothermal repeatability and photothermal stability under the same conditions.By flow cytometry test and laser confocal observation,the obtained NPs were well phagocytosed by HeLa cells and located in the cytoplasm.At the same time,CCK8 experiments showed that PPI NPs had good cytocompatibility after co-incubation for 24 or 48 h.PPI NPs had good blood compatibility without hemolysis.They were also able to stay in the HeLa cell tumor model in vivo,significantly enhancing the photoacoustic signal value at this site.Under the guidance of photoacoustic imaging,PPI NPs coupled with NIR laser can achieve good photothermal ablation effect.This effect is better than that of PPy NPs without ICG loading and control group.At the same time,during the treatment process,the organ section data of the experimental group and the weight monitoring data of the mice showed that this treatment method had no obvious side effects.These data indicate that the functionalized PPI NPs designed in this work have enhanced NIR response characteristics and have broad application prospects in the diagnosis and treatment of tumor.