Modulating the Oxidation Degree of Linear Polyethyleneimine for Preparation of Highly Efficient and Low-cytotoxicity Degradable Gene Delivery Carriers

Polyethyleneimine(PEI),as a widely used polymer material in the field of gene delivery,has been extensively studied for modification and shielding to reduce its cytotoxicity.However,research aimed at preparing degradable PEI is scarce.In this work,the hydrogen peroxide(H_(2)O_(2))oxidation method was used to introduce degradable amide groups in the PEI and a series of oxidized PEI22k(oxPEI22k)with different degrees of oxidation were synthesized by regulating the dosage of H_(2)O_(2).The relationship between the oxidation degree of oxPEI22k and the gene transfection efficiency of oxPEI22k was studied in detail,confirming that the oxPEI22k with oxidation degrees of 16.7%and 28.6%achieved improved transfection efficiency compared to unmodified PEI.These oxPEI22k also proved reduced cytotoxicity and improved degradability.Further,this strategy was extended to the synthesis of low-molecular-weight oxPEI1.8k.The oxPEI1.8k with suitable oxidation degree also achieved improved transfection efficiency and reduced cytotoxicity.In brief,this work provided high-efficiency and low-cytotoxicity degradable gene delivery carriers by regulating the oxidation degree of PEI,which was of great significance for promoting clinical applications of PEI.

PLG-g-mPEG Mediated Multifunctional Nanoparticles for Photoacoustic Imaging Guided Combined Chemo/Photothermal Antitumor Therapy

Under laser irradiation,photothermal therapy(PTT)effectively ablates tumors above 50℃.However,hyperthermia can cause additional damage due to the inevitable heat spread to surrounding healthy tissue.Herein,nanoparticles named as GI@P NPs were designed for enhanced PTT with heat shock protein 90(HSP90)inhibition at temperatures below 50℃to achieve optimal cancer therapy and avoid surrounding damage.GI@P NPs were done by co-loading Garcinia cambogia acid(GA)and photosensitizer IR783 in polymer PLG-g-mPEG to form a nanomedicine,where IR783 with excellent photoacoustic(PA)signal acted as an excellent photothermal therapeutic agent that converted the laser energy into heat to kill tumor cells,GA was used as antitumor drug for chemotherapy and an inhibitor of HSP90 to overcome the heat resistance of tumors for efficient cryo-photothermal therapy,and PLG-g-mPEG can encapsulate IR783 and GA to increase biocompatibility and accumulate effectively in the tumor.After GI@P NPs were injected into the mice,we could observe that the PA signals gradually increased in the tumor region and showed the strongest PA signals at 12 h.Under laser irradiation,the tumor temperature of the mice could raise to about 43.5℃,and the tumor was significantly inhibited after long-term monitoring by PA imaging.As a result,gentle PTT produced by GI@P NPs exhibited good antitumor effects at relatively low temperature and minimized nonspecific thermal damage to normal tissues.The GI@P NPs as nanomedicine enriched our understanding of various applications of polymeric carriers,especially in the biomedical field.

Anti-tumor effects of combined doxorubicin and siRNA for pulmonary delivery

Direct administration of drugs and genes to the lungs by pulmonary delivery offers a potential effective therapy for lung cancers.In this study,combined doxorubicin（DOX） and Bcl2 siRNA was employed for cancer therapy using polyethylenimine（PEI） as the carrier of Bcl2 siRNA.Most of the DOX and siRNA possessed high cellular uptake efficiency in B16F10 cells,which was proved by FCM and CLSM analysis.Real-time PCR showed that PEI/Bcl2 siRNA exhibited high gene silencing efficiency with 70%Bcl2 mRNA being knocked down.The combination of DOX and siRNA could enhance the cell proliferation inhibition and the cell apoptosis against B16F10 cells compared to free DOX or PEI/Bcl2 siRNA.Furthermore,the biodistribution of DOX and siRNA via pulmonary administration was studied in mice with B16F10 metastatic lung cancer.The results showed that most of the DOX and siRNA were accumulated in lungs and lasted at least for 3 days,which suggested that combined DOX and siRNA by pulmonary administration may have high anti-tumor effects for metastatic lung cancer treatment in vivo.