Melanoma has been a serious threat to the human health;however,effective therapeutic methods of this cancer are still limited.Combined local therapy is a crucial approach for achieving a superior anti-tumor efficacy.In this paper,a chemo-immunotherapy system of DOX,IL-2 and IFN-g based on poly(g-ethyl-Lglutamate)-poly(ethylene glycol)-poly(g-ethyl-L-glutamate)(PELG-PEG-PELG)hydrogel was developed for local treatment of melanoma xenograft.The drug release process of this system exhibited a short term of burst release(the first 3 days),followed by a long-term sustained release(the following 26 days).The hydrogel degraded completely within 3 weeks without obvious inflammatory responses in the subcutaneous layer of rats,showing a good biodegradability and biocompatibility.The DOX/IL-2/IFN-g co-loaded hydrogel also showed enhanced anti-tumor effect against B16F10 cells in vitro,through increasing the ratio of cell apoptosis and G2/S phage cycle arrest.Moreover,the combined strategy presented improved therapy efficacy against B16F10 melanoma xenograft without obvious systemic side effects in a nude mice model,which was likely related to both the enhanced tumor cell apoptosis and the increased proliferation of the CD3t/CD4t T-lymphocytes and CD3t/CD8t T-lymphocytes.Overall,the strategy of localized co-delivery of DOX/IL-2/IFN-g using the polypeptide hydrogel provided a promising approach for efficient melanoma therapy.
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.
Gold nanoparticles have seen unprecedented development in the biomedical field, particularly for cancer ther- apy. They have received extensive attention because of their easy preparation, functionalization, biocompatibility, non-cytotoxicity, and detectability. Functionalized gold nanoparticles can be applied in the fields of drug and gene delivery, photothermal therapy, and bioimaging. This review introduces methods for preparing various shapes of gold nanoparticles and describes their current applications in the field of cancer treatment. Moreover, the review presents the development routes and current issues of gold nanoparticles in clinical theranostics.
Herein, cisplatin-loaded poly（L-glutamic acid）-g-methoxy poly（ethylene glycol） nanoparticles were evaluated as a potential chemotherapeutic agent against osteosarcoma by using alone or with an i RGD（internalizing RGD, CRGDKDPDC）. The release rate of platinum from the cisplatin-loaded nanoparticles CDDP/PLG160-g-m PEG2K（CDDP-NPs） accelerated with the increase of the acidity of the environment. In vitro test demonstrated that CDDP-NPs could inhibit the proliferation of MNNG/Hos osteosarcoma cells with IC50（72 h） of 12.2 μg·mL^-1. In vivo test for MNNG/Hos osteosarcoma tumor bearing mice exhibited that CDDP-NPs had comparable or slightly higher efficacy but significantly lower side effects in comparison with free CDDP. The coadministration of i RGD could further enhance the anticancer efficacy of CDDP-NPs against MNNG/Hos osteosarcoma without bringing obvious side effects. Therefore, CDDP-NPs using alone or with iRGD have great potential for the treatment of osteosarcoma.
Nano-therapeutic approach for clinical implementation of tumors remains a longstanding challenge in the medical field. The main challenges are rapid clearance, offtarget effect and the limited role in the treatment of metastatic tumors. Toward this objective, a cell-mediated strategy by transporting photothermal reagents and CpG adjuvant within macrophage vehicles is performed. The photothermal reagents are constructed by conjugating of hyperbranched polyethyleimine（PEI） to golden nanorode（GNR） via S-Au bonds.GNR-PEI/CpG nanocomposites, formed via electrostatic interaction and displayed excellent near-infrared（NIR） photothermal performance, exhibit immense macrophage uptake and negligible cytotoxic effect, which is essential for the fabrication of GNR-PEI/CpG loaded macrophages. GNR-PEI/CpG loaded macrophages demonstrated admirable photothermal response in vitro. Benefited from the functionalization of the binding adhesion between macrophages and 4 T1 cells, GNR-PEI/CpG loaded macrophages significantly promoted tumor accumulation in vivo and dramatically enhanced the efficiency of photothermal cancer therapy. Moreover, the immune system is activated after photothermal therapy, which is mainly attributed to the generation of tumor specific antigens and CpG adjuvant in situ. Our findings provide a potential cell-mediated nanoplatform for tumor therapy by combination of near infrared photothermal therapy and immunotherapy.
Jie ChenLin LinNan YanYingying HuHuapan FangZhaopei GuoPingjie SunHuayu TianXuesi Chen
In recent years,various carriers for gene delivery nave been developed for biomedical applications.Among all kinds of gene carriers,cationic polymeric carriers for delivery therapeutic gene as non-viral carriers have received growing interests due to their improved high transfection efficiency with the relative safety.In particular,the advancement of novel polymeric gene carriers has gained much progress in the development of effective anticancer therapy.Herein,this review focused on the development of cationic polymeric carriers for cancer therapy,including polyethylenimine(PEI),polyamidoamine(PAMAM) dendrimers,polylysine(PLL),chitosan and modified cationic polymers.And recent progresses in the development of novel polymeric carriers for gene delivery,such as targeted gene carriers,responsive gene carriers and multifunctional gene carriers,were summarized.Finally,the future perspectives in the development of novel polymeric carriers for delivery gene were presented.
