Search

A combination of chemotherapy and photothermal therapy as a promising strategy has exhibited noticeable therapeutic effect on cancer therapy. To ensure the exertion of synergistic effect on a tumor region, a multifunctional vehicle for selectively delivering therapeutic agent into tumor cells is highly desirable. Thus, folate-poly (ethylene glycol)-distearoylphosphatidylcholine (FA-PEG-DSPE), cRGD [cyclic (Arg-Gly-Asp-D-Phe-Lys)]-PEG-DSPE and lecithin were employed to develop dual modified nanoparticles (FA/cRGD-PNPs) encapsulating polyaniline and cisplatin by a film-ultrasonic dispersion method. The FA/cRGD-PNPs showed a uniform size of 102.7 nm, remarkable stability and monodispersity, and highly localized temperature respond. Compared to chemo or photothermal treatment alone, the combined treatment on cellsin vitrosignificantly suppressed the survival rate of MDA-MB-231 cells (1.87%) and MGC-803 cells (2.37%) treated for 48 h. The results further indicated the induced cell apoptosis rate of MDA-MB-231 cells reached to 92.6% with treatment for 24 h. Hence, our research highlights the great potential in drug delivery and the combination of chemotherapy and photothermal therapy. [ABSTRACT FROM AUTHOR]

Synergistic therapy has caused increasing interest in recent treatment of cancer owing to its preferable therapeutic efficiency to most single antineoplastic protocol. Herein, we design a co-delivery two drugs nanosystem based on biodegradable liposomes, loading cisplatin, Indocyanine green (ICG), and CJM126 coupled with cholesterol derivative (CJM-Chol) for the purpose of synergistic therapy. The obtained nanoparticles showed a uniform diameter of 103.8 nm and a favorable morphology. The investigation on near infrared radiated (NIR) responsive release showed that NIR mediated photothermal conversion induced a controllable drug release from liposomes. Furthermore, the designed liposomes (only 50 μg/mL) displayed an inspiring photothermal conversion efficiency and received a high temperature (65.6 °C, Tm = 42 °C) when exposed to an 808 nm near infrared laser (1.54 W, 5 min). Besides, it turned out that the delivery system could be efficiently endocytosed by tumor cells, which attributed to its admirable biocompatibility and the targeting role of folate. The prepared nanoparticles showed significantly excellent inhibitory effect (3.05% cell viability in 24 h) on MDA-MB-231 cells when added irradiation as compared with free cisplatin (28.41%) or treatment without NIR (11.24%) in our study. Our research highlights the present nanoparticles provide a promising strategy for targeted delivery and photothermal treatment. [ABSTRACT FROM AUTHOR]

Dysregulated autophagy is involved in various human disorders including cancer. An autophagy-associated cell death pathway can be seen as a back-up cell death mechanism in cancer cells that are deficient in the apoptosis pathway. Therefore, many attempts have been made to induce autophagy for anticancer therapy. Anti-apoptotic Bcl-2 family proteins Bcl-2 and Bcl-xL can inhibit autophagy via binding to the BH3-only protein Beclin 1, an essential autophagy stimulator. In a previous study, we discovered several small molecule Beclin 1 mimetics as autophagy inducers through high-throughput screening and structural optimization, in which 3-nitroacridine warrants further exploration. Here, a series of novel 3-nitroacridine derivatives were designed, synthesized, and their pharmaceutical activities and mechanism of action were investigated against gastric cancer cell lines. As a result, compounds 3, 4, and 9 displayed potent cytotoxicity and induced autophagy in MGC-803 and SGC-7901 gastric cancer cells. Besides, compounds 3 and 9 also inhibited the migration of SGC-7901 cells. The development of 3-nitroacridine analogues as autophagy inducers is not only likely to be a potential strategy for cancer therapy, but it will also facilitate a better understanding of the complicated roles of autophagy in normal physiology and pathophysiology. [ABSTRACT FROM AUTHOR]

Cisplatin is a potent antitumor drug, which is widely applied in clinical cancer treatment. However, cisplatin can hardly distinguish between healthy tissue and tumor tissue, resulting in serious toxic side effects. Indocyanine green (ICG) is a FDA-approved near-infrared (NIR) fluorescence dye which has been used in photothermal therapy and optically mediated diagnostic, but the application of ICG is limited by its concentration-dependent aggregation, poor aqueous stabilityin vitro, lack of target specificity and rapid elimination from the body. Herein, to overcome these limitations of cisplatin and ICG, we fabricated folate-modified, cisplatin, ICG-loaded lipid-polymer hybrid nanoparticles (FCINPs) using a single-step sonication method. The FCINPs exhibited well-defined monodispersity, significant stability and excellent NIR penetration ability. The intracellular uptake experiment showed that the targeting efficacy of the FCINPs was more effective in folate receptors (FRs) over-expressing MCF-7 cells than FRs negative A549 cells. In addition, compared with chemo or photothermal treatment alone, the treatment of FCINPs in combination with 808 nm NIR laser irradiation can significantly induce the apoptosis and necrosis of MCF-7 cells. These findings indicated that the FCINPs would be a promising nanosized drug formulation for tumor-targeted therapy in the future. [ABSTRACT FROM PUBLISHER]

• NIR-elevated drug release realized intelligent drug delivery. • More therapeutic hydroxyl radical generated by GSH depletion-enhanced CDT. • The novel versatile Yolk-shell nanosystem achieved synergistic cancer therapy. In this study, a versatile doxorubicin (DOX)-loaded yolk-shell nano-particles (HMCMD) assembled with manganese dioxide (MnO 2) as the core and copper sulfide (HMCuS) as the mesoporous (∼ 6.4 nm) shell, was designed and synthesized. The resulting HMCMD possess excellent photothermal conversion efficiency. The DOX release from the yolk-shell nanoparticles could be promoted by laser irradiation, which increased the chemotherapy of DOX. Meanwhile, Mn2+ could be released from the HMCMD through a redox reaction between MnO 2 and abundant glutathione (GSH) in tumor cells. The released Mn2+ could promote the decomposition of the intracellular hydrogen peroxide (H 2 O 2) by Fenton-like reaction to generate the highly toxic hydroxyl radicals (·OH), thus exhibiting the effective chemodynamic therapy (CDT). Additionally, the efficiency of Mn2+-mediated CDT could be effectively enhanced by NIR irradiation. Further modification of polyethylene glycol (PEG) would improve the water solubility of the HMCMD to promote the uptake by MCF-7 cells. Hence, the HMCMD with synergistic effects of chemotherapy and chemodynamic/photothermal therapy would provide an alternative strategy in antitumor research. [ABSTRACT FROM AUTHOR]