RESUMO
In this study, we aim to develop a pH-sensitive transmembrane peptide TH (AGYLLGHINLHH LAHL(Aib)HHIL-Cys) modified liposome loaded with immunoadjuvant α-galactosylceramides (αGC-TH- Lip) and then investigate its effect on the immune function in tumor-bearing mice and its immune mechanism of action. The liposomes were prepared by membrane dispersion-probe ultrasound method and the size and zeta potential of αGC-TH-Lip were also characterized. The uptake of TH modified liposomes (TH-Lip) and polyethylene glycols modified liposomes (PEG-Lip) in DC2.4 cells in vitro were analyzed and the activation of natural killer T (NKT), natural killer (NK) and macrophages in tumor-bearing mice were also measured after systemic administrations of samples. Besides, the degree of maturation of dendritic cell (DC), the number of cytotoxic T lymphocyte (CTL) and the differentiation of helper T cell (Th) were determined. The results showed the particle size of αGC-TH-Lip was about 117.9 nm and the zeta potential was about -8.37 mV under the neutral condition (pH 7.4) and the αGC-TH-Lip had high serum stability in 50% fetal bovine serum. The uptake of TH-Lip in DC2.4 cells in vitro was 1.48 times higher than that of PEG-Lip. After systemic administrations of the samples, the numbers of NKT cells, NK cells and macrophages in tumor-bearing mice were (0.43±0.048)%, (12.80±0.50)% and (3.13±0.26)%, respectively, and the number of mature DCs and CTLs reached (2.30±0.22)% and (32.30±0.80)% separately, which was significantly different from the con-trol group. Finally, we discovered the αGC-TH-Lip had the strongest induction effect on the differentiation of Th1 cells, while barely promote the differentiation of Th2 cells. All the above results demonstrated that the αGC-TH-Lip can improve the immune the activity of mice, enhance the effect of α-galactosylceramide and promote the differentiation of lymphocytes toward the direction of cellular immunity, which consequently achieve a better anti-cancer immune activity.
RESUMO
In this study, we used low molecular weight heparin (LH) as hydrophilic sides, doxorubicin (DOX) as hydrophobic sides, and indocyanine green (ICG) as a photosensitive drug to prepare pH-sensitive self-assembled polymeric micelles (LH-DOX/ICG). The micelles were prepared by dialysis, and evaluated for stability, pH sensibility in vitro, hemolytic test and photo-thermal effect. Wound healing test was used to evaluate the anti-metastatic effects. MTT assay and apoptosis detection kit were used to evaluate the cytotoxicity of micelles against melanoma B16F10 cells. The size of the micelles was (148.7 ±2.1) nm and the zeta potential was (-30.7 ±1.1) mV. The drug-loading content of DOX and ICG were 11.82% and 5.59%, respectively. The micelles exhibited spherical in shape, fairly uniform size. The micelles were stable within 48 h in 50% fetal bovine serum phosphate buffer. The release of DOX was pH-sensitive, while the release of ICG was sustained. The micelles were biocompatible and safe as indicated by the hemolytic test. In vitro photo-thermal effect indicated LH-DOX/ICG micelles had similar photo-thermal effect to the free ICG. Wound healing test showed that the micelles had a good ability to inhibit tumor migration with laser irradiation. MTT assay and cell apoptosis assay indicated that LH-DOX/ICG micelles displayed more efficient anti-tumor effect after near infrared laser compared to LH-DOX micelles. LH-DOX/ICG micelles are promising for the therapeutic effect of phototherapy and chemotherapy in combination for melanoma.
RESUMO
Strontium carbonate nanoparticles (SCNs), a novel biodegradable nanosystem for the pH-sensitive release of anticancer drugs, were developed via a facile mixed solvent method aimed at creating smart drug delivery in acidic conditions, particularly in tumor environments. Structural characterization of SCNs revealed that the engineered nanocarriers were uniform in size and presented a dumbbell-shaped morphology with a dense mass of a scale-like spine coating, which could serve as the storage structure for hydrophobic drugs. Chosen as a model anticancer agent, etoposide was effectively loaded into SCNs based on a simultaneous process that allowed for the formation of the nanocarriers and for drug storage to be accomplished in a single step. The etoposide-loaded SCNs (ESCNs) possess both a high loading capacity and efficient encapsulation. It was found that the cumulative release of etoposide from ESCNs is acid-dependent, and that the release rate is slow at a pH of 7.4; this rate increases significantly at low pH levels (5.8, 3.0). Meanwhile, it was also found that the blank SCNs were almost nontoxic to normal cells, and ESCN systems were evidently more potent in antitumor activity compared with free etoposide, as confirmed by a cytotoxicity test using an MTT assay and an apoptosis test with fluorescence-activated cell sorter (FACS) analysis. These findings suggest that SCNs hold tremendous promise in the areas of controlled drug delivery and targeted cancer therapy.
Assuntos
Carbonatos/química , Preparações de Ação Retardada/síntese química , Etoposídeo/administração & dosagem , Etoposídeo/química , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Neoplasias Experimentais/tratamento farmacológico , Estrôncio/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Humanos , Concentração de Íons de Hidrogênio , Nanocápsulas/ultraestrutura , Neoplasias Experimentais/patologia , Tamanho da Partícula , Resultado do TratamentoRESUMO
Bulk fabrication of ordered hollow structural particles (HSPs) with large surface area and high biocompatibility simultaneously is critical for the practical application of HSPs in biosensing and drug delivery. In this article, we describe a smart approach for batch synthesis of calcium carbonate nanotubes (CCNTs) based on supported liquid membrane (SLM) with large surface area, excellent structural stability, prominent biocompatibility, and acid degradability. The products were characterized by transmission electron micrograph, X-ray diffraction, Fourier transform infrared spectra, UV-vis spectroscopy, zeta potential, and particle size distribution. The results showed that the tube-like structure facilitated podophyllotoxin (PPT) diffusion into the cavity of hollow structure, and the drug loading and encapsulation efficiency of CCNTs for PPT are as high as 38.5 and 64.4 wt.%, respectively. In vitro drug release study showed that PPT was released from the CCNTs in a pH-controlled and time-dependent manner. The treatment of HEK 293T and SGC 7901 cells demonstrated that PPT-loaded CCNTs were less toxic to normal cells and more effective in antitumor potency compared with free drugs. In addition, PPT-loaded CCNTs also enhanced the apoptotic process on tumor cells compared with the free drugs. This study not only provides a new kind of biocompatible and pH-sensitive nanomaterial as the feasible drug container and carrier but more importantly establishes a facile approach to synthesize novel hollow structural particles on a large scale based on SLM technology.