A smart ATP-responsive chemotherapy drug-free delivery system using a DNA nanostructure for synergistic treatment of breast cancer in vitro and in vivo

Abstract Background: Combination of the prodrug technique with an albumin nanodrug-loaded system is a novel promising approach for cancer treatment. However, the long-lasting and far-reaching challenge for the treatment of cancers lies in how to construct the albumin nanometer drug delivery system with lead compounds and their derivatives. Results: In this study, we reported the preparation of injectable albumin nanoparticles (NPs) with a high and quantitative drug loading system based on the NabTM technology of paclitaxel palmitate (PTX-PA). Our experimental study on drug tissue distribution in vivo demonstrated that the paclitaxel palmitate albumin NPs (Nab-PTX-PA) remained in the tumor for a longer time post injection. Compared with saline and Abraxane® (nanoparticle albumin-bound (nab)-paclitaxel), intravenous injection of Nab-PTX-PA not only reduced the toxicity of the drug in normal organs and increased the body weight of the animals but maintained sustained release of paclitaxel (PTX) in the tumor, thereby displaying an excellent antitumor activity. Blood routine analysis showed that Nab-PTX-PA had fewer adverse effects or less toxicity to the normal organsand more importantly it inhibited tumor cell proliferation more effectively as compared with commercial Abraxane®.Conclusions: This carrier strategy for small molecule drugs is based on naturally evolved interactions between LCFAs(Long Chain Fatty Acids) and HSA(human serum albumin), demonstrated here for PTX. Nab-PTX-PA shows higher maximum tolerated doses and increased efficacy in vivo in breast cancer models, as compared to Abraxane for FDA-approved clinical formulations. This novel injectable Nab-PTX-PA platform has great potential as an effective drug delivery system in the treatment of breast cancer.

Download Full-text

Toxicity, Pharmacokinetics, And Antitumor Activity Study of a Novel Long-Acting Paclitaxel Nanodrug Delivery System Constructed On a Curcumin Derivative Carrier

10.21203/rs.3.rs-877478/v1 ◽

2021 ◽

Author(s):

chao Pi ◽

Mingtang Zeng ◽

Jingwen Ma ◽

Pu Guo ◽

Hongping Shen ◽

...

Keyword(s):

Breast Cancer ◽

Delivery System ◽

Average Particle Size ◽

Average Particle ◽

Cytotoxicity Test ◽

Nanodrug Delivery ◽

Cumulative Toxicity ◽

Curcumin Derivative

Abstract Purpose/Background: Paclitaxel (PTX) has been widely used in the clinic to treat breast cancer. However, its poor water solubility and intolerable toxicity greatly reduce the efficacy and medication safety. In this paper, a curcumin derivative (CUD) synthesized by the research group was used as a carrier to prepare a new type of PTX nanodrug delivery system (CUD-PTX-LN), thereby improving the safety of PTX medication and enhancing the anti-tumor effect.Methods: CUD-PTX-LN was prepared by solid dispersion technology and the dialysis method was adopted to investigate the release behavior of CUD-PTX-LN in vitro. Meanwhile, the dynamic process of nanoparticles in vivo was analyzed by pharmacokinetic experiments. Hemolysis experiment, acute toxicity and cumulative toxicity were conducted in mice to evaluate the safety of CUD-PTX-LN. Subsequently, the anti-tumor activity of CUD-PTX-LN was investigated using in vitro and in vivo breast cancer cell models.Results: The average particle size, PDI, and Zeta potential of CUD-PTX-LN were 238.5 ± 4.79 nm, 0.225 ± 0.011 and -33.8 ± 1.26 mV, respectively. CUD-PTX-LN had an encapsulation efficiency (%EE) of 94.20 ± 0.49% and an achievable drug loading (%DL) of 10.98 ± 0.31%. This nanoparticle was stable for up to half a year when the lyophilized powder was stored at room temperature. Cytotoxicity test on MCF-7 cells demonstrated the stronger cytotoxic activity of nanoparticles in comparison to free PTX. CUD-PTX-LN significantly prolonged the half-life and retention time of PTX. The area under the curve (AUC) of CUD-PTX-LN was 14.72 mg/L × h, which was 6 times that of the free PTX group (2.38 mg/L × h). In anti-tumor experiments in vivo, CUD-PTX-LN possessed the advantages of improving the antitumor efficacy and reducing the toxic side effects of drugs. Importantly, CUD-PTX-LN is safer than free PTX in terms of assessing hemolytic, acute and cumulative toxicity.Conclusion: A novel PTX nanodrug delivery system constructed based on CUD as a carrier holds great potential in improving breast cancer treatment.

Download Full-text

Novel luminescent silica nanoparticles (LSN): p53 gene delivery system in breast cancer in vitro and in vivo

Journal of Pharmacy and Pharmacology ◽

10.1111/j.2042-7158.2012.01547.x ◽

2012 ◽

Vol 68 (3) ◽

pp. 305-315 ◽

Cited By ~ 7

Author(s):

Chandrababu Rejeeth ◽

Ahmed Salem

Keyword(s):

Breast Cancer ◽

Gene Delivery ◽

Silica Nanoparticles ◽

Delivery System ◽

P53 Gene ◽

Gene Delivery System

Download Full-text

Combination of a novel growth hormone releasing hormone Antagonist JMR 132 and Tamoxifen enhances the inhibitory effects on growth of ZR 75 and T47D estrogen dependent human breast cancer cells in vitro and in vivo

Geburtshilfe und Frauenheilkunde ◽

10.1055/s-0029-1225201 ◽

2009 ◽

Vol 69 (05) ◽

Author(s):

S Buchholz ◽

AV Schally ◽

A Krishan ◽

A Papadia ◽

O Ortmann ◽

...

Keyword(s):

Breast Cancer ◽

Growth Hormone ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Growth Hormone Releasing Hormone ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Inhibitory Effects

Download Full-text

Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

Melatonin Research ◽

10.32794/mr11250042 ◽

2019 ◽

Vol 2 (4) ◽

pp. 83-98 ◽

Cited By ~ 2

Author(s):

André De Lima Mota ◽

Bruna Vitorasso Jardim-Perassi ◽

Tialfi Bergamin De Castro ◽

Jucimara Colombo ◽

Nathália Martins Sonehara ◽

...

Keyword(s):

Breast Cancer ◽

Glucose Metabolism ◽

Tumor Growth ◽

Tumor Cells ◽

Carbonic Anhydrases ◽

In Vivo Models ◽

Ca Ix ◽

Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression.

Download Full-text