<p>Synergistic Combination Chemotherapy of Lung Cancer: Cisplatin and Doxorubicin Conjugated Prodrug Loaded, Glutathione and pH Sensitive Nanocarriers</p>

Abstract

Prodrug technology-based combination drug therapy has been exploited as a promising treatment strategy to achieve synergistic lung cancer therapy, reduce drug dose, and decrease side effects. In the present study, we synthesized a pH and glutathione (GSH) sensitive prodrug, cisplatin (CIS) and doxorubicin (DOX) conjugates (CIS-DOXp). CIS-DOXp was loaded by nanocarriers and delivered into the tumor site. Methods: pH and GSH sensitive CIS-DOX prodrug (CIS-DOXp) was synthesized by conjugating GSH responsive CIS prodrug with pH sensitive DOX prodrug. CIS-DOXp-loaded nanocarriers (CIS-DOXp NC) were prepared using emulsification and solvent evaporation method. The morphology, particle size, polydispersity index (PDI) and zeta potential of nanocarriers were measured. In vitro cytotoxicity of nanocarriers and the corresponding free drugs was examined using the MTT assay. In vivo anti-tumor efficiency and biodistribution behaviors were evaluated on lung cancer mice models. Results: The size, PDI, zeta potential, CIS loading efficiency, and DOX loading efficiency of CIS-DOXp NC were 128.6 ± 3.2 nm, 0.196 ± 0.021, 15.7 ± 1.7 mV, 92.1 ± 2.1%, and 90.4 ± 1.8%, respectively. The best cell killing ability (the lowest combination index of 0.57) was found at the combination ratio of 1:3 (CIS:DOX, w/w) in the drugs co-loaded formulations, indicating the strongest synergism effect. CIS-DOXp NC showed the best tumor inhibition efficiency (79.9%) in mice with negligible body weight lost. Conclusion: CIS-DOXp NC could be applied as a promising system for the synergistic chemotherapy of lung cancer.

Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

“…At present, lung cancer remains the main cause of cancer-related death worldwide, ranking first in cancer mortality in men and second in women [ 25 , 26 ]. According to the WHO statistics, there were about 2.1 million new lung cancer cases and 1.8 million cancer deaths in 2018, accounting for 11.6% of the total new cancer cases and 18.4% of the total cancer deaths, respectively, and the 5-year survival rate was only 10% to 20% [ 27 ]. In recent years, immunotherapy has become an emerging hot spot in lung cancer treatment, in which programmed cell death receptor1 (PD-1) and immunocheckpoint inhibitors represented by PD-L1 inhibitors have made breakthroughs in the treatment of lung cancer [ 28 ].…”

Prostate Cancer Therapy Using Docetaxel and Formononetin Combination: Hyaluronic Acid and Epidermal Growth Factor Receptor Targeted Peptide Dual Ligands Modified Binary Nanoparticles to Facilitate the in vivo Anti-Tumor Activity

“…FMN-loaded HA-NPs (HA-FMN-NPs, Figure 1B ) were prepared using a solvent evaporation method. 26 HA-PEG-DSPE (100 mg), soya lecithin (50 mg), and FMN (30 mg) were dissolved in chloroform (5 mL) to produce the organic phase, and then added dropwise into 15 mL Milli-Q water containing DDAB (1% w/v) under gentle stirring (400 rpm). Then the mixture was stirred for 10 h to evaporate the organic solvent to obtain HA-FMN-NPs.…”

Acute myocardial infarction therapy: in vitro and in vivo evaluation of atrial natriuretic peptide and triphenylphosphonium dual ligands modified, baicalin-loaded nanoparticulate system

“…Flow rate was kept at 0.5 mL/min and system was maintained at 35 °C, the detection was carried out at λ = 278 nm. EE and DL were calculated according to the following formulas (Jin et al., 2020 ): EE (%)=(weight of loaded drug/weight of feeding drug)×100; DL (%)=(weight of loaded drug/weight of drugs loaded LPNs)×100.…”

“…Stability of LPNs was evaluated by observing the appearance and diameter of the systems during the storage time (until 90 days) at the temperature of 2–8 °C (Jin et al., 2020 ).…”