One-Pot Preparation of Ultra-Small Lipid-Polymer Nanoparticles Loaded with Cis-Platinum to Combat Lung Cancer

2021 ◽  
Vol 11 (12) ◽  
pp. 2395-2400
Author(s):  
Yue-Jiao Cao ◽  
Zhi-Peng Li ◽  
Nan Zhou ◽  
Jia-Ping Liu

The cis-platinum (CDDP) is a first line chemotherapeutics drugs to combat lung cancer. However, its efficacy is largely limited due to the off-target delivery and multidrug resistance (MDR) upon in vivo applications. In order to solve this problem, here in our study, we prepared ultra-small lipidpolymer nanoparticles (USLPNPs) using one-pot method and to load CDDP (USLPNPs-CDDP) for the effective lung cancer therapy. Our results showed that the size of USLPNPs-CDDP was 20 nm and the stability of this platform was high. The sustained drug release afforded the long-lasting administration of CDDP to treat cancers. Most importantly, the USLPNPs-CDDP was able to bypass the CDDP resistance of A549/CDDP cells, which resulted in better anticancer benefits as compared to free CDDP both in vitro and in vivo.

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Jinyuan He ◽  
Chulian Gong ◽  
Jie Qin ◽  
Mingan Li ◽  
Shaohong Huang

Abstract Current cancer therapy usually succumbs to many extracellular and intracellular barriers, among which untargeted distribution and multidrug resistance (MDR) are two important difficulties responsible for poor outcome of many drug delivery systems (DDS). Here, in our study, the dilemma was addressed by developing a cancer cell membrane (CCM)-coated silica (SLI) nanoparticles to co-deliver miR495 with doxorubicin (DOX) for effective therapy of lung cancer (CCM/SLI/R-D). The homologous CCM from MDR lung cancer cells (A549/DOX) was supposed to increase the tumor-homing property of the DDS to bypass the extracellular barriers. Moreover, the MDR of cancer cells were conquered through downregulation of P-glycoprotein (P-gp) expression using miR495. It was proved that miR495 could significantly decrease the expression of P-gp which elevated intracellular drug accumulation in A549/DOX. The in vitro and in vivo results exhibited that CCM/SLI/R-D showed a greatly enhanced therapeutic effect on A549/DOX, which was superior than applying miR495 or DOX alone. The preferable effect of CCM/SLI/R-D on conquering the MDR in lung cancer provides a novel alternative for effective chemotherapy of MDR cancers.


Author(s):  
Hui Liu ◽  
Chunlei Guo ◽  
Yuhong Shang ◽  
Lin Zeng ◽  
Haixue Jia ◽  
...  

In recent years, supramolecular nanoparticles consisting of peptides and drugs have been regarded as useful drug delivery systems for tumor therapy. Pemetrexed (PEM) is a multitarget drug that is effective for many cancers, such as non-small cell lung cancer. Here, RGD-conjugated molecular nanoparticles mainly composed of an anticancer drug of PEM (PEM-FFRGD) were prepared to deliver PEM to tumors. The peptide could self-assemble into a nanoparticle structure with diameter of about 20 nm. Moreover, the nanoparticle showed favorable solubility and biocompatibility compared with those of PEM, and the MTT test on A549 and LLC cells showed that the PEM-FFRGD nanoparticles had stronger cytotoxic activity than PEM alone. Most importantly, the nanoparticle could promote tumor apoptosis and decrease mitochondrial energy metabolism in tumors. In vivo studies indicated that PEM-FFRGD nanoparticles had enhanced antitumor efficacy in LLC tumor-bearing mice compared to that of PEM. Our observations suggested that PEM-FFRGD nanoparticles have great practical potential for application in lung cancer therapy.


Nanomedicine ◽  
2020 ◽  
Vol 15 (27) ◽  
pp. 2689-2705
Author(s):  
Ming-Hsien Chan ◽  
Yung-Chieh Chan ◽  
Ru-Shi Liu ◽  
Michael Hsiao

Aim: To develop a micelle-type nanobubble decorated with fluorescein-5-isothiocyanate-conjugated transferrin, with encapsulation of paclitaxel (PTX@FT-NB) for lung cancer treatment. Materials & methods: PTX@FT-NBs were characterized to determine their physicochemical properties, structural stability and cytotoxicity. Lung cancer cell and mouse xenograft tumor models were used to evaluate the therapeutic effectiveness of PTX@FT-NB. Results: The PTX@FT-NBs not only showed selective targeting to lung cancer cells but also inhibited tumor growth significantly via paclitaxel release. Furthermore, paclitaxel-induced microtubule stabilization demonstrated the release of the drug from PTX@FT-NB in the targeted tumor cell both in vitro and in vivo. Conclusion: PTX@FT-NB has the potential as an anticancer nanocarrier against lung cancer cells because of its specific targeting and better drug delivery capacity.


Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2989 ◽  
Author(s):  
Wan Nur Baitty Wan Mohd Tajuddin ◽  
Nordin H. Lajis ◽  
Faridah Abas ◽  
Iekhsan Othman ◽  
Rakesh Naidu

Lung cancer is among the most common cancers with a high mortality rate worldwide. Despite the significant advances in diagnostic and therapeutic approaches, lung cancer prognoses and survival rates remain poor due to late diagnosis, drug resistance, and adverse effects. Therefore, new intervention therapies, such as the use of natural compounds with decreased toxicities, have been considered in lung cancer therapy. Curcumin, a natural occurring polyphenol derived from turmeric (Curcuma longa) has been studied extensively in recent years for its therapeutic effects. It has been shown that curcumin demonstrates anti-cancer effects in lung cancer through various mechanisms, including inhibition of cell proliferation, invasion, and metastasis, induction of apoptosis, epigenetic alterations, and regulation of microRNA expression. Several in vitro and in vivo studies have shown that these mechanisms are modulated by multiple molecular targets such as STAT3, EGFR, FOXO3a, TGF-β, eIF2α, COX-2, Bcl-2, PI3KAkt/mTOR, ROS, Fas/FasL, Cdc42, E-cadherin, MMPs, and adiponectin. In addition, limitations, strategies to overcome curcumin bioavailability, and potential side effects as well as clinical trials were also reviewed.


2022 ◽  
Vol 12 (4) ◽  
pp. 690-694
Author(s):  
Wei Zhang ◽  
Yi Chen ◽  
Bin Wang ◽  
Xueren Feng ◽  
Lijuan Zhang ◽  
...  

Lung cancer is a worldwide issue which account for the death of thousands every year. Paclitaxel (PTX) as the first line chemotherapy drug to treat lung cancer, its clinical applications is largely limited by its poor solubility. The facile preparation of pharmaceutical formulations to increase the solubility as well as targetability of PTX is of vital importance in lung cancer treatment. Herein, we introduced a facile method to prepare PTX nano-suspensions (NSs), which have high drug loading as well as well-dispersed particle size. The in vitro cell experiments revealed its capability to enhance the drug accumulation in A549 cells than free PTX. Moreover, in vivo animal assay suggested its better tumor accumulation and antitumor efficacy than PTX injection (Taxol).


2021 ◽  
Author(s):  
Xijie Yang ◽  
Zhen Zeng ◽  
Xiaohua Jie ◽  
Ye Wang ◽  
Jun Han ◽  
...  

Abstract BackgroundRadioresistance is regarded as the main cause of local recurrence and distant metastasis in lung cancer. However, the underlying mechanisms of radioresistance remain incompletely understood. This study investigates the roles and regulatory mechanisms of arginine methyltransferase PRMT5 in lung cancer radioresistance.MethodsImmunoprecipitation assay and GST pulldown were used to detect the protein-protein interaction. The methylation of Mxi1 was determined by in vivo and in vitro arginine methylation assays. In vivo ubiquitination and CHX chase assays were performed to examine the stability of Mxi1. The biological effects of PRMT5 and its specific inhibitor EPZ015666 in lung cancer were evaluated both in vitro and in vivo.ResultsWe show that the arginine methyltransferase PRMT5 interacts with and methylates Mxi1, which promotes the binding of the β-Trcp ligase to Mxi1, facilitating the ubiquitination and degradation of Mxi1 in lung cancer. Furthermore, genetic blockade of PRMT5 impairs DNA damage repair and enhances lung cancer radiosensitivity in vitro and in vivo, and these phenotypes are partially reversed by Mxi1 silencing. More importantly, pharmacological inhibition of PRMT5 with the specific inhibitor EPZ015666 leads to extraordinary radiosensitization in vitro and in vivo in lung cancer.ConclusionsOur data indicate that PRMT5 methylates and destabilizes Mxi1 to confer radioresistance, suggesting that PRMT5 may be a promising radiosensitization target in lung cancer.


2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Yanxia Ma ◽  
Yu Liu ◽  
Linxin Teng ◽  
En Luo ◽  
Dekang Liu ◽  
...  

Lung cancer has become the leading cause of cancer-related death worldwide. Oxidative stress plays important roles in the pathogenesis of lung cancer. Many natural products show antioxidative activities in cancer treatment. Zi Shen decoction (ZSD) is a classic prescription for the treatment of lung disease. However, its effect on lung cancer lacks evidence-based efficacy. In this study, we investigated the anticancer effects of ZSD on lung cancer in vivo and in vitro. Our results showed that oral administration of ZSD suppressed the Lewis lung cancer (LLC) growth in a subcutaneous allograft model and promoted necrosis and inflammatory cell infiltration in the tumor tissues. Furthermore, ZSD not only inhibited tumor cell proliferation and migration but also induced cell apoptosis in lung cancer cells. PI3K/AKT signaling is well characterized in response to oxidative stress. The bioinformatics analysis and western blot assays suggested that ZSD decreased the enzyme activity of PI3K and AKT in vivo and in vitro. We also found that the AKT/GSK-3β/β-catenin pathway medicated anticancer effect of ZSD in lung cancer cells. In conclusion, we demonstrate for the first time that ZSD possesses antitumor properties, highlighting its potential use as an alternative strategy or adjuvant treatment for lung cancer therapy.


Author(s):  
Robert J. Carroll ◽  
Marvin P. Thompson ◽  
Harold M. Farrell

Milk is an unusually stable colloidal system; the stability of this system is due primarily to the formation of micelles by the major milk proteins, the caseins. Numerous models for the structure of casein micelles have been proposed; these models have been formulated on the basis of in vitro studies. Synthetic casein micelles (i.e., those formed by mixing the purified αsl- and k-caseins with Ca2+ in appropriate ratios) are dissimilar to those from freshly-drawn milks in (i) size distribution, (ii) ratio of Ca/P, and (iii) solvation (g. water/g. protein). Evidently, in vivo organization of the caseins into the micellar form occurs in-a manner which is not identical to the in vitro mode of formation.


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