scholarly journals A Supramolecular Nanoparticle of Pemetrexed Improves the Anti-Tumor Effect by Inhibiting Mitochondrial Energy Metabolism

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.

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.


2018 ◽  
Vol 01 (03) ◽  
pp. 213-218 ◽  
Author(s):  
Linwei Lu ◽  
Zhengxiao Zhao ◽  
Lumei Liu ◽  
Weiyi Gong ◽  
Jingcheng Dong

Objective: The objective of this study is to preliminarily evaluate the efficacy of the combination of baicalein and docetaxel on non-small cell lung cancer (NSCLC) in vivo. Methods: The subcutaneous model was established by inoculation of A549 cells, and then these tumor-bearing mice were randomly assigned to eight groups to receive normal saline (NS) as control, baicalein alone, Taxotere[Formula: see text] (docetaxel injection) alone or the combination of baicalein and Taxotere[Formula: see text]. The effect of the combination treatment was evaluated by [Formula: see text] value. Tumors were harvested for TUNEL and CD31 immunohistochemical staining and important organs for H&E staining. Results: Baicalein 50[Formula: see text]mg/kg plus docetaxel 10[Formula: see text]mg/kg significantly reduced tumor weight and inhibited the growth rate of tumor, displaying the additive effect indicated by the [Formula: see text] value. Increased apoptosis and decreased tumor angiogenesis also provided pathological evidence. Additionally, baicalein 50[Formula: see text]mg/kg plus docetaxel 10[Formula: see text]mg/kg did not increase toxicity in lung, liver and kidney. Conclusion: Baicalein 50[Formula: see text]mg/kg plus docetaxel 10[Formula: see text]mg/kg additively inhibits the growth of NSCLC in vivo, and the mechanism underlying remains to be discovered.


2014 ◽  
Vol 31 (7) ◽  
pp. 656-657
Author(s):  
V. Jeannot ◽  
S. Mazzaferro ◽  
J. Lavaud ◽  
V. Josserand ◽  
M. Guidetti ◽  
...  

Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 980-987
Author(s):  
E Schlick ◽  
FW Ruscetti

We have investigated the mechanisms by which colony-stimulating factor (CSF)-inducing biological response modifiers (BRM) may have beneficial effects on tumor-bearing hosts undergoing anti-tumor therapy. First, we have documented that treatment of mice with the chemically defined BRM maleic anhydride divinyl ether copolymer (MVE-2), which induces CSF secretion by macrophages (M phi) and bone marrow cells (BMC), significantly increased growth and differentiation of normal myelopoietic cells and counteracted the myelosuppressive effects of cyclophosphamide (CY). Second, we established that MVE-2 may exert CSF- mediated antitumor effects on certain leukemic tumor cells. Serum from mice pretreated in vivo with MVE-2, which contained CSF, induced terminal differentiation of cloned tumor cells from the CSF responsive WEHI-3B D+ subline in vitro, but not from the WEHI-3B D- subline, which is unresponsive to CSF. In vivo experiments showed that treatment of mice bearing the WEHI-3B D+ tumor first with CY and three days later with the CSF inducer MVE-2, significantly increased their survival time and rendered 20% to 50% of the tumor-bearing mice disease free. No such effects were obtained in mice bearing the WEHI-3B D- tumor. Thus, the induction of CSF or other differentiation factors by some BRMs may result in therapeutic effects against certain leukemias based on at least two distinct mechanisms: In addition to their restorative effects on normal bone marrow functions, CSF-inducing BRMs may also prevent further leukemogenesis by induction of terminal differentiation of leukemic cells.


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.


Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 980-987 ◽  
Author(s):  
E Schlick ◽  
FW Ruscetti

Abstract We have investigated the mechanisms by which colony-stimulating factor (CSF)-inducing biological response modifiers (BRM) may have beneficial effects on tumor-bearing hosts undergoing anti-tumor therapy. First, we have documented that treatment of mice with the chemically defined BRM maleic anhydride divinyl ether copolymer (MVE-2), which induces CSF secretion by macrophages (M phi) and bone marrow cells (BMC), significantly increased growth and differentiation of normal myelopoietic cells and counteracted the myelosuppressive effects of cyclophosphamide (CY). Second, we established that MVE-2 may exert CSF- mediated antitumor effects on certain leukemic tumor cells. Serum from mice pretreated in vivo with MVE-2, which contained CSF, induced terminal differentiation of cloned tumor cells from the CSF responsive WEHI-3B D+ subline in vitro, but not from the WEHI-3B D- subline, which is unresponsive to CSF. In vivo experiments showed that treatment of mice bearing the WEHI-3B D+ tumor first with CY and three days later with the CSF inducer MVE-2, significantly increased their survival time and rendered 20% to 50% of the tumor-bearing mice disease free. No such effects were obtained in mice bearing the WEHI-3B D- tumor. Thus, the induction of CSF or other differentiation factors by some BRMs may result in therapeutic effects against certain leukemias based on at least two distinct mechanisms: In addition to their restorative effects on normal bone marrow functions, CSF-inducing BRMs may also prevent further leukemogenesis by induction of terminal differentiation of leukemic cells.


Nanomedicine ◽  
2019 ◽  
Vol 14 (18) ◽  
pp. 2461-2479
Author(s):  
Nayra M Kamel ◽  
Maged W Helmy ◽  
Magda W Samaha ◽  
Doaa Ragab ◽  
Ahmed O Elzoghby

Aim: Multicompartmental lipid–protein nanohybrids (MLPNs) were developed for combined delivery of the anticancer drugs tretinoin (TRE) and genistein (GEN) as synergistic therapy of lung cancer. Materials & methods: The GEN-loaded lipid core was first prepared and then coated with TRE-loaded zein shell via nanoprecipitation. Results: TRE/GEN-MLPNs demonstrated a size of 154.5 nm. In situ ion pair formation between anionic TRE and the cationic stearyl amine improved the drug encapsulation with enhanced stability of MLPNs. TRE/GEN-coloaded MLPNs were more cytotoxic against A549 cancer cells compared with combined free GEN/TRE. In vivo, lung cancer bearing mice treated with TRE/GEN-MLPNs displayed higher apoptotic caspase activation compared with mice-treated free combined GEN/TRE. Conclusion: TRE/GEN-MLPNs might serve as a promising parenteral nanovehicles for lung cancer therapy.


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