Enhancing the anticancer effect of paclitaxel by using polymeric nanoparticles decorated with colorectal cancer targeting CPKSNNGVC-peptide

Bortezomib (BTZ) as a specific proteasome inhibitor is used to inhibit proliferation and migration of tumor cell in variety of cancers. Targeted delivery of this drug not only would minimize its unwanted side effects but also might improve its efficacy. This purpose could be gotten through different pathways but using efficient carriers may be the best one without using any additional ingredients/ materials. Some polymer based nanoparticles with specific functional groups have the ability to interact with boronic acid moiety in BTZ. This reaction might play an important role not only in cancer targeting therapy but also in loading and release properties of this drug. Novel modification such as making multifunctional or pH-sensitive nanocarriers, may also improve anticancer effect of BTZ. This review might have remarkable effect on researchers’ consideration about other possible interactions between BTZ and polymeric nanocarriers that might have great effect on its remedy pathway. It has the ability to brought bright ideas to their minds for novel amendments about other drugs and delivery systems.

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Biochemical assessment of the neurotoxicity of gold nanoparticles functionalized with colorectal cancer-targeting peptides in a rat model

Human & Experimental Toxicology ◽

10.1177/09603271211017611 ◽

2021 ◽

pp. 096032712110176

Author(s):

MC Pereira ◽

OB Adewale ◽

S Roux ◽

L Cairncross ◽

H Davids

Keyword(s):

Oxidative Stress ◽

Colorectal Cancer ◽

Brain Tissue ◽

Tumour Necrosis ◽

Cancer Targeting ◽

Tumour Necrosis Factor Α ◽

Peptide Conjugates ◽

Factor Α ◽

Apoptotic Effects ◽

Necrosis Factor

The application of gold nanoparticle-peptide conjugates as theranostic agents for colorectal cancer shows much promise. This study aimed at determining the neurotoxic impact of 14 nm gold nanoparticles (AuNPs) functionalized with colorectal cancer-targeting peptides (namely p.C, p.L or p.14) in a rat model. Brain tissue samples, obtained from Wistar rats that received a single injection of citrate-capped AuNPs, polyethylene glycol-coated (PEG) AuNPs, p.C-PEG-AuNPs, p.L-PEG-AuNPs or p.14-PEG-AuNPs, and sacrificed after 2- and 12-weeks, respectively, were analysed. Inflammation marker (tumour necrosis factor-α, interleukin-6, interleukin-1β), oxidative stress (superoxide dismutase, catalase, glutathione peroxidase) and apoptotic biomarker (cytochrome c, caspase-3) levels were measured. Gold nanoparticle-treated groups sacrificed after 2-weeks did not exhibit any significant inflammatory, oxidative stress or apoptotic effects in brain tissue compared to the untreated control group. In brain tissue from rats that were exposed to citrate-capped AuNPs for 12-weeks, tumour necrosis factor-α and interleukin-6 levels were significantly increased compared to the untreated control. Exposure to PEG-AuNP, p.C-PEG-AuNP, p.L-PEG-AuNP and p.14-PEG-AuNP did not elicit significant toxic effects compared to the control after 12-weeks, as evidenced by the absence of inflammatory, oxidative stress and apoptotic effects in brain tissue. We thus report on the safety of PEG-coated AuNP-peptide conjugates for potential application in the diagnosis of colorectal cancer; however, exposure to citrate-capped AuNPs could induce delayed neuro-inflammation, and as such, warrants further investigation.

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Sulfonamide-Functionalized Polymeric Nanoparticles For Enhanced In Vivo Colorectal Cancer Therapy

Current Drug Delivery ◽

10.2174/1567201818666210729110127 ◽

2021 ◽

Vol 18 ◽

Author(s):

Pedro Pires Goulart Guimarães ◽

Celso Tarso Rodrigues Viana ◽

Luciana Pereira ◽

Savio Morato Lacerda Gontijo ◽

Paula Peixoto Campos ◽

...

Keyword(s):

Colorectal Cancer ◽

Polymeric Nanoparticles ◽

Acquired Resistance ◽

Lung Mass ◽

Cancer Model ◽

Liver Mass ◽

Therapeutic Delivery ◽

Promising Strategy ◽

Common Cancer

Background: Colorectal cancer (CRC) is the third most common cancer in the world. 5-Fluorouracil (5-FU) is a conventional and most effective drug used in the clinic for the treatment of CRC. However, the clinical use of 5-FU is limited due to the acquired resistance and systemic toxicity, such as hepatotoxicity and gastrointesti-nal toxicity. Objective: Recent advances in nanomedicine are being exploited to develop nanoparticle platforms to overcome resistance and therapeutic delivery of active molecules. Here, we develop 5-FU loaded sulfadiazine-poly(lactide-co-glycolide) nanoparticles (SUL-PLGA NPs) to be applied in the colorectal cancer model. Methods: We assessed the in vivo efficacy of the SUL-PLGA NPs to enhance the antitumor effect of 5-FU. Results: In vivo treatment with 5-FU-SUL-PLGA NPs significantly reduced tumor growth in a colon cancer xen-ograft model compared to free 5-FU and 5-FU loaded non-targeted NPs. Treatment with 5-FU-SUL-PLGA NPs also increased blood vessel diameters within tumors, which could act in conjunction to enhance antitumor effi-cacy. In addition, 5-FU-SUL-PLGA NPs significantly reduced liver mass and lung mass, which are the most common metastasis sites of CRC, and decreased liver hepatotoxicity compared to free 5-FU drug and 5-FU loaded non-targeted NPs. Conclusion: Our findings suggest that the use of 5-FU-SUL-PLGA NPs is a promising strategy to enhance 5-FU efficacy against CRC.

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Serum Starvation Sensitizes Anticancer Effect of Anemarrhena asphodeloides via p38/JNK-Induced Cell Cycle Arrest and Apoptosis in Colorectal Cancer Cells

The American Journal of Chinese Medicine ◽

10.1142/s0192415x21500488 ◽

2021 ◽

pp. 1-16

Author(s):

Kon-Young Ji ◽

Ki Mo Kim ◽

Yun Hee Kim ◽

Ki-Shuk Shim ◽

Joo Young Lee ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Cycle ◽

Colon Cancer ◽

Cancer Cells ◽

Serum Starvation ◽

Anticancer Effect ◽

Cycle Arrest ◽

Colorectal Cancer Cells ◽

Anemarrhena Asphodeloides ◽

Hct116 Cells

The molecular mechanism underlying the anticancer effects of Anemarrhena asphodeloides (A. asphodeloides) on colon cancer is unknown. This is the first study evaluating the anticancer effect of A. asphodeloides extract (AA-Ex) in serum-starved colorectal cancer cells. Changes in cell proliferation and morphology in serum-starved MC38 and HCT116 colorectal cancer cells were investigated using MTS assay. Cell cycle and apoptosis were investigated using flow cytometry, and cell cycle regulator expression was determined using qRT-PCR. Apoptosis regulator protein levels and mitogen-activated protein kinase (MAPK) phosphorylation were assessed using western blotting. AA-Ex sensitively suppressed proliferation of serum-starved colorectal cancer cells, with MC38 and HCT116 cells showing greater changes in proliferation after treatment with AA-Ex under serum starvation than HaCaT and RAW 264.7 cells. AA-Ex inhibited cell cycle progression in serum-starved MC38 and HCT116 cells and increased the expression of cell cycle inhibitors (p53, p21, and p27). Furthermore, AA-Ex induced apoptosis in serum-starved MC38 and HCT116 cells. Consistently, AA-Ex suppressed the expression of the anti-apoptotic molecule Bcl-2 and upregulated pro-apoptotic molecules (cytochrome c, cleaved caspase-9, cleaved caspase-3, and cleaved-PARP) in serum-starved cells. AA-Ex treatment under serum starvation decreased AKT and ERK1/2 phosphorylation in the cell survival signaling pathway but increased p38 and JNK phosphorylation. Furthermore, AA-Ex treatment with serum starvation increased the levels of the transcription factors of the p38 and JNK pathway. Serum starvation sensitizes colorectal cancer cells to the anticancer effect of A. asphodeloidesvia p38/JNK-induced cell cycle arrest and apoptosis. Hence, AA-Ex possesses therapeutic potential for colon cancer treatment.

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