Nanoparticles Loaded with Platinum Drugs for Colorectal Cancer Therapy

Buyana, Buhle; Naki, Tobeka; Alven, Sibusiso; Aderibigbe, Blessing Atim

doi:10.3390/ijms231911261

Cited by 19 publications

(6 citation statements)

References 174 publications

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“…Although modifying the structure of the antitumor drugs is a valuable approach for the discovery of new anticancer drugs, an additional strategy to expand the pharmacological properties of compounds to improve the pharmacological effects—concomitantly leading to lower side effects—is the encapsulation of anticancer-active entities into biocompatible nanoparticles. Nowadays, several successful examples of drug encapsulation and delivery have been reported in the scientific literature [ 97 , 98 , 99 , 100 , 101 ]. On this basis, we also performed a pilot study based on the encapsulation of PTG in the core of PLGA-PEG nanoparticles, thus forming the aforementioned drug-delivery system.…”

Section: Resultsmentioning

confidence: 99%

Oxaliplatin(IV) Prodrugs Functionalized with Gemcitabine and Capecitabine Induce Blockage of Colorectal Cancer Cell Growth—An Investigation of the Activation Mechanism and Their Nanoformulation

Marotta,

Cirri,

Kanavos

et al. 2024

Pharmaceutics

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The use of platinum-based anticancer drugs, such as cisplatin, oxaliplatin, and carboplatin, is a common frontline option in cancer management, but they have debilitating side effects and can lead to drug resistance. Combination therapy with other chemotherapeutic agents, such as capecitabine and gemcitabine, has been explored. One approach to overcome these limitations is the modification of traditional Pt(II) drugs to obtain new molecules with an improved pharmacological profile, such as Pt(IV) prodrugs. The design, synthesis, and characterization of two novel Pt(IV) prodrugs based on oxaliplatin bearing the anticancer drugs gemcitabine or capecitabine in the axial positions have been reported. These complexes were able to dissociate into their constituents to promote cell death and induce apoptosis and cell cycle blockade in a representative colorectal cancer cell model. Specifically, the complex bearing gemcitabine resulted in being the most active on the HCT116 colorectal cancer cell line with an IC50 value of 0.49 ± 0.04. A pilot study on the encapsulation of these complexes in biocompatible PLGA-PEG nanoparticles is also included to confirm the retention of the pharmacological properties and cellular drug uptake, opening up to the possible delivery of the studied complexes through their nanoformulation.

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Section: Resultsmentioning

confidence: 99%

Oxaliplatin(IV) Prodrugs Functionalized with Gemcitabine and Capecitabine Induce Blockage of Colorectal Cancer Cell Growth—An Investigation of the Activation Mechanism and Their Nanoformulation

Marotta,

Cirri,

Kanavos

et al. 2024

Pharmaceutics

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“…CRC cells have also developed some drug resistance to platinum agents, such as the inhibition of drug accumulation in tumor cells, as well as the acquisition of EMT. A large number of studies on drug resistance have found that exosomes loaded with miR-128-3p ( 156 ) and the application of nanoparticles ( 157 ) can re-sensitize CRC cells to platinum drugs in vivo .…”

Section: Exploration Of Neddylation As a Potential Molecularly Target...mentioning

confidence: 99%

Advancements in colorectal cancer research: Unveiling the cellular and molecular mechanisms of neddylation (Review)

Wang,

Li,

et al. 2024

Int J Oncol

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Neddylation, akin to ubiquitination, represents a post-translational modification of proteins wherein neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) is modified on the substrate protein through a series of reactions. Neddylation plays a pivotal role in the growth and proliferation of animal cells. In colorectal cancer (CRC), it predominantly contributes to the proliferation, metastasis and survival of tumor cells, decreasing overall patient survival. The strategic manipulation of the NEDD8-mediated neddylation pathway holds immense therapeutic promise in terms of the potential to modulate the growth of tumors by regulating diverse biological responses within cancer cells, such as DNA damage response and apoptosis, among others. MLN4924 is an inhibitor of NEDD8, and its combined use with platinum drugs and irinotecan, as well as cycle inhibitors and NEDD activating enzyme inhibitors screened by drug repurposing, has been found to exert promising antitumor effects. The present review summarizes the recent progress made in the understanding of the role of NEDD8 in the advancement of CRC, suggesting that NEDD8 is a promising anti-CRC target.

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“…With increasing cancer incidence and mortality, cancer has become a leading cause of death and poses a serious threat to the health and lives of people worldwide, making it a major global public health issue. Colorectal cancer exhibits high tumor heterogeneity and treatment typically involves a combination of surgery and chemotherapy based on disease grade, stage, and other characteristics 5 , 6 . With improvements in therapies and regimens, the 5-year survival rate of colorectal cancer patients has significantly improved to 65% 7 , 8 .…”

Section: Introductionmentioning

confidence: 99%

ASB6 as an Independent Prognostic Biomarker for Colorectal Cancer Progression Involves Lymphatic Invasion and Immune Infiltration

Hu,

Chen,

Zhou

et al. 2024

J. Cancer

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Background: ASB6, an E3 ubiquitin ligase, mediates the proteasomal degradation of its substrate proteins via the ubiquitin-proteasome pathway. ASB6 has been reported to play significant roles in several biological processes, including tumor stemness and endoplasmic reticulum stress. However, the underlying role and mechanism of ASB6 in colorectal cancer, particularly its association with immune infiltration levels and its prognostic significance, remain to be fully elucidated. Methods: We identified key prognostic genes in CRC patients through LASSO-penalized Cox regression, Univariate and Multivariate Cox regression analyses. Subsequently, we comprehensively analyzed the prognostic value of hub genes and constructed a prognostic nomogram. Finally, we identified ASB6 interacting proteins through immunoprecipitation-mass spectrometry (IP-MS) and constructed protein-protein interaction (PPI) networks and performed pathway enrichment analysis to explore the potential mechanisms of ASB6. Meanwhile, we evaluated the functions of ASB6 in CRC cells through in vitro cell experiments. Results: We identified ASB6 as a hub gene in CRC. ASB6 was highly expressed in CRC, and patients with high ASB6 expression had worse Disease-Free Interval (DFI), Disease-Specific Survival (DSS), Overall Survival (OS), and Progression-Free Interval (PFI). Correlation analysis showed that ASB6 expression were positively correlated with lymph node invasion and distal metastasis. Overexpression of ASB6 enhanced the migration ability of CRC cells. Multivariate Cox regression analysis revealed that ASB6 was an independent prognostic factor for OS and DSS in CRC. The nomogram model constructed based on multivariate analysis results had good predictive effects, with C-indexes of 0.811 and 0.934 for OS and DSS, respectively. Furthermore, analysis of immune infiltration levels showed that ASB6 expression were positively correlated with M2-type macrophage infiltration levels in CRC, and patients with high levels of both ASB6 and M2-type macrophages had a worse prognosis. Furthermore, pathway enrichment analysis of ASB6 interacting proteins identified by IP-MS suggested that ASB6 may play a crucial role through the response to unfolded protein pathway and protein processing in the endoplasmic reticulum pathway. Conclusions: ASB6 is significantly upregulated in CRC tissues and is a risk factor for prognosis in CRC patients. ASB6 enhances the migration ability of CRC cells. Therefore, ASB6 may be an independent prognostic biomarker and potential therapeutic target for CRC patients.

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Nanoparticles Loaded with Platinum Drugs for Colorectal Cancer Therapy

Cited by 19 publications

References 174 publications

Oxaliplatin(IV) Prodrugs Functionalized with Gemcitabine and Capecitabine Induce Blockage of Colorectal Cancer Cell Growth—An Investigation of the Activation Mechanism and Their Nanoformulation

Oxaliplatin(IV) Prodrugs Functionalized with Gemcitabine and Capecitabine Induce Blockage of Colorectal Cancer Cell Growth—An Investigation of the Activation Mechanism and Their Nanoformulation

Advancements in colorectal cancer research: Unveiling the cellular and molecular mechanisms of neddylation (Review)

ASB6 as an Independent Prognostic Biomarker for Colorectal Cancer Progression Involves Lymphatic Invasion and Immune Infiltration

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