Co-drug delivery of regorafenib and cisplatin with amphiphilic copolymer nanoparticles: enhanced
            <i>in vivo</i>
            antitumor cancer therapy in nursing care

Zhou, Zhe

doi:10.1080/10717544.2020.1815897

Cited by 15 publications

(3 citation statements)

References 47 publications

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“…One of the essential properties of nanoparticles as carriers of chemo-radiation therapy for cancer is validated mainly by its selective action toward tumors without damaging healthy organs ( 49 ). Micrographs show histological characteristics that define colorectal adenocarcinomas in tumors of the subcutaneous xenograft model of HCT116 cells, including epithelial cells and pleomorphic cell elements, mitotic forms (red arrow), and atypical nuclei (black arrow; Figure 14 , upper panel).…”

Section: Resultsmentioning

confidence: 99%

Chemo-radiotherapy with 177Lu-PLGA(RGF)-CXCR4L for the targeted treatment of colorectal cancer

et al. 2023

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IntroductionMore than 1.9 million new cases of colorectal cancer and 935,000 deaths were estimated to have occurred worldwide in 2020. Therapies for metastatic colorectal cancer include cytotoxic chemotherapy and targeted therapies in multiple lines of treatment. Nevertheless, the optimal use of these agents has not yet been resolved. Regorafenib (RGF) is an Food and Drug Administration (FDA)-authorized multikinase inhibitor indicated for patients with metastatic colorectal cancer, non-responding to priority lines of chemotherapy and immunotherapy. Nanoparticles have been used in specific applications, such as site-specific drug delivery systems, cancer therapy, and clinical bioanalytical diagnostics. C-X-C Chemokine receptor type 4 (CXCR4) is the most widely-expressed chemokine receptor in more than 23 human cancer types, including colorectal cancer. This research aimed to synthesize and preclinically evaluate a targeted nanosystem for colorectal cancer chemo-radiotherapy using RGF encapsulated in Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles coated with a CXCR4 ligand (CXCR4L) and 177Lu as a therapeutic β-emitter.MethodsEmpty PLGA and PLGA(RGF) nanoparticles were prepared using the microfluidic method, followed by the DOTA and CXCR4L functionalization and nanoparticle radiolabeling with 177Lu. The final nanosystem gave a particle size of 280 nm with a polydispersity index of 0.347. In vitro and in vivo toxicity effects were assessed using the HCT116 colorectal cancer cell line.Results177Lu-PLGA(RGF)-CXCR4L nanoparticles decreased cell viability and proliferation by inhibiting Erk and Akt phosphorylation and promoting apoptosis. Moreover, in vivo administration of 177Lu-PLGA(RGF)-CXCR4L significantly reduced tumor growth in an HCT116 colorectal cancer xenograft model. The biokinetic profile showed hepatic and renal elimination.DiscussionData obtained in this research justify additional preclinical safety trials and the clinical evaluation of 177Lu-PLGA(RGF)-CXCR4L as a potential combined treatment of colorectal cancer.

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Section: Resultsmentioning

confidence: 99%

Chemo-radiotherapy with 177Lu-PLGA(RGF)-CXCR4L for the targeted treatment of colorectal cancer

et al. 2023

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Section: Discussionmentioning

confidence: 99%

“…Following the discovery of Regorafenib, some studies have performed on the combined effects of Regorafenib with other chemotherapeutic agents [ 42 , 43 ]. On the other hand, the overuse and the combination of several chemotherapeutic drugs is a potential factor in drug resistance development [ 42 ]. Hence, in the last decade, the use of phytochemicals along with chemotherapy drugs has been developed to counteract drug resistance mechanisms [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Combination of Quercetin or/and siRNA-loaded DDAB-mPEG-PCL hybrid nanoparticles reverse resistance to Regorafenib in colon cancer cells

Shahidi

Rostamizadeh

Fathi

et al. 2022

BMC Complement Med Ther

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Background Colorectal cancer (CRC) is the second leading cause of cancer death. Although Regorafenib showed survival benefits in patients with CRC, reports imply the recurrence of malignant phenotype resulting from chemotherapy. Evidence demonstrated that a5β1 integrin plays an important role in the Regorafenib treatment, which, may be led to resistance. In this study, the effects of /siRNA or/ and Quercetin loaded DDAB-mPEG-PCLnanoparticles could reverse this resistance phenotype in colon cancer cells in vitro. Methods Regorafenib-resistant Ls-180 colon cancer cell line was developed by long-term exposure to Regorafenib. Quercetin and Regorafenib were separately encapsulated into mPEG-PCL micelles through the nano-precipitation method and characterized by DLS. Optimized doses of Quercetin and Regorafenib were used for combination therapy of resistant cells followed cytotoxicity study using MTT. Gene expression levels of the β1 subunit of integrin were determined by the real-time method of RT-PCR. Results Developed Regorafenib resistant LS-180 showed to have Regorafenib IC50 of 38.96 ± 1.72 µM whereas IC50 in non-resistant cells were 8.51 ± 0.29 µM, which meaningful was lower statistically compared to that of a resistant one. The β1 mRNA level of whole α5β1 integrin was significantly higher in the resistant cells compared to those of non-resistant ones. Gene expression levels in each siRNA-loaded nanoparticle and Quercetin-loaded one were lower than that in mock experiments. Finally, when these two types of nanoparticles were used to treat resistant cells, gene expression decrease of integrin indicated a greater effect that could be capable of reverse resistancy. Conclusion Results of this study demonstrated another confirmation of involving integrins in cancer resistance following chemotherapy using Regorafenib. Also, it indicated how using siRNA targeting integrin could enhance the plant derivatives like Quercetin effects to reverse resistance in vitro.

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Platinum Drug‐Incorporating Polymeric Nanosystems for Precise Cancer Therapy

Liu

Wang

et al. 2023

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made great progress in the field of medicinal inorganic chemistry. [2] They have been extensively applied in various types of cancers such as bladder cancer, ovarian cancer, breast cancer, endometrial cancer, neck cancer, and lung cancer. [3] Generally, Pt-based anticancer drugs interact with gene nucleobases and cause DNA damage. For example, after cellular uptake, cisplatin will hydrolyze along with the dissociation of chloride ion, which is ascribed to relatively lower concentration of chloride ion in cytoplasm (4-10 mm) than that in blood (≈100 mm). The hydrolyzed cisplatin can further conjugate with N7 position of adenine (A) and guanine (G), distort the structure of DNA and inhibit G2/M transition of cell cycle, leading to cell apoptosis in the end. [4][5][6] However, Pt(II) analogue drugs face various side effects, such as vomiting, neurotoxicity, nephrotoxicity, ototoxity, and cardiotoxicity. [7] These severe side effects greatly limit their efficacy and have become huge obstacles for further clinical applications. Though great efforts have been devoted to improve the efficacy of Pt-based anticancer drugs. Up to now, there is no Pt(II)-based drug that fully solves the problems despite of years of research. [8,9] Meanwhile, drug resistance is another major challenge for Pt-based drugs. Further, the anticancer efficacy of these Pt(II)-based drugs is greatly compromised by the inactivation of intracellular coppertransporting proteins, such as glutathione (GSH) and metallothioneins (MT), through forming stable Pt(II)-S bond. Later, copper transporter ATP7A and ATP7B are involved in the efflux or translocation Pt(II)-S complex as well as multidrug resistance-associated protein MRP2. What's more, it is noteworthy that DNA damage caused by Pt lesions can be recovered by the nucleotide excision repair (NER) machinery, in which DNAadduct repair enzymes play the critical role, such as excision repair cross complementation 1. [10,11] To minimize side effects of Pt(II) drugs, Pt(IV) prodrug have drawn more and more attention for cancer therapy. [12][13][14][15][16] Compared to Pt(II) drugs, these Pt(IV) drugs have a six coordinate octahedral geometry with an inert d 6 electronic configuration. The two additional ligands can endow Pt(IV) prodrugs with additional lipophilicity, tumor targeting property, and enhanced cellular uptake. [17] After endocytosis, these Pt(IV) drugs can be reduced to active Pt(II) drugs by intracellular GSH, resulting in enhanced therapeutic efficacy and reduced side effects. [18] Ideally, Pt drugs should kill cancer cells exclusively without damaging the normal ones. However, the tumor selectivity of Platinum (Pt) drugs are widely used in clinic for cancer therapy, but their therapeutic outcomes are significantly compromised by severe side effects and acquired drug resistance. With the emerging immunotherapy and imaging-guided cancer therapy, precise delivery and release of Pt drugs have drawn great attention these days. The targeting delivery of Pt drugs can greatly increase the accumulation...

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Co-drug delivery of regorafenib and cisplatin with amphiphilic copolymer nanoparticles: enhanced in vivo antitumor cancer therapy in nursing care

Cited by 15 publications

References 47 publications

Chemo-radiotherapy with 177Lu-PLGA(RGF)-CXCR4L for the targeted treatment of colorectal cancer

Chemo-radiotherapy with 177Lu-PLGA(RGF)-CXCR4L for the targeted treatment of colorectal cancer

Combination of Quercetin or/and siRNA-loaded DDAB-mPEG-PCL hybrid nanoparticles reverse resistance to Regorafenib in colon cancer cells

Platinum Drug‐Incorporating Polymeric Nanosystems for Precise Cancer Therapy

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