Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer

Paredes, Karina Ovejero; Díaz-García, Diana; García-Almodóvar, Victoria; Chamizo, Laura Lozano; Marciello, Marzia; Díaz-Sánchez, Miguel; Prashar, Sanjiv; Gómez‐Ruiz, Santiago; Filice, Marco

doi:10.3390/cancers12010187

Cited by 60 publications

(31 citation statements)

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“…The hydrodynamic size of materials MSN-AP-FA25-Sn and MSU-2-AP-FA25-Sn were of 333.1 nm (polydispersity index (PDI) of 0.29) and 2293 nm (PDI of 0.27), respectively. The sizes were in the expected range [ 34 ] and showed higher sizes than those found for TEM measurements. This is due to the functionalization of the materials with the different moieties (FA and organotin(IV) compound).…”

Section: Resultsmentioning

confidence: 93%

“…Considering that most of the studied systems do not bear any potential targeting molecule to detect and potentiate the active and selective transport of the therapeutic species to the cancer cell line, an enhanced permeability and retention (EPR) effect was considered to be responsible for their slight selectivity towards cancer cell lines (in comparison with normal cell lines) [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Nevertheless, very recent reports have studied the possibility of including a folate fragment for a more effective targeting of cancer cells, which has been partially achieved both in vitro [ 33 ] and in vivo [ 34 ] when using organotin(IV)-functionalized mesoporous silica nanoparticles. Using this strategy of introducing folate fragments, an increase in the selectivity of functionalized-nanostructured silica systems has been achieved using a wide variety of organic approved drugs; however, the biological mechanism of action, including the receptor study of these systems, has still not been elucidated [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ].…”

Section: Introductionmentioning

confidence: 99%

“…As the number of reports of folate-containing metallodrug-functionalized mesoporous silica nanomaterials is very low and limited to the previous studies of our team with tin(IV) derivatives [ 33 , 34 ] and other therapeutic gold(III) compounds [ 48 ], a detailed study was proposed to determine some biological aspects related to the use of these kinds of fragments in cancer chemotherapy in vitro. In general, the folate receptor is a recognised biomarker for tumour cells, usually enabling improvement in cancer cell uptake and potential delivery of the drugs inside the cells [ 49 ].…”

Section: Introductionmentioning

confidence: 99%

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Role of Folic Acid in the Therapeutic Action of Nanostructured Porous Silica Functionalized with Organotin(IV) Compounds against Different Cancer Cell Lines

et al. 2020

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The synthesis, characterization and cytotoxic activity against different cancer cell lines of various mesoporous silica-based materials containing folate targeting moieties and a cytotoxic fragment based on a triphenyltin(IV) derivative have been studied. Two different mesoporous nanostructured silica systems have been used: firstly, micronic silica particles of the MSU-2 type and, secondly, mesoporous silica nanoparticles (MSNs) of about 80 nm. Both series of materials have been characterized by different methods, such as powder X-ray diffraction, X-ray fluorescence, absorption spectroscopy and microscopy. In addition, these systems have been tested against four different cancer cell lines, namely, OVCAR-3, DLD-1, A2780 and A431, in order to observe if the size of the silica-based systems and the quantity of incorporated folic acid influence their cytotoxic action. The results show that the materials are more active when the quantity of folic acid is higher, especially in those cells that overexpress folate receptors such as OVCAR-3 and DLD-1. In addition, the study of the potential modulation of the soluble folate receptor alpha (FOLR1) by treatment with the synthesized materials has been carried out using OVCAR-3, DLD-1, A2780 and A431 tumour cell lines. The results show that a relatively high concentration of folic acid functionalization of the nanostructured silica together with the incorporation of the cytotoxic tin fragment leads to an increase in the quantity of the soluble FOLR1 secreted by the tumour cells. In addition, the studies reported here show that this increase of the soluble FOLR1 occurs presumably by cutting the glycosyl-phosphatidylinositol anchor of membrane FR-α and by the release of intracellular FR-α. This study validates the potential use of a combination of mesoporous silica materials co-functionalized with folate targeting molecules and an organotin(IV) drug as a strategy for the therapeutic treatment of several cancer cells overexpressing folate receptors.

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Section: Resultsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of Folic Acid in the Therapeutic Action of Nanostructured Porous Silica Functionalized with Organotin(IV) Compounds against Different Cancer Cell Lines

et al. 2020

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“…Within this Special Issue, a diverse range of cancer nanomedicines have been discussed, including the more traditional organic-based systems, such as lipid [ 1 , 2 , 3 , 4 , 5 , 6 ], polymer [ 7 , 8 , 9 , 10 , 11 ] and cyclodextrin-based [ 12 ] particulates. Additionally, there are multiple studies from the growing area of inorganic systems, such as carbon nanomaterials (such as graphene oxide [ 13 , 14 ] and carbon nanotubes [ 15 ]) as well as other more established metallic nanomaterials, such as gold [ 16 , 17 ], iron oxide [ 18 , 19 ] and silica-based [ 20 , 21 ] systems. Interest into such inorganic systems has boomed over the last ten years, largely down to their multifunctional capabilities, in imaging [ 15 ], photothermal ability [ 22 , 23 ] or use in radiation enhancement [ 24 ].…”

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confidence: 99%

“…These platforms can be used for combined diagnostics and therapy, known as theranostics. The theranostic community is growing rapidly and in this issue a review of theranostics under development [ 25 ] as well a scientific paper [ 20 ] have been included.…”

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confidence: 99%

Cancer Nanomedicine

Hoskins

2020

Cancers

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Nanoparticle‐Mediated siRNA Delivery and Multifunctional Modification Strategies for Effective Cancer Therapy

Chen

Dong

Shi

2021

Adv Materials Technologies

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method clinically, however, it is accompanied by the inevitable side effects on normal tissues. [9] Similarly, other treatment methods have failed to achieve satisfactory treatment results in clinic. With the discovery of key oncogenic markers and pathways, gene therapy has become a novel class of pharmaceutical drugs and shown significant therapeutic advantages in fighting cancer. [10][11][12] Compared with chemotherapy, gene therapy has better selectivity and specificity for related genes.RNA interference (RNAi) is an important defense mechanism of eukaryotic cells, which inhibits the expression or transcription of specific genes by blocking their translation or transcription, so it is considered to be a revolutionary tool for mediating gene therapy. [13][14][15] Previous research has shown that RNAi can effectively modulating the expression of any gene involved in tumor initiation, growth, and metastasis formation. [16][17][18] MicroRNA (miRNA), small interfering RNA (siRNA), and short hairpin RNA (shRNA) are the major types of RNAi molecules, which can mediate RNAi and cause mRNA cleavage. [19] miRNA is an endogenous single-stranded RNA, which mainly acts on the 3'-untranslated region of target genes in the RNAi pathway. [20] While siRNA is a double-stranded RNA (dsRNA) which can be transfected into the human body and act on any part of mRNA. [21] shRNA can be cloned into an expression vector and express siRNA. [22] siRNA has powerful specific RNAi triggering activity, so it shows great potential in nucleic acid therapy. [23] siRNA is a 20-25 base pair nucleic acid fragment that can degrade messenger RNA (mRNA) in the cytoplasm and interfere with the expression of specific genes. [24][25][26] The mechanism of siRNA-mediated RNAi action is shown in Figure 1. siRNA is synthesized and delivered into the cytoplasm, or generated by the endogenous Dicer-mediated dsRNA cleavage, then it can be incorporated into the RNA-induced silencing complex (RISC, a multi-protein complex). Then the sense strand (nonguiding strand) is cleaved by the Argonaute 2 (AGO2, an endonuclease of the RISC), while the antisense strand guides RISC toward the target mRNA with a complementary sequence, which is further cleaved by AGO2 into mRNA fragments. Subsequently, the mRNA fragments are degraded by cellular exonuclease. In addition, the antisense strand-RISC complex is capable of being recycled, so effectively preventing the translation of target mRNA into proteins.RNA interference (RNAi), which can inhibit the expression or transcription of specific genes, is considered to be a revolutionary tool for mediating gene therapy. Small interfering RNA (siRNA) is an important therapeutic agent for RNAi. However, the clinical application of siRNA-based gene silencing is still limited due to the easy degradation of siRNA during the circulation in the body and the difficulty in delivering siRNA to desired tissues and cells. The rapid development of nanotechnology provides new ideas for siRNA delivery and a large variety of nanocarriers have been d...

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Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer

Cited by 60 publications

References 76 publications

Role of Folic Acid in the Therapeutic Action of Nanostructured Porous Silica Functionalized with Organotin(IV) Compounds against Different Cancer Cell Lines

Role of Folic Acid in the Therapeutic Action of Nanostructured Porous Silica Functionalized with Organotin(IV) Compounds against Different Cancer Cell Lines

Cancer Nanomedicine

Nanoparticle‐Mediated siRNA Delivery and Multifunctional Modification Strategies for Effective Cancer Therapy

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