Transdermal delivery of small interfering RNAs with topically applied mesoporous silica nanoparticles for facile skin cancer treatment

Lio, Daniel Chin Shiuan; Liu, Chenghao; Oo, Myo Myo Swe; Wiraja, Christian; Teo, Melissa Hui Yen; Zheng, Mengjia; Chew, Sharon Wan Ting; Wang, Xiaomeng; Xu, Chen

doi:10.1039/c9nr06303j

Cited by 50 publications

(35 citation statements)

References 49 publications

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“…In the last decade, different cationic polymers, such as polyethylenimine (PEI) [ 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ], poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) [ 74 , 75 ], chitosan derivatives [ 76 ], poly l -arginine [ 77 ] or poly l -lysine (PLL) [ 78 ], have been reported as coatings for silica nanoparticles in gene delivery systems, either through simple electrostatic interactions with the surface silanol groups, through covalent silane coupling with trialkoxysilanes, or by amidation reactions of amine-containing polymers with carboxylated NPs [ 20 ]. Table 3 summarizes a variety of different polymer-modified silica-based gene delivery formulations recently reported in literature.…”

Section: Hybrid Silica Nanoparticlesmentioning

confidence: 99%

“…PLL polymers have also been commonly used for gene delivery purposes due to their low immunogenicity and great DNA loading ability [ 11 , 90 ]. Lio and co-workers recently developed a topical formulation based on PLL-coated MSNs for the transdermal delivery of siRNA [ 78 ]. In vivo biodistribution studies in tumor-bearing mice compared the topical application with intratumor and intravenous administration of the Cy5-labeled nanosystem, as presented in Figure 13 a.…”

Section: Hybrid Silica Nanoparticlesmentioning

confidence: 99%

“…Additionally, the system enabled the topical delivery of siRNA targeting transforming growth factor beta receptor 1 (TGFβR-1), which is overexpressed in about 80% of patients with squamous cell carcinoma (SCC) of the skin, its suppression presenting anti-tumor effects. An 18-day topical treatment in a mouse tumor xenograft model demonstrated the successful gene regulation effect of the system, resulting in a 2-fold abolishment of TGFβR-1 expression in tumor tissue and approximately 2.5-fold tumor growth inhibition, in comparison to scrambled siRNA or the PBS-treated control [ 78 ]. Möller’s work describes a different gene delivery system that comprises artificial amino acids to form a modularly designed block copolymer, in combination with oleic acid blocks, to act as a capping and endosomal release agent of MSNs [ 81 ].…”

Section: Hybrid Silica Nanoparticlesmentioning

confidence: 99%

“… Biodistribution studies of Cy5-marked PLL-coated MSNs: ( a ) Illustration of the administration routes tested for in vivo studies in squamous cell carcinoma (SCC) mice xenograft model; ( b ) Representative IVIS images of mice treated with Cy5-marked PLL-MSNs; ( c ) Fluorescence quantification of IVIS images; ( d ) Intensity of fluorescence of isolated tumor and major organs after 18-day treatment. Adapted from [ 78 ], with permission from Royal Society of Chemistry. …”

Section: Figurementioning

confidence: 99%

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Silica-Based Gene Delivery Systems: From Design to Therapeutic Applications

2020

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Advances in gene therapy have been foreshadowing its potential for the treatment of a vast range of diseases involving genetic malfunctioning. However, its therapeutic efficiency and successful outcome are highly dependent on the development of the ideal gene delivery system. On that matter, silica-based vectors have diverted some attention from viral and other types of non-viral vectors due to their increased safety, easily modifiable structure and surface, high stability, and cost-effectiveness. The versatility of silane chemistry and the combination of silica with other materials, such as polymers, lipids, or inorganic particles, has resulted in the development of carriers with great loading capacities, ability to effectively protect and bind genetic material, targeted delivery, and stimuli-responsive release of cargos. Promising results have been obtained both in vitro and in vivo using these nanosystems as multifunctional platforms in different potential therapeutic areas, such as cancer or brain therapies, sometimes combined with imaging functions. Herein, the current advances in silica-based systems designed for gene therapy are reviewed, including their main properties, fabrication methods, surface modifications, and potential therapeutic applications.

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Section: Hybrid Silica Nanoparticlesmentioning

confidence: 99%

Section: Hybrid Silica Nanoparticlesmentioning

confidence: 99%

Section: Hybrid Silica Nanoparticlesmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Silica-Based Gene Delivery Systems: From Design to Therapeutic Applications

2020

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“…Moreover, Huang X. and collaborators assessed the effect of mesoporous silica nanoparticles on tumour proliferation while using a model of nude mice xenografted with A375 cells [51]. Additionally, the following reasons led us to the selection of this cell line: (i) both superparamagnetic iron and silica nanoparticles proved to be reliable nanoplatforms for the detection and treatment of different cancers, including melanoma [40,[52][53][54][55] and (ii) A375 melanoma cell line presents the characteristics of the human genitor and possess B-RAF and CDKN2 mutations, which are typical of cutaneous melanoma, representing an eligible candidate for the development of in vivo models [56].…”

Section: Introductionmentioning

confidence: 99%

SiO2-PVA-Fe(acac)3 Hybrid Based Superparamagnetic Nanocomposites for Nanomedicine: Morpho-textural Evaluation and In Vitro Cytotoxicity Assay

et al. 2020

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A facile sol-gel route has been applied to synthesize hybrid silica-PVA-iron oxide nanocomposite materials. A step-by-step calcination (processing temperatures up to 400 °C) was applied in order to oxidize the organics together with the iron precursor. Transmission electron microscopy, X-ray diffraction, small angle neutron scattering, and nitrogen porosimetry were used to determine the temperature-induced morpho-textural modifications. In vitro cytotoxicity assay was conducted by monitoring the cell viability by the means of MTT assay to qualify the materials as MRI contrast agents or as drug carriers. Two cell lines were considered: the HaCaT (human keratinocyte cell line) and the A375 tumour cell line of human melanoma. Five concentrations of 10 µg/mL, 30 µg/mL, 50 µg/mL, 100 µg/mL, and 200 µg/mL were tested, while using DMSO (dimethylsulfoxid) and PBS (phosphate saline buffer) as solvents. The HaCaT and A375 cell lines were exposed to the prepared agent suspensions for 24 h. In the case of DMSO (dimethyl sulfoxide) suspensions, the effect on human keratinocytes migration and proliferation were also evaluated. The results indicate that only the concentrations of 100 μg/mL and 200 μg/mL of the nanocomposite in DMSO induced a slight decrease in the HaCaT cell viability. The PBS based in vitro assay showed that the nanocomposite did not present toxicity on the HaCaT cells, even at high doses (200 μg/mL agent).

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Hyperglycemia Targeting Nanomotors for Accelerated Healing of Diabetic Wounds by Efficient Microenvironment Remodeling

Lin,

Lian,

et al. 2024

Adv Funct Materials

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Multifunctional nanoagents are robust to remodel environments for managing chronic diabetic wounds. However, their delivery primarily relies on Brownian motion and randomly enhanced diffusion. Here, taking advantage of wound heterogeneity, such as the uneven distribution of glucose, hyperglycemia targeting nanomotors are proposed. They are capable of efficiently targeting hyperglycemic interfaces in diabetic wounds for significantly accelerating their healing by employing endogenous glucose‐activated cascade reactions and responding to local glucose gradients. Compared to previous counterparts, they show a four‐fold enhancement in effective coverage within 60 s and a multiplied accumulation at hyperglycemic interfaces, facilitating deep penetration. Correspondingly, the downregulation of glucose levels is apparently enhanced, while pH‐lowering and oxygen‐supplying are both improved. In comparison to the counterparts delivered by passive diffusion and randomly enhanced diffusion, the hyperglycemia targeting nanomotor‐based spray accelerates the wound healing upon diabetic mice by approximately 30% and 23%, resulting from the restricted inflammatory response, effective reactive oxygen species (ROS) scavenging and elevated vascular endothelial growth factor levels (VEGF). This study presents a generally efficient approach to facilitating the targeted delivery of nanoagents for the effective management of diabetic wounds by utilizing wound heterogeneity, which can be extended to other therapeutic systems.

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Transdermal delivery of small interfering RNAs with topically applied mesoporous silica nanoparticles for facile skin cancer treatment

Abstract: Development of siRNA-loaded mesoporous Silica nanoparticles coated with poly-l-lysine for enhanced transdermal drug delivery in skin cancer treatment.

Cited by 50 publications

References 49 publications

Silica-Based Gene Delivery Systems: From Design to Therapeutic Applications

Silica-Based Gene Delivery Systems: From Design to Therapeutic Applications

SiO2-PVA-Fe(acac)3 Hybrid Based Superparamagnetic Nanocomposites for Nanomedicine: Morpho-textural Evaluation and In Vitro Cytotoxicity Assay

Hyperglycemia Targeting Nanomotors for Accelerated Healing of Diabetic Wounds by Efficient Microenvironment Remodeling

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