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Polymer and polyplex preparation. Notes: (A) Synthesis of FA-PEG-SS-PEI polymer; (B) formation of FA-PEG-SS-PEI-SPION/siRNA polyplex. Abbreviations: FA, folic acid; PEG, polyethylene glycol; SS, disulfide; PEI, polyethylenimine; SPION, superparamagnetic iron oxide nanoparticle; DMAP, dimethylaminopyridine; NHS, N-hydroxysuccinimide; DCC, dicyclohexylcarbodiimide.
Source publication
Programmed death ligand-1 (PD-L1), which is highly expressed in gastric cancers, interacts with programmed death-1 (PD-1) on T cells and is involved in T-cell immune resistance. To increase the therapeutic safety and accuracy of PD-1/PD-L1 blockade, RNA interference through targeted gene delivery was performed in our study. We developed folic acid...
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We previously reported the utility of 6-O-α-(4-O-α-d-glucuronyl)-d-glucosyl-β-cyclodextrin (GUG-β-CyD) conjugates with polyamidoamine dendrimer [GUG-β-CDE (generation 3; G3)] as siRNA carriers. In this study, to prepare GUG-β-CDE (G3) possessing a targeting ability to tumor cells overexpressing folate receptor-α (FR-α), we newly synthesized folate-...
Citations
... Luo et al have focused on the treatment of gastric cancers having high expression of PD-L1 [109]. In this work, initially complex molecules made of folic acid (FA)-PEG-disulfide-PEI are formed. ...
RNA interference (RNAi) is one of the emerging methodologies utilized in the treatment of a wide variety of diseases including cancer. This method specifically uses therapeutic RNAs (TpRNAs) like small interfering RNAs (siRNAs) to regulate/silence the cancer-linked genes, thereby minimizing distinct activities of cancer cells and aiding in their apoptosis. But, many complications arise during the transport/delivery of these TpRNAs that include poor systemic circulation, instability/degradation inside the body environment, no targeting capacity and also low cellular internalization. These difficulties can be overcome by using nanocarriers to deliver the TpRNAs inside the cancer cells. The following are the various categories of nanocarriers - viral vectors (e.g., lentivirus and adenovirus) and non-viral nanocarriers (self-assembling nanocarriers and inorganic nanocarriers). Viral vectors suffer from few disadvantages like high immunogenicity as compared to the non-viral nanocarriers. Among non-viral nanocarriers, inorganic nanocarriers gained significant attention as their inherent properties (like magnetic properties) can aid in effective cellular delivery of the TpRNAs. Most of the prior reports have discussed about the delivery of TpRNAs through self-assembling nanocarriers; however very few have reviewed about their delivery using the inorganic nanoparticles. Therefore, in this review, we have mainly discussed the delivery of TpRNAs – i.e., siRNA, especially programmed death ligand-1 (PD-L1), survivin, B-cell lymphoma-2 (Bcl-2), vascular endothelial growth factor (VEGF) and other siRNAs using the inorganic nanoparticles – mainly magnetic, metal and silica nanoparticles. Moreover, we have discussed about the combined delivery of these TpRNAs along with chemotherapeutic drugs (mainly doxorubicin) and in vitro and in vivo therapeutic effectiveness.
... The positive rates for CEA and CA19-9 are in the range of 21-30%. The upper gastrointestinal endoscopy is considered for diagnosis of gastric cancer; however, its clinical application is limited due to its invasive nature and high expense [45][46][47][48][49]. Therefore, novel methods for the diagnosis of gastric cancer should be performed such as the application of nanomaterials with a theranostic capacity [50][51][52]. ...
... Folic acid, a low molecular weight biomolecule, is used as the targeting agent for stable and poor immunogenic properties [26]. A number of folic acid conjugated iron oxide nanoparticles have been reported to show better compatibility and targeting ability as well as enhanced drug accumulation in cancer cells [27][28][29][30][31][32]. Moreover, the conjugation of folic acid in luminescent inorganic nanoparticles also do not affect the luminescence of the nanoparticles and the folic acid conjugated nanoparticles exhibit high cell viability too [33]. ...
Silica-coated magnetic-luminescent nanocomposites, obtained from Mn0.8Fe2.2O4 and near-white emitting GdVO4:Dy³⁺, reported in this work for possible application in combined imaging and magnetic fluid hyperthermia. Folic acid functionalization of the nanocomposite was further achieved for enhanced tumor affinity since folate receptors are overexpressed in cancer tissues. The nanocomposite showed the cubic-tetragonal biphasic structure corresponding to the cubic Fe3O4 and tetragonal GdVO4 phases. The compositions and surface modifications were confirmed by infrared spectroscopy. The formation of agglomerated nanoparticle was observed from the transmission electron microscopy comprising of particles in the 20-nm size range. Brilliant near white emission can be seen from the nanocomposites upon excitation at 287 nm. The induction heating analysis was performed at the alternating magnetic field strengths of 2.15 × 10⁶ kAm⁻¹ s⁻¹, 3.05 × 10⁶ kAm⁻¹ s⁻¹, and 4.58 × 10⁶ kAm⁻¹ s⁻¹. The MTT assay revealed that the nanocomposite exhibits 50% cell viability towards MDA-231 breast cancer cell line. Thus, these magnetic-luminescent nanocomposites will have potential applications for magnetic fluid hyperthermia and optical imaging.
... The FA-PEG-PEI polymers successfully delivered si-PD-L1, with lower off-target toxicity and considerable cellular uptake. In addition, this regime resulted in PD-L1 downregulation in both mRNA and protein levels, further elevating the cytokine release of cocultured T cells [107]. ...
Immune checkpoint (ICP) molecules expressed on tumor cells can suppress immune responses against tumors. ICP therapy promotes anti-tumor immune responses by targeting inhibitory and stimulatory pathways of immune cells like T cells and dendritic cells (DC). The investigation into the combination therapies through novel immune checkpoint inhibitors (ICIs) has been limited due to immune-related adverse events (irAEs), low response rate, and lack of optimal strategy for combinatorial cancer immunotherapy (IMT). Nanoparticles (NPs) have emerged as powerful tools to promote multidisciplinary cooperation. The feasibility and efficacy of targeted delivery of ICIs using NPs overcome the primary barrier, improve therapeutic efficacy, and provide a rationale for more clinical investigations. Likewise, NPs can conjugate or encapsulate ICIs, including antibodies, RNAs, and small molecule inhibitors. Therefore, combining the drug delivery system (DDS) with ICP therapy could provide a profitable immunotherapeutic strategy for cancer treatment. This article reviews the significant NPs with controlled DDS using current data from clinical and pre-clinical trials on mono- and combination IMT to overcome ICP therapeutic limitations.
Graphical Abstract
... A bioengineered nanoparticle using SPIONs and siRNA-targeting PD-L1 for theranostics in gastric agents found improved MRI contrast, among other benefits. The MR images showed increased T2-weighted contrast, making it easier to visualize and therefore monitor cancer noninvasively [68]. Superparamagnetic iron oxide nanoparticles (SPIONs) possess improved magnetization properties, as well as biocompatibility and stability in aqueous solutions. ...
The targeted delivery of cancer immunotherapies has increased noticeably in recent years. Recent advancements in immunotherapy, particularly in blocking the immune checkpoints (ICs) axis, have shown favorable treatment outcomes for multiple types of cancer including melanoma and non-small-cell lung cancer (NSLC). Engineered micromachines, including microparticles, and nanoplatforms (organic and inorganic), functionalized with immune agonists can effectively deliver immune-targeting molecules to solid tumors. This review focuses on the nanomaterial-based strategies that have shown promise in identifying and targeting various immunological markers in the tumor microenvironment (TME) for cancer diagnosis and therapy. Nanomaterials-based cancer immunotherapy has improved treatment outcomes by triggering an immune response in the TME. Evaluating the expression levels of ICs in the TME also could potentially aid in diagnosing patients who would respond to IC blockade therapy. Detecting immunological checkpoints in the TME using noninvasive imaging systems via tailored nanosensors improves the identification of patient outcomes in immuno-oncology (IO). To enhance patient-specific analysis, lab-on-chip (LOC) technology is a rapid, cost-effective, and accurate way of recapitulating the TME. Such novel nanomaterial-based technologies have been of great interest for testing immunotherapies and assessing biomarkers. Finally, we provide a perspective on the developments in artificial intelligence tools to facilitate ICs-based nano theranostics toward cancer immunotherapy.
... Superparamagnetic iron oxide nanoparticles (SPION) are effective vehicles for the delivery of nucleic acids and offer the possibility of monitoring biodistribution. Luo et al. reported the use of a folic acid functionalized polyethyleneimine SPION for siRNA delivery to gastric cancer cells [133]. ...
Simple Summary
Cancer is a multifaceted, life-threatening, and genomically complex disease. The worldwide prevalence of cancer is so high that one in three people will develop cancer during their lifetime. Although the use of RNA therapy is promising to fight cancer, its efficient and safe delivery is still one of the significant challenges hampering its therapeutic application. Thus, the aim of the present review was to highlight the most recent developments in the field of nanomedicine RNA-associated therapies to fight cancer.
Abstract
The complexity, and the diversity of the different types of cancers allied to the tendency to form metastasis make treatment efficiency so tricky and often impossible due to the advanced stage of the disease in the diagnosis. In recent years, due to tremendous scientific breakthroughs, we have witnessed exponential growth in the elucidation of mechanisms that underlie carcinogenesis and metastasis. The development of more selective therapies made it possible to improve cancer treatment. Although interdisciplinary research leads to encouraging results, scientists still have a long exploration journey. RNA technology represents a promise as a therapeutic intervention for targeted gene silencing in cancer, and there are already some RNA-based formulations in clinical trials. However, the use of RNA as a therapeutic tool presents severe limitations, mainly related to its low stability and poor cellular uptake. Thus, the use of nanomedicine employing nanoparticles to encapsulate RNA may represent a suitable platform to address the major challenges hampering its therapeutic application. In this review, we have revisited the potential of RNA and RNA-associated therapies to fight cancer, also providing, as support, a general overview of nanoplatforms for RNA delivery.
... Pd-l1 is a symbol of poor prognosis in gastric cancer (91). Luo et al. developed siRNA delivery systems for PD-L1 knockdown to achieve effective therapy and diagnosis in gastric cancer (92). ...
With the development of materials science and biomedicine, the application of nanomaterials in the medical field is further promoted. In the process of the diagnosis and treatment of diseases, a variety of drugs need to be used. It is an ideal state to make these drugs arrive at a specific location at a specific time and release at a specific speed, which can improve the bioavailability of drugs and reduce the adverse effects of drugs on normal tissues. Traditional drug delivery methods such as tablets, capsules, syrups, and ointments have certain limitations. The emergence of a new nano-drug delivery system further improves the accuracy of drug delivery and the efficacy of drugs. It is well known that the development of the cancer of the stomach is the most serious consequence for the infection of Helicobacter pylori. For the patients who are suffering from gastric cancer, the treatments are mainly surgery, chemotherapy, targeted and immune therapy, and other comprehensive treatments. Although great progress has been made, the diagnosis and prognosis of gastric cancer are still poor with patients usually diagnosed with cancer at an advanced stage. Current treatments are of limited benefits for patients, resulting in a poor 5-year survival rate. Nanomaterials may play a critical role in early diagnosis. A nano-drug delivery system can significantly improve the chemotherapy, targeted therapy, and immunotherapy of advanced gastric cancer, reduce the side effects of the original treatment plan and provide patients with better benefits. It is a promising treatment for gastric cancer. This article introduces the application of nanomaterials in the diagnosis and treatment of H. pylori and gastric cancer.
... For theranostic purposes, Luo et al. loaded PD-L1 siRNA into FA-functionalized PEI superparamagnetic iron oxide NPs. This target-specific nanocarrier with a size of 120 nm facilitated the application of magnetic resonance imaging (MRI) for tumour diagnosis, and the downregulation of PD-L1 resulted in the enhanced secretion of cytokines toward effector T-cell proliferation for gastric cancer treatment [28]. In another study, Pacheo-Torres et al. developed NPs containing a dextran scaffold, PD-L1 siRNA and Cy 5.5 NIR probe, which effectively inhibited the expression of PD-L1 in MDA-MB-231 cells. ...
Although nanomedicines have been in the oncology field for almost three decades with the introduction of doxil, only a few nanomedicine products have reached approval. Can nanotechnology be a realistic tool to reduce the number of hospital beds? At present, several clinically approved anti-PD-1/PD-L1 antibodies or CAR T cell-based therapies are available; however, the immunotherapy field is far from mature. Will immunotherapy be the fourth pillar of cancer treatment? In this review, we summarized the current status of immunotherapy using PD-1/PD-L1-targeting nanocarriers. The knowledge on material science, therapeutic agents and formulation designs could pave the way for high-efficacy treatment outcomes.
... Previous studies have shown that FA conjugated magnetic NPs enhance chemotherapeutic effectiveness and reduce chemotherapy-induced side effects on normal cells. They have selective binding to FR-expressing cancer cells and effective cell internalization via FR-dependent endocytosis (17). In addition, CMD is shown to boost NP gene transfection effectiveness and the development of stable nanocomplexes. ...
Purpose:
The invention and application of new immunotherapeutic methods can compensate for the inefficiency of conventional cancer treatment approaches, partly due to the inhibitory microenvironment of the tumor. In this study, we tried to inhibit the growth of cancer cells and induce anti-tumor immune responses by silencing the expression of the β-catenin in the tumor microenvironment and transmitting interleukin (IL)-15 cytokine to provide optimal conditions for the dendritic cell (DC) vaccine.
Methods:
For this purpose, we used folic acid (FA)-conjugated SPION-carboxymethyl dextran (CMD) chitosan (C) nanoparticles (NPs) to deliver anti-β-catenin siRNA and IL-15 to cancer cells.
Results:
The results showed that the codelivery of β-catenin siRNA and IL-15 significantly reduced the growth of cancer cells and increased the immune response. The treatment also considerably stimulated the performance of the DC vaccine in triggering anti-tumor immunity, which inhibited tumor development and increased survival in mice in two different cancer models.
Conclusions:
These findings suggest that the use of new nanocarriers such as SPION-C-CMD-FA could be an effective way to use as a novel combination therapy consisting of β-catenin siRNA, IL-15, and DC vaccine to treat cancer.
... Among nanomaterials, magnetic nanoparticles find countless applications in various fields. These magnetic nanoparticles are used in ferrofluids as an active component [1], magnetic refrigeration [2,3], catalysis [4,5], biomedicine [6], cancer therapy [7,8], magnetic resonance imaging (MRI) [9,10,11], waste-water treatment [12], nanofluid hyperthermia [13], data storing devices [14], microwave absorption [15], and medical diagnosis [16]. Magnetite and hematite nanoparticles are extensively used in numerous applications, due to their easy availability and superparamagnetic properties [17]. ...
... Based on the diffraction angle (2θ) element name can be identified from table-3. In the XRD pattern of ER70S-2 peaks are identified as Fe3O4andFe2O3 based on their 2θ values [9,29]. Here 2θ=35.53 ...
