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Designing efficient and cost-effective materials is pivotal to solving the key scientific and technological challenges at the interface of energy, environment, and sustainability for achieving NetZero. Two-dimensional transition metal dichalcogenides (2D TMDs) represent a unique class of materials that have catered to a myriad of energy conversion and storage (ECS) applications. Their uniqueness arises from their ultra-thin nature, high fractions of atoms residing on surfaces, rich chemical compositions featuring diverse metals and chalcogens, and remarkable tunability across multiple length scales. Specifically, the rich electronic/electrical, optical, and thermal properties of 2D TMDs have been widely exploited for electrochemical energy conversion (e.g., electrocatalytic water splitting), and storage (e.g., anodes in alkali ion batteries and supercapacitors), photocatalysis, photovoltaic devices, and thermoelectric applications. Furthermore, their properties and performances can be greatly boosted by judicious structural and chemical tuning through phase, size, composition, defect, dopant, topological, and heterostructure engineering. The challenge, however, is to design and control such engineering levers, optimally and specifically, to maximize performance outcomes for targeted applications. In this review we discuss, highlight, and provide insights on the significant advancements and ongoing research directions in the design and engineering approaches of 2D TMDs for improving their performance and potential in ECS applications.
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BACKGROUND: Adenotonsillectomy is one of the most common surgical procedures worldwide. The current standard for securing the airway in patients undergoing adenotonsillectomy is endotracheal tube (ETT) intubation. Several studies have investigated the use of the laryngeal mask airway (LMA) in this procedure. We conducted a systematic review and meta-analysis to compare the safety and efficacy of the LMA versus ETT in adenotonsillectomy. METHOD: Databases were searched from inception to 2022 for randomized controlled trials and comparative studies. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The primary outcome is the rate of perioperative respiratory adverse events (PRAEs). Secondary outcomes included the rate of conversion to ETT, desaturations, nausea/vomiting, and surgical time. A subgroup analysis, risk of bias, publication bias, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessments were also performed. RESULTS: Twelve studies were included in the analysis (4176 patients). The mean overall conversion to ETT was 8.36% [95% confidence interval (CI) = 8.17, 8.54], and for the pediatric group 8.27% (95% CI = 8.08, 8.47). The mean rate of conversion to ETT secondary to complications was 2.89% (95% CI = 2.76, 3.03) while the rest was from poor surgical access. Overall, there was no significant difference in PRAEs [odds ratio (OR) 1.16, 95% CI = 0.60, 2.22], desaturations (OR 0.79, 95% CI = 0.38, 1.64), or minor complications (OR 0.89, 95% CI = 0.50, 1.55). The use of LMA yielded significantly shorter operative time (mean difference -4.38 minutes, 95% CI = -8.28, -0.49) and emergence time (mean difference -4.15 minutes, 95% CI = -5.63, -2.67). CONCLUSION: For adenotonsillectomy surgery, LMA is a safe alternative to ETT and requires less operative time. Careful patient selection and judgment of the surgeon and anesthesiologist are necessary, especially given the 8% conversion to ETT rate.
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Adenoidectomia , Máscaras Laríngeas , Tonsilectomia , Humanos , Tonsilectomia/efeitos adversos , Tonsilectomia/métodos , Adenoidectomia/efeitos adversos , Adenoidectomia/métodos , Máscaras Laríngeas/efeitos adversos , Intubação Intratraqueal , Complicações Pós-Operatórias/epidemiologiaRESUMO
Nanostructured 7-9-residue cyclic and unstructured lipopeptide-based facial detergents have been engineered to stabilize the model integral membrane protein, bacteriorhodopsin. Formation of a cylindrical-type micelle assembly induced by facial amphipathic lipopeptides resembles a biological membrane more effectively than conventional micelles. The hydrophobic face of this cylindrical-type micelle provides extended stability to the membrane protein and the hydrophilic surface interacts with an aqueous environment. In our present study, we have demonstrated experimentally and computationally that lipopeptide-based facial detergents having an unstructured or ß-turn conformation can stabilize membrane proteins. However, constrained peptide detergents can provide enhanced stability to bacteriorhodopsin. In this study, we have computationally examined the structural stability of bacteriorhodopsin in the presence of helical, beta-strand, and cyclic unstructured peptide detergents, and conventional detergent-like peptides. Our study demonstrates that optimal membranomimetics (detergents) for stabilizing a specific membrane protein can be screened based on the following criteria: (i) hydrodynamic radii of the self-assembled peptide detergents, (ii) stability assay of detergent-encased membrane proteins, (iii) percentage covered area of detergent-encased membrane proteins obtained computationally and (iv) protein-detergent interaction energy.
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Bacteriorodopsinas , Lipopeptídeos , Nanoestruturas , Estabilidade Proteica , Bacteriorodopsinas/química , Nanoestruturas/química , Lipopeptídeos/química , Detergentes/química , Micelas , Interações Hidrofóbicas e HidrofílicasRESUMO
Background and objective Anemia, particularly iron deficiency anemia (IDA), presents a significant global health challenge, particularly among children under the age of five years in developing nations. Concurrently, febrile convulsions (FC) affect up to 5% of neurologically healthy children aged 6-60 months, causing considerable distress among parents. There is a suggested correlation between fever and iron deficiency, which may exacerbate neurological risks, potentially lowering seizure thresholds and increasing the risk of FC. However, studies investigating the relationship between IDA and FC have shown conflicting results. In light of this, this study aimed to explore this relationship among children aged 6-60 months in Eastern India, an area where this association has yet to be thoroughly investigated. Materials and methods The case-control study included children aged 6-60 months. The cases consisted of children presenting with FC, while controls comprised children in the same age group presenting with febrile illness but without seizures. Informed consent was obtained, a detailed history was taken, and clinical examinations were conducted for both groups. Blood investigations were performed to diagnose IDA according to WHO criteria: hemoglobin <11 gm/dl with the classical triad of low mean corpuscular volume (MCV), low mean corpuscular hemoglobin (MCH), and low mean corpuscular hemoglobin concentration (MCHC) for age. Data analysis was performed using the R-based software Jamovi 2.4.8. with appropriate statistical tests. Results We included 81 cases and 80 controls. The study found a statistically significant association between IDA and FC with an odds ratio (OR) of 2.25 [95% confidence interval (CI): 1.03-4.91; p=0.039]. Additionally, the study revealed that hemoglobin levels, MCH, MCV, and MCHC were lower among cases compared to controls, while the red cell distribution width (RDW) was higher. Both these findings regarding RBC indices were statistically significant (p<0.05). Conclusions Our findings indicate a statistically significant association between IDA and FC among children under five years of age. Implementing measures to prevent IDA and strengthening existing strategies may help alleviate the burden of FC in this vulnerable population.
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Understanding the emergent electronic structure in twisted atomically thin layers has led to the exciting field of twistronics. However, practical applications of such systems are challenging since the specific angular correlations between the layers must be precisely controlled and the layers have to be single crystalline with uniform atomic ordering. Here, an alternative, simple, and scalable approach is suggested, where nanocrystallinetwo-dimensional (2D) film on 3D substrates yields twisted-interface-dependent properties. Ultrawide-bandgap hexagonal boron nitride (h-BN) thin films are directly grown on high in-plane lattice mismatched wide-bandgap silicon carbide (4H-SiC) substrates to explore the twist-dependent structure-property correlations. Concurrently, nanocrystalline h-BN thin film shows strong non-linear second-harmonic generation and ultra-low cross-plane thermal conductivity at room temperature, which are attributed to the twisted domain edges between van der Waals stacked nanocrystals with random in-plane orientations. First-principles calculations based on time-dependent density functional theory manifest strong even-order optical nonlinearity in twisted h-BN layers. This work unveils that directly deposited 2D nanocrystalline thin film on 3D substrates could provide easily accessible twist-interfaces, therefore enabling a simple and scalable approach to utilize the 2D-twistronics integrated in 3D material devices for next-generation nanotechnology.
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Diamond surface functionalization has received significant research interest recently. Specifically, H-termination has been widely adopted because it endows the diamond surface with negative electron affinity and the hole carrier is injected in the presence of surface transfer dopants. Exploring different functional groups' attachment on diamond surfaces and their impact on the electronic structure, using wet and dry chemical approaches, would hence be of interest in engineering diamond as a semiconductor. Here, we report the functionalization of the H-terminated diamond surface with nitrogen and sulfur heteroatoms. Surface characterization of functionalized diamond surfaces shows that these groups are well-distributed and covalently bonded to diamonds. Four chemical functional groups (-SH, -S-S-, -S-O, and -S=O) were found on the sulfurized diamond surface, and two groups (-NH2 and =NH) upon amination. We also report co-functionalization of surface with N and S (N-S), where sulfurization promotes sequential amination efficiency with reduced exposure time. Electrical measurement shows that heteroatom-modified diamond surfaces possess higher conductivity than H-terminated diamonds. Density functional theory (DFT) shows that upon functionalization with various N/S ratios, the conduction band minimum and valence band maximum downshift, which lowers the bandgap in comparison to an H-terminated diamond. These observations suggest the possibility of heteroatom functionalizations with enhanced surface electrical conductivity on the diamond that are useful for various electronic applications.
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RNA interference based therapeutic gene silencing is an emerging platform for managing highly metastatic breast cancer. Cytosolic delivery of functional siRNA remains the key obstacle for efficient RNAi therapy. To overcome the challenges of siRNA delivery, we have engineered a vitamin E-tethered, short, optimum protease stabilized facial lipopeptide based non-immunogenic, biocompatible siRNA transporter to facilitate the clinical translation in future. Our designed lipopeptide has an Arginine-Sarcosine-Arginine segment for providing optimum protease-stability, minimizing adjacent arginine-arginine repulsion and reducing intermolecular aggregation and α-tocopherol as the lipidic moiety for facilitating cellular permeabilization. Interestingly, our designed non-immunogenic siRNA transporter has exhibited significantly better long term transfection efficiency than HiPerFect and can transfect hard to transfect primary cell line, HUVEC. Our engineered siRNA therapeutics demonstrated high efficacy in managing metastasis against triple negative breast cancer by disrupting the crosstalk of endothelial cells and MDA-MB-231 and reduced stemness and metastatic markers, as evidenced by downregulating critical oncogenic pathways. Our study aimed at silencing Notch1 signalling to achieve "multi-targeted" therapy with a single putative molecular medicine. We have further developed mechanistically rational combination therapy combining Notch1 silencing with a repurposed drug m-TOR inhibitor, metformin, which demonstrated synergistic interaction and enhanced antitumor efficacy against cancer metastasis.
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mRNA-based vaccines and candidate therapeutics have great potential in various medical fields. For the delivery of mRNA into target cells and tissues, lipid formulations are often employed. However, this approach could cause the activation of immune responses, making it unsuitable for the treatment of inflammatory conditions. Therefore, alternative delivery systems are highly demanded. In this study, we evaluated the transport efficiency and characteristics of cell-penetrating peptide PepFect14 (PF14) and mRNA nanoparticles in the presence of different additives. Our results show that all PF14-mRNA formulations entered cultured cells, while calcium chloride enhanced the transport and production of the encoded protein in HeLa and HaCaT cell lines, and polysorbate 80 did so in primary human keratinocytes. All formulations had similar physical properties and did not remarkably affect cell viability. By selectively blocking endocytosis pathways, we show that PF14-mRNA nanoparticles primarily entered HeLa cells via macropinocytosis and HaCaT cells via both macropinocytosis and clathrin-mediated endocytosis, while none of the blockers significantly affected the delivery into primary keratinocytes. Finally, subcutaneous injection of PF14-mRNA nanoparticles before inducing mouse irritant contact dermatitis resulted in the expression of a reporter protein without provoking harmful immune responses in the skin. Together, our findings suggest that PF14-mRNA nanoparticles have the potential for developing mRNA-based therapeutics for treating inflammatory skin conditions.
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Boron nitride (BN) is an exceptional material, and among its polymorphs, two-dimensional (2D) hexagonal and three-dimensional (3D) cubic BN (h-BN and c-BN) phases are most common. The phase stability regimes of these BN phases are still under debate, and phase transformations of h-BN/c-BN remain a topic of interest. Here, we investigate the phase stability of 2D/3D h-BN/c-BN nanocomposites and show that the coexistence of two phases can lead to strong nonlinear optical properties and low thermal conductivity at room temperature. Furthermore, spark-plasma sintering of the nanocomposite shows complete phase transformation to 2D h-BN with improved crystalline quality, where 3D c-BN possibly governs the nucleation and growth kinetics. Our demonstration might be insightful in phase engineering of BN polymorph-based nanocomposites with desirable properties for optoelectronics and thermal energy management applications.
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The room temperature growth of two-dimensional van der Waals (2D-vdW) materials is indispensable for state-of-the-art nanotechnology. Low temperature growth supersedes the requirement of elevated growth temperatures accompanied with high thermal budgets. Moreover, for electronic applications, low or room temperature growth reduces the possibility of intrinsic film-substrate interfacial thermal diffusion related deterioration of the functional properties and the consequent deterioration of the device performance. Here, we demonstrated the growth of ultrawide-bandgap boron nitride (BN) at room temperature by using the pulsed laser deposition (PLD) process, which exhibited various functional properties for potential applications. Comprehensive chemical, spectroscopic and microscopic characterizations confirmed the growth of ordered nanosheet-like hexagonal BN (h-BN). Functionally, the nanosheets show hydrophobicity, high lubricity (low coefficient of friction), and a low refractive index within the visible to near-infrared wavelength range, and room temperature single-photon quantum emission. Our work unveils an important step that brings a plethora of potential applications for these room temperature grown h-BN nanosheets as the synthesis can be feasible on any given substrate, thus creating a scenario for "h-BN on demand" under a frugal thermal budget.
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Silicon photonics is rapidly evolving as an advanced chip framework for implementing quantum technologies. With the help of silicon photonics, general-purpose programmable networks with hundreds of discrete components have been developed. These networks can compute quantum states generated on-chip as well as more extraordinary functions like quantum transmission and random number generation. In particular, the interfacing of silicon photonics with complementary metal oxide semiconductor (CMOS) microelectronics enables us to build miniaturized quantum devices for next-generation sensing, communication, and generating randomness for assembling quantum computers. In this review, we assess the significance of silicon photonics and its interfacing with microelectronics for achieving the technology milestones in the next generation of quantum computers and quantum communication. To this end, especially, we have provided an overview of the mechanism of a homodyne detector and the latest state-of-the-art of measuring squeezed light along with its integration on a photonic chip. Finally, we present an outlook on future studies that are considered beneficial for the wide implementation of silicon photonics for distinct data-driven applications with maximum throughput.
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Cell-penetrating peptides (CPPs) are highly promising transfection agents that can deliver various compounds into living cells, including nucleic acids (NAs). Positively charged CPPs can form non-covalent complexes with negatively charged NAs, enabling simple and time-efficient nanoparticle preparation. However, as CPPs have substantially different chemical and physical properties, their complexation with the cargo and characteristics of the resulting nanoparticles largely depends on the properties of the surrounding environment, i.e., solution. Here, we show that the solvent used for the initial dissolving of a CPP determines the properties of the resulting CPP particles formed in an aqueous solution, including the activity and toxicity of the CPP-NA complexes. Using different biophysical methods such as dynamic light scattering (DLS), atomic force microscopy (AFM), transmission and scanning electron microscopy (TEM and SEM), we show that PepFect14 (PF14), a cationic amphipathic CPP, forms spherical particles of uniform size when dissolved in organic solvents, such as ethanol and DMSO. Water-dissolved PF14, however, tends to form micelles and non-uniform aggregates. When dissolved in organic solvents, PF14 retains its α-helical conformation and biological activity in cell culture conditions without any increase in cytotoxicity. Altogether, our results indicate that by using a solvent that matches the chemical nature of the CPP, the properties of the peptide-cargo particles can be tuned in the desired way. This can be of critical importance for in vivo applications, where CPP particles that are too large, non-uniform, or prone to aggregation may induce severe consequences.
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Small interfering RNA (siRNA) has become the cornerstone against undruggable targets and for managing metastatic breast cancer. However, an effective gene silencing approach is faced with a major challenge due to the delivery problem. In our present study, we have demonstrated efficient siRNA delivery, superior gene silencing, and inhibition of metastasis in triple-negative breast cancer cells (MDA-MB-231) using rod-shaped (aspect ratio: 4) multivalent peptide-functionalized gold nanoparticles and compared them to monovalent free peptide doses. Multivalency is a new concept in biology, and tuning the physical parameters of multivalent nanoparticles can enhance gene silencing and antitumor efficacy. We explored the effect of the multivalency of shape- and size-dependent peptide-functionalized gold nanoparticles in siRNA delivery. Our study demonstrates that peptide functionalization leads to reduced toxicity of the nanoparticles. Such designed peptide-functionalized nanorods also demonstrate antimetastatic efficacy in Notch1-silenced cells by preventing EMT progression in vitro. We have shown siRNA delivery in the hard-to-transfect primary cell line HUVEC and also demonstrated that the Notch1-silenced MDA-MB-231 cell line has failed to form nanobridge-mediated foci with the HUVEC in the co-culture of HUVEC and MDA-MB-231, which promote metastasis. This antimetastatic effect is further checked in a xenotransplant in vivo zebrafish model. In vivo studies also suggest that our designed nanoparticles mediated inhibition of micrometastasis due to silencing of the Notch1 gene. The outcome of our study highlights that the structure-activity relationship of multifunctional nanoparticles can be harnessed to modulate their biological activity.
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Nanopartículas Metálicas , Nanotubos , Neoplasias , Animais , Linhagem Celular Tumoral , Inativação Gênica , Ouro , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Peixe-Zebra/genética , Humanos , Neoplasias da Mama/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Metástase NeoplásicaRESUMO
The engineering of exceptional points (EPs) in open optical systems has lately attracted much attention for developing future all-optical devices. However, investigation of the fascinating features of EPs in fiber geometries is lacking. We design a fabrication feasible dual-core optical fiber segment, where non-Hermiticity in terms of a symmetric customized gain-loss profile is introduced to modulate the interaction between two corresponding coupled modes toward hosting a dynamical EP encirclement scheme in the gain-loss parameter space. An asymmetric conversion process between two supported modes is reported by exploiting the chirality of the encountered EP. The proposed scheme can lead to an advanced platform to design mode-manipulative all-optical components in communication and all-fiber photonic devices.
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High-performance nonvolatile resistive random access memories (ReRAMs) and their small stimuli control are of immense interest for high-speed computation and big-data processing in the emerging Internet of Things (IoT) arena. Here, we examine the resistive switching (RS) behavior in growth-controlled HfO2/La0.67Sr0.33MnO3 (LSMO) heterostructures and their tunability in a low magnetic field. It is demonstrated that oxygen-deficient HfO2 films show bipolar switching with a high on/off ratio, stable retention, as well as good endurance owing to the orthorhombic-rich phase constitution and charge (de)trapping-enabled Schottky-type conduction. Most importantly, we have demonstrated that RS can be tuned by a very low externally applied magnetic field (â¼0-30 mT). Remarkably, application of a magnetic field of 30 mT causes RS to be fully quenched and frozen in the high resistive state (HRS) even after the removal of the magnetic field. However, the quenched state could be resurrected by applying a higher bias voltage than the one for initial switching. This is argued to be a consequence of the electronically and ionically "active" nature of the HfO2-x/LSMO interface on both sides and its susceptibility to the electric and low magnetic field effects. This result could pave the way for new designs of interface-engineered high-performance oxitronic ReRAM devices.
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A dermal absorption model for small and macromolecules was previously proposed by Ibrahim et al. This model estimated absorption of therapeutics from the dermal tissue based on their molecular size and protein binding through blood and lymphatics. Blood absorption followed a two-pore theory and the lymphatic absorption was limited by the constant lymphatic flow rate. Current work builds on this steady-state concept by modeling the absorption from the dermis immediately after an injection is given (unsteady state). An injection in the dermis creates a localized pressure gradient which resolves itself over time. This phenomenon is captured in the model to estimate the impact of injection volume on the absorption rate constant. Blood absorption follows the two-pore theory but is time-dependent and the lymphatic absorption is determined based on valve opening and pressure driven convective flow, returning to steady-state as the molecule is absorbed. A direct comparison of the steady-state analysis, experimental data and the current model is made. The results indicate that accounting for the localized time-varying pressure can better predict the experimental absorption rate constants. This work significantly improves the existing understanding of macromolecule uptake from the interstitial fluid following intradermal injection.
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Modelos Biológicos , Preparações Farmacêuticas , Transporte Biológico , Derme , Líquido Extracelular/metabolismo , Preparações Farmacêuticas/metabolismoRESUMO
Parkinson's disease (PD) is a neuromotor disorder, primarily manifested by motor anomalies due to progressive loss of dopaminergic neurons. Although alterations in genetic factors have been linked with its etiology, exponential accumulation of environmental entities such as reactive oxygen species (ROS) initiate a cyclic chain reaction resulting in accumulation of cellular inclusions, dysfunctional mitochondria, and overwhelming of antioxidant machinery, thus accelerating disease pathogenesis. Involvement of oxidative stress in PD is further substantiated through ROS induced Parkinsonian models and elevated oxidative markers in clinical PD samples; thereby, making modulation of neuronal oxidative load as one of the major approaches in management of PD. Here we have found a potent antioxidant moiety Scopoletin (Sp), a common derivative in most of the nootropic herbs, with robust neuroprotective ability. Sp increased cellular resistance to ROS through efficient recycling of GSH to prevent oxidative damage. The Sp treated cells showed higher loads of reduced glutathione making them resistant to perturbation of antioxidant machinery or neurotoxin MPP+. Sp could restore the redox balance, mitochondrial function, and prevented oxidative damage, leading to recovery of dopaminergic neural networks and motion abilities in Drosophila genetic model of PD. Our data also suggest that Sp, in combination increases the therapeutic potency of L-DOPA by mitigating its chronic toxicity. Together, we highlight the possible ability of Sp in preventing oxidative stress mediated loss of dopaminergic neurons and at the same time enhance the efficacy of dopamine recharging regimens.
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Dopamina/metabolismo , Drosophila/genética , Glutationa/metabolismo , Doença de Parkinson/genética , Escopoletina/uso terapêutico , Animais , Humanos , Estresse Oxidativo , Doença de Parkinson/mortalidade , Escopoletina/farmacologia , Análise de SobrevidaRESUMO
The dynamics and control of charge transfer between optoelectronically interesting and size-tunable halide perovskite quantum dots and other juxtaposed functional electronic materials are important issues for the emergent device interest involving such a family of materials in heterostructure configurations. Herein, we have grown bimetallic Au-Ag thin films on glass by pulsed laser deposition at room temperature, which bear nanoparticulate character, and the corresponding optical absorption spectra reveal the expected surface plasmon resonance signature(s). Subsequently, spin-coated CsPbBr3 nanoparticle films onto the bimetallic Au-Ag films exhibit surface-enhanced Raman scattering as well as strong photoluminescence quenching, the latter reflecting highly efficient transfer of photo-generated carriers across the CsPbBr3/Au-Ag interface. Surprisingly, when an ultrathin MgO (insulating) layer of optimum thickness is introduced between the CsPbBr3 and Au-Ag films, the charge transfer is further facilitated with the average lifetime of carriers becoming even shorter. By changing the thickness of the thin MgO layer, the carrier lifetime can in fact be tuned; with the charge transfer getting fully blocked for thick enough MgO layers, as expected. Our study thus throws light on the charge-carrier dynamics in halide perovskites, which is of importance to emergent optoelectronic applications.
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Several new structurally diverse carbonyl functional group-based iodoantimonate organic-inorganic hybrid crystals are synthesized using an in situ formed oxonium cationic precursor. These crystals exhibit interesting optoelectronic properties consistent with DFT calculations. Charge transfer and photoluminescence quenching between these crystals and Au nanoparticulate films are examined for potential application interest.
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Cytosolic delivery of functional siRNA remains the major challenge to develop siRNA-based therapeutics. Designing clinically safe and effective siRNA transporter to deliver functional siRNA across the plasma and endosomal membrane remains a key hurdle. With the aim of improving endosomal release, we have designed cyclic and linear peptide-based transporters having an Arg-DHis-Arg template. Computational studies show that the Arg-DHis-Arg template is also stabilized by the Arg-His side-chain hydrogen bonding interaction at physiological pH, which dissociates at lower pH. The overall atomistic interactions were examined by molecular dynamics simulations, which indicate that the extent of peptide_siRNA assembly formation depends greatly on physicochemical properties of the peptides. Our designed peptides having the Arg-DHis-Arg template and two lipidic moieties facilitate high yield of intracellular delivery of siRNA. Additionally, unsaturated lipid, linoleic acid moieties were introduced to promote fusogenicity and facilitate endosomal release and cytosolic delivery. Interestingly, such protease-resistant peptides provide serum stability to siRNA and exhibit high efficacy of erk1 and erk2 gene silencing in the triple negative breast cancer (TNBC) cell line. The peptide having two linoleyl moieties demonstrated comparable efficacy with commercial transfection reagent HiPerFect, as evidenced by the erk1 and erk2 gene knockdown experiment. Additionally, our study shows that ERK1/2 silencing siRNA and doxorubicin-loaded gramicidin-mediated combination therapy is more effective than siRNA-mediated gene silencing-based monotherapy for TNBC treatment.