The relationship between imaging features, therapeutic response, and overall survival in pediatric diffuse intrinsic pontine glioma.

We aimed to evaluate the relationship between imaging features, therapeutic responses (comparative cross-product and volumetric measurements), and overall survival (OS) in pediatric diffuse intrinsic pontine glioma (DIPG). A total of 134 patients (≤ 18 years) diagnosed with DIPG were included. Univariate and multivariate analyses were performed to evaluate correlations of clinical and imaging features and therapeutic responses with OS. The correlation between cross-product (CP) and volume thresholds in partial response (PR) was evaluated by linear regression. The log-rank test was used to compare OS patients with discordant therapeutic response classifications and those with concordant classifications. In univariate analysis, characteristics related to worse OS included lower Karnofsky, larger extrapontine extension, ring-enhancement, necrosis, non-PR, and increased ring enhancement post-radiotherapy. In the multivariate analysis, Karnofsky, necrosis, extrapontine extension, and therapeutic response can predict OS. A 25% CP reduction (PR) correlated with a 32% volume reduction (R2 = 0.888). Eight patients had discordant therapeutic response classifications according to CP (25%) and volume (32%). This eight patients' median survival time was 13.0 months, significantly higher than that in the non-PR group (8.9 months), in which responses were consistently classified as non-PR based on CP (25%) and volume (32%). We identified correlations between imaging features, therapeutic responses, and OS; this information is crucial for future clinical trials. Tumor volume may represent the DIPG growth pattern more accurately than CP measurement and can be used to evaluate therapeutic response.

A chest CT-based nomogram for predicting survival in acute myeloid leukemia.

BACKGROUND: The identification of survival predictors is crucial for early intervention to improve outcome in acute myeloid leukemia (AML). This study aim to identify chest computed tomography (CT)-derived features to predict prognosis for acute myeloid leukemia (AML). METHODS: 952 patients with pathologically-confirmed AML were retrospectively enrolled between 2010 and 2020. CT-derived features (including body composition and subcutaneous fat features), were obtained from the initial chest CT images and were used to build models to predict the prognosis. A CT-derived MSF nomogram was constructed using multivariate Cox regression incorporating CT-based features. The performance of the prediction models was assessed with discrimination, calibration, decision curves and improvements. RESULTS: Three CT-derived features, including myosarcopenia, spleen_CTV, and SF_CTV (MSF) were identified as the independent predictors for prognosis in AML (P < 0.01). A CT-MSF nomogram showed a performance with AUCs of 0.717, 0.794, 0.796 and 0.792 for predicting the 1-, 2-, 3-, and 5-year overall survival (OS) probabilities in the validation cohort, which were significantly higher than the ELN risk model. Moreover, a new MSN stratification system (MSF nomogram plus ELN risk model) could stratify patients into new high, intermediate and low risk group. Patients with high MSN risk may benefit from intensive treatment (P = 0.0011). CONCLUSIONS: In summary, the chest CT-MSF nomogram, integrating myosarcopenia, spleen_CTV, and SF_CTV features, could be used to predict prognosis of AML.

Surface-enhanced Raman scattering-based identification of breast cancer progression using extracellular vesicles-derived integrin α6ß4.

Detection of progression is of great importance to breast cancer treatment and can benefit patients. Limited by current detection technologies and biomarkers, early breast cancer progression diagnosis remains challenging. Researchers have found blood extracellular vesicles (EVs)-derived integrin α6ß4 directly facilitate progression in breast cancer, enabling cancer detection. However, EVs size and heterogeneity hinder protein detection, masked by abundant background EVs. Hence, novel tools for efficient detection of EVs with high selectivity and low interference are significantly desired. Here, a new silver-coated gold nanorods SERS probe, termed as Au@Ag@IDA-B/4MSTP, based on DNA aptamer was established for the detection of integrin α6ß4 derived from EVs. Validation of the Au@Ag@IDA-B/4MSTP probes using cell-culture-derived EVs revealed a LOD of 23 particles/µL for EVs detection. This tool was further confirmed to mimic the real state of cancer with subcutaneous tumor model and lung metastasis model in mice. With 10 µL of blood plasma and simple Raman analysis process, the test achieved 85.7 % sensitivity and 83.3 % specificity. Moreover, our method achieves a simplified approach that expedites the detection process. These results demonstrate the good detection performance of Au@Ag@IDA-B/4MSTP probes for EVs integrin α6ß4, and suggest that this non-invasive approach could be a promising tool for early detection of breast cancer progression.

Hydrogel-based cardiac repair and regeneration function in the treatment of myocardial infarction.

A life-threatening illness that poses a serious threat to human health is myocardial infarction. It may result in a significant number of myocardial cells dying, dilated left ventricles, dysfunctional heart function, and ultimately cardiac failure. Based on the development of emerging biomaterials and the lack of clinical treatment methods and cardiac donors for myocardial infarction, hydrogels with good compatibility have been gradually applied to the treatment of myocardial infarction. Specifically, based on the three processes of pathophysiology of myocardial infarction, we summarized various types of hydrogels designed for myocardial tissue engineering in recent years, including natural hydrogels, intelligent hydrogels, growth factors, stem cells, and microRNA-loaded hydrogels. In addition, we also describe the heart patch and preparation techniques that promote the repair of MI heart function. Although most of these hydrogels are still in the preclinical research stage and lack of clinical trials, they have great potential for further application in the future. It is expected that this review will improve our knowledge of and offer fresh approaches to treating myocardial infarction.

Biomimetic nanomaterials in myocardial infarction treatment: Harnessing bionic strategies for advanced therapeutics.

Myocardial infarction (MI) and its associated poor prognosis pose significant risks to human health. Nanomaterials hold great potential for the treatment of MI due to their targeted and controlled release properties, particularly biomimetic nanomaterials. The utilization of biomimetic strategies based on extracellular vesicles (EVs) and cell membranes will serve as the guiding principle for the development of nanomaterial therapy in the future. In this review, we present an overview of research progress on various exosomes derived from mesenchymal stem cells, cardiomyocytes, or induced pluripotent stem cells in the context of myocardial infarction (MI) therapy. These exosomes, utilized as cell-free therapies, have demonstrated the ability to enhance the efficacy of reducing the size of the infarcted area and preventing ischaemic reperfusion through mechanisms such as oxidative stress reduction, polarization modulation, fibrosis inhibition, and angiogenesis promotion. Moreover, EVs can exert cardioprotective effects by encapsulating therapeutic agents and can be engineered to specifically target the infarcted myocardium. Furthermore, we discuss the use of cell membranes derived from erythrocytes, stem cells, immune cells and platelets to encapsulate nanomaterials. This approach allows the nanomaterials to camouflage themselves as endogenous substances targeting the region affected by MI, thereby minimizing toxicity and improving biocompatibility. In conclusion, biomimetic nano-delivery systems hold promise as a potentially beneficial technology for MI treatment. This review serves as a valuable reference for the application of biomimetic nanomaterials in MI therapy and aims to expedite the translation of NPs-based MI therapeutic strategies into practical clinical applications.

Magnetic resonance imaging-based approaches for detecting the efficacy of combining therapy following VEGFR-2 and PD-1 blockade in a colon cancer model.

BACKGROUND: Angiogenesis inhibitors have been identified to improve the efficacy of immunotherapy in recent studies. However, the delayed therapeutic effect of immunotherapy poses challenges in treatment planning. Therefore, this study aims to explore the potential of non-invasive imaging techniques, specifically intravoxel-incoherent-motion diffusion-weighted imaging (IVIM-DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), in detecting the anti-tumor response to the combination therapy involving immune checkpoint blockade therapy and anti-angiogenesis therapy in a tumor-bearing animal model. METHODS: The C57BL/6 mice were implanted with murine MC-38 cells to establish colon cancer xenograft model, and randomly divided into the control group, anti-PD-1 therapy group, and combination therapy group (VEGFR-2 inhibitor combined with anti-PD-1 antibody treatment). All mice were imaged before and, on the 3rd, 6th, 9th, and 12th day after administration, and pathological examinations were conducted at the same time points. RESULTS: The combination therapy group effectively suppressed tumor growth, exhibiting a significantly higher tumor inhibition rate of 69.96% compared to the anti-PD-1 group (56.71%). The f value and D* value of IVIM-DWI exhibit advantages in reflecting tumor angiogenesis. The D* value showed the highest correlation with CD31 (r = 0.702, P = 0.001), and the f value demonstrated the closest correlation with vessel maturity (r = 0.693, P = 0.001). While the BOLD-MRI parameter, R2* value, shows the highest correlation with Hif-1α(r = 0.778, P < 0.001), indicating the capability of BOLD-MRI to evaluate tumor hypoxia. In addition, the D value of IVIM-DWI is closely related to tumor cell proliferation, apoptosis, and infiltration of lymphocytes. The D value was highly correlated with Ki-67 (r = - 0.792, P < 0.001), TUNEL (r = 0.910, P < 0.001) and CD8a (r = 0.918, P < 0.001). CONCLUSIONS: The combination of VEGFR-2 inhibitors with PD-1 immunotherapy shows a synergistic anti-tumor effect on the mouse colon cancer model. IVIM-DWI and BOLD-MRI are expected to be used as non-invasive approaches to provide imaging-based evidence for tumor response detection and efficacy evaluation.

Mechanism and thermodynamics of scorodite formation by oxidative precipitation from arsenic-bearing solution.

Arsenic pollution is a challenging environmental issue caused by arsenic-bearing wastes from nonferrous metallurgy. Oxidative precipitation via introducing O2 into an ionic Fe(II)-As(V) solution is an advanced method for arsenic immobilization. However, the underlying mechanism is still not well understood. This study proposed a mechanism for scorodite formation by oxidative precipitation, and its thermodynamics were calculated using Gaussian software. Scorodite formation was divided into three stages: precursor formation (3-90 min), oxidative conversion (90-270 min) and crystallization (270-720 min) from the variation in precipitates and solution characterization and parameters such as initial pH, arsenic concentration, and ferrous dosage. In the scorodite formation mechanism, the precursors originate from the coordination polymerization of aqueous Fe(H2O)62+ and H2AsO4-, which contributes to the oxidative conversion of coordinated polymers ([Fe(H2O)4(H2O)]nn+) to basic Fe(H2O)2AsO4 until regular octahedral crystals are formed via nucleation and growth during crystallization. The ΔrGmθ for polymerization varied from -491.96 kJ mol-1 to -33.30 kJ mol-1, and the ΔrGmθ of oxidative conversion changed from -982.16 kJ mol-1 to -224.82 kJ mol-1, demonstrating the feasibility in scorodite formation. This research is significant for understanding scorodite formation in As(V) solutions. It can provide schemes for controlling and modifying the conditions of arsenic-bearing waste immobilization in the laboratories and industries.

Overcoming challenges in the delivery of STING agonists for cancer immunotherapy: A comprehensive review of strategies and future perspectives.

STING (Stimulator of Interferon Genes) agonists have emerged as promising agents in the field of cancer immunotherapy, owing to their excellent capacity to activate the innate immune response and combat tumor-induced immunosuppression. This review provides a comprehensive exploration of the strategies employed to develop effective formulations for STING agonists, with particular emphasis on versatile nano-delivery systems. The recent advancements in delivery systems based on lipids, natural/synthetic polymers, and proteins for STING agonists are summarized. The preparation methodologies of nanoprecipitation, self-assembly, and hydrogel, along with their advantages and disadvantages, are also discussed. Furthermore, the challenges and opportunities in developing next-generation STING agonist delivery systems are elaborated. This review aims to serve as a reference for researchers in designing novel and effective STING agonist delivery systems for cancer immunotherapy.

Space-Time Super-Resolution for Light Field Videos.

Light field (LF) cameras suffer from a fundamental trade-off between spatial and angular resolutions. Additionally, due to the significant amount of data that needs to be recorded, the Lytro ILLUM, a modern LF camera, can only capture three frames per second. In this paper, we consider space-time super-resolution (SR) for LF videos, aiming at generating high-resolution and high-frame-rate LF videos from low-resolution and low-frame-rate observations. Extending existing space-time video SR methods to this task directly will meet two key challenges: 1) how to re-organize sub-aperture images (SAIs) efficiently and effectively given highly redundant LF videos, and 2) how to aggregate complementary information between multiple SAIs and frames considering the coherence in LF videos. To address the above challenges, we propose a novel framework for space-time super-resolving LF videos for the first time. First, we propose a novel Multi-Scale Dilated SAI Re-organization strategy for re-organizing SAIs into auxiliary view stacks with decreasing resolution as the Chebyshev distance in the angular dimension increases. In particular, the auxiliary view stack with original resolution preserves essential visual details, while the down-scaled view stacks capture long-range contextual information. Second, we propose the Multi-Scale Aggregated Feature extractor and the Angular-Assisted Feature Interpolation module to utilize and aggregate information from the spatial, angular, and temporal dimensions in LF videos. The former aggregates similar contents from different SAIs and frames for subsequent reconstruction in a disparity-free manner at the feature level, whereas the latter interpolates intermediate frames temporally by implicitly aggregating geometric information. Compared to other potential approaches, experimental results demonstrate that the reconstructed LF videos generated by our framework achieve higher reconstruction quality and better preserve the LF parallax structure and temporal consistency. The implementation code is available at https://github.com/zeyuxiao1997/LFSTVSR.

Face Blindness in Children and Current Interventions.

Children with prosopagnosia, also known as face blindness, struggle to recognize the faces of acquaintances, which can have a negative impact on their social interactions and overall functioning. This paper reviews existing research on interventions for children with prosopagnosia, including compensatory and remedial strategies, and provides a summary and comparison of their effectiveness. However, despite the availability of these interventions, their effectiveness remains limited and constrained by various factors. The lack of a widely accepted treatment for children with prosopagnosia emphasizes the need for further research to improve intervention strategies. Last, three future research directions were proposed to improve interventions for prosopagnosia, including ecological approaches, the social challenges faced by children, and new potential intervention methods.

Immobilizing arsenic-enriched wastewater from utilization of crude antimony oxides as scorodite using a novel multivalent iron source.

Arsenic-enriched wastewater (A-EW) is a hypertoxic sewage from the utilization of crude antimony oxides in lead anode slime metallurgy. In traditional methods, the H+ accumulation inhibits the arsenic immobilization during scorodite synthesis. In this study, a novel multivalent iron source comprised of Fe(OH)3 and FeSO4·7H2O was proposed to resolve the adverse effects of pH fluctuation during immobilizing A-EW as scorodite. Various approaches, such as scanning electron microscopy and X-ray photoelectron spectroscopy, were applied to characterize the synthesized scorodite. This work was divided into two parts. In thermodynamics, HnAsO4(3-n)- (n = 1, 2, 3) and Fe(OH)n(3-n)+ (n = 0, 1, 2, 3) can feasibly coprecipitate as scorodite according to their △rGm,Tθ ranged from -111.10 kJ mol-1 to -33.53 kJ mol-1. In experimental research, A-EW was immobilized as scorodite by optimizing conditions as initial pH = 2.0, molar ratio of Fe to As = 1.2, molar ratio of Fe(II) to Fe(III) = 4:6, arsenic concentration = 40 g/L, and temperature = 95 °C. The arsenic precipitation ratio is 99.60%, and the micromorphology of synthesized scorodite presents a regular octahedron having size of 5-10 µm. The low leachability of As (0.41 mg/L) in toxicity characteristic leaching procedure (TCLP) confirmed that the prepared scorodite is nonhazardous. The solution pH is stable at 2.0 as the H+ depletion (0.5660 mol) by Fe(OH)3 dissolution and Fe2+ oxidization balanced with that (0.5657 mol) generated from As(V)-Fe(III) coprecipitation. In general, the A-EW was effectively immobilized by proposed multivalent iron source, and can be potentially applied to safely dispose other industrial effluents, such as high arsenic leachates and arsenic-bearing waste acid from nonferrous metallurgy.

How Nanotherapeutic Platforms Play a Key Role in Glioma? A Comprehensive Review of Literature.

Glioblastoma (GBM), a highly aggressive form of brain cancer, is considered one of the deadliest cancers, and even with the most advanced medical treatments, most affected patients have a poor prognosis. However, recent advances in nanotechnology offer promising avenues for the development of versatile therapeutic and diagnostic nanoplatforms that can deliver drugs to brain tumor sites through the blood-brain barrier (BBB). Despite these breakthroughs, the use of nanoplatforms in GBM therapy has been a subject of great controversy due to concerns over the biosafety of these nanoplatforms. In recent years, biomimetic nanoplatforms have gained unprecedented attention in the biomedical field. With advantages such as extended circulation times, and improved immune evasion and active targeting compared to conventional nanosystems, bionanoparticles have shown great potential for use in biomedical applications. In this prospective article, we endeavor to comprehensively review the application of bionanomaterials in the treatment of glioma, focusing on the rational design of multifunctional nanoplatforms to facilitate BBB infiltration, promote efficient accumulation in the tumor, enable precise tumor imaging, and achieve remarkable tumor suppression. Furthermore, we discuss the challenges and future trends in this field. Through careful design and optimization of nanoplatforms, researchers are paving the way toward safer and more effective therapies for GBM patients. The development of biomimetic nanoplatform applications for glioma therapy is a promising avenue for precision medicine, which could ultimately improve patient outcomes and quality of life.

Smart Biomimetic Nanozymes for Precise Molecular Imaging: Application and Challenges.

New nanotechnologies for imaging molecules are widely being applied to visualize the expression of specific molecules (e.g., ions, biomarkers) for disease diagnosis. Among various nanoplatforms, nanozymes, which exhibit enzyme-like catalytic activities in vivo, have gained tremendously increasing attention in molecular imaging due to their unique properties such as diverse enzyme-mimicking activities, excellent biocompatibility, ease of surface tenability, and low cost. In addition, by integrating different nanoparticles with superparamagnetic, photoacoustic, fluorescence, and photothermal properties, the nanoenzymes are able to increase the imaging sensitivity and accuracy for better understanding the complexity and the biological process of disease. Moreover, these functions encourage the utilization of nanozymes as therapeutic agents to assist in treatment. In this review, we focus on the applications of nanozymes in molecular imaging and discuss the use of peroxidase (POD), oxidase (OXD), catalase (CAT), and superoxide dismutase (SOD) with different imaging modalities. Further, the applications of nanozymes for cancer treatment, bacterial infection, and inflammation image-guided therapy are discussed. Overall, this review aims to provide a complete reference for research in the interdisciplinary fields of nanotechnology and molecular imaging to promote the advancement and clinical translation of novel biomimetic nanozymes.

Oligonucleotide nanoassemblies with allyl bromide scaffold-based small molecules.

The development of oligonucleotide nanoassemblies with small molecules has shown great potential in bio-medical applications. However, the interaction of negatively charged oligonucleotides with halogenated small molecules represents a scientific challenge. Here, we introduced a distinct allyl bromide halogenated scaffold, which exhibits specific interaction with adenine nucleic bases of the oligonucleotides, thus leading to the formation of self-assembled nanostructures.

The First-in-Human Whole-Body Dynamic Pharmacokinetics Study of Aptamer.

Serving as targeting ligands, aptamers have shown promise in precision medicine. However, the lack of knowledge of the biosafety and metabolism patterns in the human body largely impeded aptamers' clinical translation. To bridge this gap, here we report the first-in-human pharmacokinetics study of protein tyrosine kinase 7 targeted SGC8 aptamer via in vivo PET tracking of gallium-68 (68Ga) radiolabeled aptamers. The specificity and binding affinity of a radiolabeled aptamer, named 68Ga[Ga]-NOTA-SGC8, were maintained as proven in vitro. Further preclinical biosafety and biodistribution evaluation confirmed that aptamers have no biotoxicity, potential mutation risks, or genotoxicity at high dosage (40 mg/kg). Based on this result, a first-in-human clinical trial was approved and carried out to evaluate the circulation and metabolism profiles, as well as biosafety, of the radiolabeled SGC8 aptamer in the human body. Taking advantage of the cutting-edge total-body PET, the aptamers' distribution pattern in the human body was acquired in a dynamic fashion. This study revealed that radiolabeled aptamers are harmless to normal organs and most of them are accumulated in the kidney and cleared from the bladder via urine, which agrees with preclinical studies. Meanwhile, a physiologically based pharmacokinetic model of aptamer was developed, which could potentially predict therapeutic responses and plan personalized treatment strategies. This research studied the biosafety and dynamic pharmacokinetics of aptamers in the human body for the first time, as well as demonstrated the capability of novel molecular imaging fashion in drug development.

Nanomaterial-Based Antivascular Therapy in the Multimodal Treatment of Cancer.

Abnormal tumor vasculature and a hypoxic tumor microenvironment (TME) limit the effectiveness of conventional cancer treatment. Recent studies have shown that antivascular strategies that focus on antagonizing the hypoxic TME and promoting vessel normalization effectively synergize to increase the antitumor efficacy of conventional therapeutic regimens. By integrating multiple therapeutic agents, well-designed nanomaterials exhibit great advantages in achieving higher drug delivery efficiency and can be used as multimodal therapy with reduced systemic toxicity. In this review, strategies for the nanomaterial-based administration of antivascular therapy combined with other common tumor treatments, including immunotherapy, chemotherapy, phototherapy, radiotherapy, and interventional therapy, are summarized. In particular, the administration of intravascular therapy and other therapies with the use of versatile nanodrugs is also described. This review provides a reference for the development of multifunctional nanotheranostic platforms for effective antivascular therapy in combined anticancer treatments.

Preparation and Characterization of DNA-assembled GRS-DNA-CuS Nanodandelions.

In this study, we introduce a detailed protocol for the preparation of DNA-assembled GRS-DNA-copper sulfide (CuS) nanodandelion, a multifunctional theranostics nanoparticle. Using transmission electron microscope (TEM) and dynamic light scattering techniques, we characterize the physicochemical property of DNA-assembled GRS-DNA-CuS nanodandelions and their dissociation property after the first near-infrared (NIR) light irradiation. In addition, we systematically monitor the processes of tumor accumulation and uniform intratumoral distribution (UITD) of ultrasmall CuS photothermal agents (PAs), which are dissociated from GRS-DNA-CuS nanodandelions, by Raman imaging and photoacoustic imaging, respectively. The UITD of the dissociated ultrasmall CuS PAs can enhance the therapeutic efficiency of photothermal treatment under the second NIR light irradiation. Overall, this protocol provides a powerful tool to achieve UITD of PAs by explosively breaking the hydrogen bonds of DNA in GRS-DNA-CuS nanodandelions under NIR light irradiation. We expect DNA-assembled nanotheranostics to serve as a robust platform for a variety of biomedical applications related to photothermal therapy in the oncology field. This protocol can increase experimental reproducibility and contribute to efficient theranostics nanomedicine.

Near-zero-dispersion soliton and broadband modulational instability Kerr microcombs in anomalous dispersion.

The developing advances of microresonator-based Kerr cavity solitons have enabled versatile applications ranging from communication, signal processing to high-precision measurements. Resonator dispersion is the key factor determining the Kerr comb dynamics. Near the zero group-velocity-dispersion (GVD) regime, low-noise and broadband microcomb sources are achievable, which is crucial to the application of the Kerr soliton. When the GVD is almost vanished, higher-order dispersion can significantly affect the Kerr comb dynamics. Although many studies have investigated the Kerr comb dynamics near the zero-dispersion regime in microresonator or fiber ring system, limited by dispersion profiles and dispersion perturbations, the near-zero-dispersion soliton structure pumped in the anomalous dispersion side is still elusive so far. Here, we theoretically and experimentally investigate the microcomb dynamics in fiber-based Fabry-Perot microresonator with ultra-small anomalous GVD. We obtain 2/3-octave-spaning microcombs with ~10 GHz spacing, >84 THz span, and >8400 comb lines in the modulational instability (MI) state, without any external nonlinear spectral broadening. Such widely-spanned MI combs are also able to enter the soliton state. Moreover, we report the first observation of anomalous-dispersion based near-zero-dispersion solitons, which exhibits a local repetition rate up to 8.6 THz, an individual pulse duration <100 fs, a span >32 THz and >3200 comb lines. These two distinct comb states have their own advantages. The broadband MI combs possess high conversion efficiency and wide existing range, while the near-zero-dispersion soliton exhibits relatively low phase noise and ultra-high local repetition rate. This work complements the dynamics of Kerr cavity soliton near the zero-dispersion regime, and may stimulate cross-disciplinary inspirations ranging from dispersion-controlled microresonators to broadband coherent comb devices.

Artificial Base-Directed In Vivo Assembly of an Albumin-siRNA Complex for Tumor-Targeting Delivery.

RNA interference (RNAi) mediated by short interfering RNA (siRNA) is a promising method for cancer treatment, but the clinical application is hampered by several limitations, including metabolic instability, lack of tumor specificity, and poor cellular uptake. To meet these challenges, we have explored the possibility of structure modification of siRNA with artificial bases for property optimization. A series of siRNAs functionalized with different numbers of hydrophobic base F are prepared for screening. The interactions of plasma proteins with F-base-modified siRNA (F-siRNA) are investigated, and it is identified that the interaction with serum albumin is dominant. Experiments revealed that the introduction of F bases conferred modified siRNA with improved tumor-specific accumulation, prolonged circulatory retention time, and better tissue permeability. Mechanistic studies indicated that the F base induces the formulation of a stable siRNA-albumin complex, which transports siRNA to tumor tissues selectively owing to an enhanced permeability and retention (EPR) effect of albumin. The F base also facilitates the binding of siRNA to transport-associated proteins on the cell membrane, enabling its cellular internalization. Together, these data demonstrate that F base modification confers siRNA-enhanced cellular uptake and biostability and specific accumulation in tumor tissue, which provides a new approach for the development of siRNA-based cancer therapeutics.