Micro-nanoemulsion and nanoparticle-assisted drug delivery against drug-resistant tuberculosis: recent developments.

Tuberculosis (TB) is a major global health problem and the second most prevalent infectious killer after COVID-19. It is caused by Mycobacterium tuberculosis (Mtb) and has become increasingly challenging to treat due to drug resistance. The World Health Organization declared TB a global health emergency in 1993. Drug resistance in TB is driven by mutations in the bacterial genome that can be influenced by prolonged drug exposure and poor patient adherence. The development of drug-resistant forms of TB, such as multidrug resistant, extensively drug resistant, and totally drug resistant, poses significant therapeutic challenges. Researchers are exploring new drugs and novel drug delivery systems, such as nanotechnology-based therapies, to combat drug resistance. Nanodrug delivery offers targeted and precise drug delivery, improves treatment efficacy, and reduces adverse effects. Along with nanoscale drug delivery, a new generation of antibiotics with potent therapeutic efficacy, drug repurposing, and new treatment regimens (combinations) that can tackle the problem of drug resistance in a shorter duration could be promising therapies in clinical settings. However, the clinical translation of nanomedicines faces challenges such as safety, large-scale production, regulatory frameworks, and intellectual property issues. In this review, we present the current status, most recent findings, challenges, and limiting barriers to the use of emulsions and nanoparticles against drug-resistant TB.

RNA technology and nanocarriers empowering in vivo chimeric antigen receptor therapy.

The remarkable success of mRNA-based coronavirus 2019 (COVID-19) vaccines has propelled the advancement of nanomedicine, specifically in the realm of RNA technology and nanomaterial delivery systems. Notably, significant strides have been made in the development of RNA-based in vivo chimeric antigen receptor (CAR) therapy. In comparison to the conventional ex vivo CAR therapy, in vivo CAR therapy offers several benefits including simplified preparation, reduced costs, broad applicability and decreased potential for carcinogenic effects. This review summarises the RNA-based CAR constructs in in vivo CAR therapy, discusses the current applications of in vivo delivery vectors and outlines the immune cells edited with CAR molecules. We aim for the conveyed messages to contribute towards the advancement of in vivo CAR application.

Uptake of surface-functionalized thermo-responsive polymeric nanocarriers in corticospinal tract motor neurons.

Nanocarrier drug delivery systems are attractive options for targeted delivery of survival- and regeneration-enhancing therapeutics to neurons damaged by degenerative or traumatic central nervous system (CNS) lesions. Functional groups on nanocarrier surfaces allow derivatization with molecules to target specific cells but may affect cellular interactions and nanocarrier uptake. We synthesized differently sized -COOH and -NH2 surface functionalized polymeric nanocarriers (SFNCs) by emulsion copolymerization and assessed uptake by different cell types in mixed cortical cultures. Following 60-min incubation with SFNCs, mean intensity measurements of fluorescently labeled SFNCs indicated that corticospinal tract motor neurons (CSMNs) took up more COOH- or NH2- functionalized SFNCs with similar sizes (150 nm), compared to glia. However, larger diameter (750 nm) SFNCs were taken up at higher concentrations compared to smaller COOH-derivatized SFNCs (150 nm). These data suggest that larger SFNCs may provide an advantage for enhanced uptake by targeted neurons.

Controlled Fabrication of Unimolecular Micelles as Versatile Nanoplatform for Multifunctional Applications.

Unimolecular micelles (UMs) are nano-sized structures that are composed of single molecules with precise composition. Compared to self-assembled polymeric micelles, UMs possess ultra-stable property even in complex biological environment. With the development of controllable polymerization and coupling chemistry, the preparation of narrowly monodispersed UMs with precise morphology and size has been realized, which further facilitates their multifunctional applications. After brief introduction, state-of-the-art advances in the synthesis and applications of UMs are discussed with an emphasis on their bioapplications. It is believed that these UMs have great potential in future fabrication of multifunctional nanoplatforms.

A Review: Surface Engineering of Lipid-Based Drug Delivery Systems.

This review explores the evolution of lipid-based nanoparticles (LBNPs) for drug delivery (DD). Herein, LBNPs are classified into liposomes and cell membrane-based nanoparticles (CMNPs), each with unique advantages and challenges. Conventional LBNPs possess drawbacks such as poor targeting, quick clearance, and limited biocompatibility. One of the possible alternatives to overcome these challenges is surface modification of nanoparticles (NPs) with materials such as polyethylene glycol (PEG), aptamers, antibody fragments, peptides, CD44, hyaluronic acid, folic acid, palmitic acid, and lactoferrin. Thus, the main focus of this review will be on the different surface modifications that enable LBNPs to have beneficial properties for DD, such as enhancing mass transport properties, immune evasion, improved stability, and targeting. Moreover, various CMNPs are explored used for DD derived from cells such as red blood cells (RBCs), platelets, leukocytes, cancer cells, and stem cells, highlighting their unique natural properties (e.g., biocompatibility and ability to evade the immune system). This discussion extends to the biomimicking of hybrid NPs accomplished through the surface coating of synthetic (mainly polymeric) NPs with different cell membranes. This review aims to provide a comprehensive resource for researchers on recent advances in the field of surface modification of LBNPs and CMNPs. Overall, this review provides valuable insights into the dynamic field of lipid-based DD systems.

A Simple Binary Supramolecular Co-Assembly Platform for Enhanced Tumor Imaging and Therapy.

The primary challenges in tumor imaging and therapy revolve around improving targeting efficiency, enhancing probe/drug delivery efficacy, and minimizing off-target signals and toxicity. Although various carriers have been developed, many are difficult to synthesize, costly, and not universally applicable. Furthermore, numerous carriers exhibit limited delivery rates in solid tumors, particularly larger nanocarriers. To address these challenges, a simple binary co-assembly drug delivery platform has been designed using the readily synthesized small molecule Cys(SEt)-Lys-CBT (CKCBT) as the self-assembly building block. CKCBT can effectively penetrate tumor cells due to its positively charged Lys side chain and small size. Upon glutathione reduction, CKCBT co-assembles with Nile red or Chlorin e6 to form nanofibers inside tumor cells. This enables their specific accumulation in tumor cells rather than normal cells and extends their exposure time, resulting in precise and enhanced tumor imaging and treatment. Hence, this uncomplicated and highly efficient binary co-assembly drug delivery platform can be easily adapted to a broad spectrum of probes and drugs, presenting a novel approach for advancing clinical diagnosis and therapy.

From bench to bedside: the application of cannabidiol in glioma.

Glioma is the most common malignant tumor in central nervous system, with significant health burdens to patients. Due to the intrinsic characteristics of glioma and the lack of breakthroughs in treatment modalities, the prognosis for most patients remains poor. This results in a heavy psychological and financial load worldwide. In recent years, cannabidiol (CBD) has garnered widespread attention and research due to its anti-tumoral, anti-inflammatory, and neuroprotective properties. This review comprehensively summarizes the preclinical and clinical research on the use of CBD in glioma therapy, as well as the current status of nanomedicine formulations of CBD, and discusses the potential and challenges of CBD in glioma therapy in the future.

Exploring non-cytotoxic, antioxidant, and anti-inflammatory properties of selenium nanoparticles synthesized from Gymnema sylvestre and Cinnamon cassia extracts for herbal nanomedicine.

The increasing need for pharmaceutical agents that possess attributes such as safety, cost-effectiveness, environmental sustainability, and absence of side effects has driven the advancement of nanomedicine research, which lies at the convergence of nanotechnology and medicine. AIMS AND OBJECTIVES: The study aimed to synthesize non-toxic selenium nanoparticles (SeNPs) using Gymnema sylvestre (G. sylvestre) and Cinnamon cassia (C. cassia) extracts. It also sought to develop and evaluate versatile nanomedicine formulations i.e. selenium nanoparticles of G. sylvestre and C. cassia (SeNPs), drug (lupeol) loaded SeNPs (DLSeNPs), drug-loaded and coated (PEG) SeNPs (DLCSeNPs) without side effects. METHODS: The SeNPs formulations were hydrothermally synthesized, loaded with lupeol to improve efficacy, coated with polyethylene glycol (PEG) for targeted delivery, and characterized using UV-Vis spectrophotometry, Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), zeta potential analysis, size distribution analysis, and X-ray diffraction (XRD). Hemolytic cytotoxicity, 2,2-Diphenyl-1-picrylhydzayl (DPPH), total Reducing power, and total antioxidant capacity (TAC) antioxidant assays, carrageenan-induced paw edema, and histological studies were used to estimate the acute anti-inflammatory activity of the synthesized SeNPs. RESULTS: The final form of PEGylated and drug (lupeol)-loaded selenium nanoparticles (DLCSeNPs) exhibited an average particle size ranging from 100 to 500 nm as evidenced by SEM, and Zeta potential results. These nanoparticles demonstrated no cytotoxic effects and displayed remarkable antioxidant (IC50 values 19.29) and anti-inflammatory capabilities. These results were fed into Graph-pad Prism 5 software and analyzed by one-way ANOVA, followed by Tukey's post hoc test (p < 0.001). All nano-formulations exhibited significant overall antioxidant activity, with IC50 values ≤ 386 (p < 0.05) as analyzed by ANOVA. The study's results suggest that G. sylvestre outperformed C. cassia in terms of reducing 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical, potassium ferricyanide, and ammonium molybdate in respective antioxidant assays. As far as anti-inflammatory activities are concerned drug (lupeol)-loaded and PEG-coated G. sylvestre SeNPs exhibited the highest anti-inflammatory potential from all other nano-formulations including drug (lupeol)-loaded and PEG-coated C. cassia SeNPs, as exhibited to reduce the release of pro-inflammatory signals i.e. cytokines and NF-kB, making them innovative anti-inflammatory nanomedicine. CONCLUSION: The study synthesized lupeol-loaded and PEG-coated SeNPs, showcasing the potential for biocompatible, cost-effective anti-inflammatory nanomedicines. G. Sylvester's superior antioxidant and anti-inflammatory performance than Cinnamon cassia emphasizes medicinal plant versatility.

Oligonucleotide probes for imaging and diagnosis of bacterial infections.

The rise of infectious diseases as a public health concern has necessitated the development of rapid and precise diagnostic methods. Imaging techniques like nuclear and optical imaging provide the ability to diagnose infectious diseases within the body, eliminating delays caused by sampling and pre-enrichments of clinical samples and offering spatial information that can aid in a more informed diagnosis. Traditional molecular probes are typically created to image infected tissue without accurately identifying the pathogen. In contrast, oligonucleotides can be tailored to target specific RNA sequences, allowing for the identification of pathogens, and even generating antibiotic susceptibility profiles by focusing on drug resistance genes. Despite the benefits that nucleic acid mimics (NAMs) have provided in terms of stabilizing oligonucleotides, the inadequate delivery of these relatively large molecules into the cytoplasm of bacteria remains a challenge for widespread use of this technology. This review summarizes the key advancements in the field of oligonucleotide probes for in vivo imaging, highlighting the most promising delivery systems described in the literature for developing optical imaging through in vivo hybridization.

Selective Interaction of Chiral Carbon Dots with Nucleic Acids: A Promising Nanosensing Platform.

Carbon dots (CDs) represent an emerging class of nanomaterials that combine outstanding photoluminescent properties with low toxicity and excellent biocompatibility. These unique features have garnered significant interest for potential applications in sensing as well as nanovectors for bioactive compounds. Within this context, the possibility of synthesizing chiral carbon dots (CCDs) has paved the way for a plethora of bioapplications in their interaction with chiral biomolecules. In this study we report the synthesis and characterization of CCDs with opposite chiralities and their selective interaction with nucleic acids. A systematic study on their interaction with different oligonucleotides (ODNs) using UV-vis, photoluminescence, and circular dichroism analyses highlighted how the chiral surface of the CCDs induces distinct spectroscopic responses in CCDs-ODN conjugates. These findings establish the foundation for innovative applications of CCDs as nanosensors and nanocarriers for nucleic acids. Additionally, the antioxidant properties of CCDs were investigated, highlighting their dual potential as both sensing and preservative nanomaterials for genetic material. Our results suggest significant implications for the development of chiral-specific diagnostic tools, drug delivery systems, and therapeutic agents. Furthermore, these properties open new avenues for the use of CCDs in antibiotic residue detection, fluorescence imaging, and photodynamic therapy.

CARBON DOTS: Bioimaging and Anticancer Drug Delivery.

Cancer, responsible for approximately 10 million lives annually, urgently requires innovative treatments, as well as solutions to mitigate the limitations of traditional chemotherapy, such as long-term adverse side effects and multidrug resistance. This review focuses on Carbon Dots (CDs), an emergent class of nanoparticles (NPs) with remarkable physicochemical and biological properties, and their burgeoning applications in bioimaging and as nanocarriers in drug delivery systems for cancer treatment. The review initiates with an overview of NPs as nanocarriers, followed by an in-depth look into the biological barriers that could affect their distribution, from barriers to administration, to intracellular trafficking. It further explores CDs' synthesis, including both bottom-up and top-down approaches, and their notable biocompatibility, supported by a selection of in vitro, in vivo, and ex vivo studies. Special attention is given to CDs' role in bioimaging, highlighting their optical properties. The discussion extends to their emerging significance as drug carriers, particularly in the delivery of doxorubicin and other anticancer agents, underscoring recent advancements and challenges in this field. Finally, we showcase examples of other promising bioapplications of CDs, emergent owing to the NPs flexible design. As research on CDs evolves, we envisage key challenges, as well as the potential of CD-based systems in bioimaging and cancer therapy.

Nanocarrier-Integrated Microneedles: Divulging the Potential of Novel Frontiers for Fostering the Management of Skin Ailments.

The various kinds of nanocarriers (NCs) have been explored for the delivery of therapeutics designed for the management of skin manifestations. The NCs are considered as one of the promising approaches for the skin delivery of therapeutics attributable to sustained release and enhanced skin penetration. Despite the extensive applications of the NCs, the challenges in their delivery via skin barrier (majorly stratum corneum) have persisted. To overcome all the challenges associated with the delivery of NCs, the microneedle (MN) technology has emerged as a beacon of hope. Programmable drug release, being painless, and its minimally invasive nature make it an intriguing strategy to circumvent the multiple challenges associated with the various drug delivery systems. The integration of positive traits of NCs and MNs boosts therapeutic effectiveness by evading stratum corneum, facilitating the delivery of NCs through the skin and enhancing their targeted delivery. This review discusses the barrier function of skin, the importance of MNs, the types of MNs, and the superiority of NC-loaded MNs. We highlighted the applications of NC-integrated MNs for the management of various skin ailments, combinational drug delivery, active targeting, in vivo imaging, and as theranostics. The clinical trials, patent portfolio, and marketed products of drug/NC-integrated MNs are covered. Finally, regulatory hurdles toward benchtop-to-bedside translation, along with promising prospects needed to scale up NC-integrated MN technology, have been deliberated. The current review is anticipated to deliver thoughtful visions to researchers, clinicians, and formulation scientists for the successful development of the MN-technology-based product by carefully optimizing all the formulation variables.

Disease-Inspired Design of Biomimetic Tannic Acid-Based Hybrid Nanocarriers for Enhancing the Treatment of Bacterial-Induced Sepsis.

This study explored the development of novel biomimetic tannic acid-based hybrid nanocarriers (HNs) for targeted delivery of ciprofloxacin (CIP-loaded TAH-NPs) against bacterial-induced sepsis. The prepared CIP-loaded TAH-NPs exhibited appropriate physicochemical characteristics and demonstrated biocompatibility and nonhemolytic properties. Computational simulations and microscale thermophoresis studies validated the strong binding affinity of tannic acid (TA) and its nanoformulation to human Toll-like receptor 4, surpassing that of the natural substrate lipopolysaccharide (LPS), suggesting a potential competitive inhibition against LPS-induced inflammatory responses. CIP released from TAH-NPs displayed a sustained release profile over 72 h. The in vitro antibacterial activity studies revealed that CIP-loaded TAH-NPs exhibited enhanced antibacterial efficacy and efflux pump inhibitory activity. Specifically, they showed a 3-fold increase in biofilm eradication activity against MRSA and a 2-fold increase against P. aeruginosa compared to bare CIP. Time-killing assays demonstrated complete bacterial clearance within 8 h of treatment with CIP-loaded TAH-NPs. In vitro DPPH scavenging and anti-inflammatory investigations confirmed the ability of the prepared hybrid nanosystem to neutralize reactive oxygen species (ROS) and modulate LPS-induced inflammatory responses. Collectively, these results suggest that CIP-loaded TAH-NPs may serve as an innovative nanocarrier for the effective and targeted delivery of antibiotics against bacterial-induced sepsis.

Photodynamic Therapy Induced Mitochondrial Targeting Strategies for Cancer Treatment: Emerging Trends and Insights.

The perpetuity of cancer prevalence at a global level calls for development of novel therapeutic approaches with improved targetability and reduced adverse effects. Conventional cancer treatments have a multitude of limitations such as nonselectivity, invasive nature, and severe adverse effects. Chemotherapy is also losing its efficacy because of the development of multidrug resistance in the majority of cancers. To address these issues, selective targeting-based approaches are being explored for an effective cancer treatment. Mitochondria, being the moderator of a majority of crucial cellular pathways like metabolism, apoptosis, and reactive oxygen species (ROS) homeostasis, are an effective targeting site. Mitochondria-targeted photodynamic therapy (PDT) has arisen as a potential approach in this endeavor. By designing photosensitizers (PSs) that preferentially accumulate in the mitochondria, PDT offers a localized technique to induce cytotoxicity in cancer cells. In this review, we intend to explore the crucial principles and challenges associated with mitochondria-targeted PDT, including variability in mitochondrial function, mitochondria-specific PSs, targeted nanocarrier-based monotherapy, and combination therapies. The hurdles faced by this emerging strategy with respect to safety, optimization, clinical translation, and scalability are also discussed. Nonetheless, mitochondria-targeted PDT exhibits a significant capacity in cancer treatment, especially in combination with other therapeutic modalities. With perpetual research and technological advancements, this treatment strategy is a great addition to the arsenal of cancer treatment options, providing better tumor targetability while reducing the damage to surrounding healthy tissues. This review emphasizes the current status of mitochondria-targeted PDT, limitations, and future prospects in its pursuit of safe and efficacious cancer therapy.

Nanosystems with potential application as carriers for skin depigmenting actives.

Hyperpigmentation is a skin disorder characterized by excessive production of melanin in the skin and includes dyschromias such as post-inflammatory hyperchromias, lentigens, melasma and chloasma. Topical products containing depigmenting agents offer a less aggressive treatment option for hyperpigmentation compared to methods like chemical peels and laser sessions. However, some of these agents can cause side effects such as redness and skin irritation. Encapsulating these actives in nanosystems shows promise in mitigating these effects and improving product safety and efficacy. In addition, nanocarriers have the ability to penetrate the skin, potentially allowing for targeted delivery of actives to the affected areas. The most commonly investigated nanosystems are nanoemulsions, vesicular nanosystems and nanoparticles, in which different materials can be used to generate different compositions in order to improve the properties of these nanocarriers. Nanocarriers have already been widely explored, but it is necessary to understand the evolution of these technologies when applied to the treatment of skin hyperchromias. Therefore, this literature review aims to present the state of the art over the last 15 years on the use of nanosystems as a potential strategy for encapsulating depigmenting actives for potential application in cosmetic products for skin hyperchromia. By providing a comprehensive overview of the latest research findings and technological advances, this article can contribute to improving the care and quality of life of people affected by this skin condition.

Telmisartan loaded lipid nanocarrier as a potential repurposing approach to treat glioma: characterization, apoptosis evaluation in U87MG cells, pharmacokinetic and molecular simulation study.

The study explores anticancer potential of telmisartan (TS) loaded lipid nanocarriers (TLNs) in glioma cells as a potential repurposing nanomodality along with estimation of drug availability at rat brain. Experimental TLNs were produced by previously reported method and characterized.In vitroanticancer efficacy of experimental TLNs was estimated by MTT, confocal microscopy, and FACs analysis in glioma cells. Plasma and brain pharmacokinetic (PK) parameters were also analysed by LCMS/MS. Spherical, nanosized, homogenous, unilamellar, TLNs were reported having desirable drug loading (9.5% ± 0.6%), negative zeta potential and sustained TS release tendency. FITC-TLNs were sufficiently internalized into U87MG cells line within 0.5 h incubation period. IC50for TLNs was considerably higher than free TS in the tested glioma cell lines. Further, TLNs induced superior apoptotic effect in U87MG cells than TS. PK (plasma/brain) data depicted higher AUC,Vss, MRT with lower Cltfor TLNs suggesting improved bioavailability,in vivoresidence and sustained drug availability than free TS administration. Docking studies rationalizedin vitro/in vivoresults as preferably higher binding affinity (docking score:12.4) was detected for TS with glioma proteins. Further,in vivostudies in glioma bearing xenograft model is underway for futuristic clinical validation of TLNs.

Nanoparticle-mediated dsRNA delivery for precision insect pest control: a comprehensive review.

Nanoparticle-based delivery systems have emerged as powerful tools in the field of pest management, offering precise and effective means of delivering double-stranded RNA (dsRNA), a potent agent for pest control through RNA interference (RNAi). This comprehensive review aims to evaluate and compare various types of nanoparticles for their suitability in dsRNA delivery for pest management applications. The review begins by examining the unique properties and advantages of different nanoparticle materials, including clay, chitosan, liposomes, carbon, gold and silica. Each material's ability to protect dsRNA from degradation and its potential for targeted delivery to pests are assessed. Furthermore, this review delves into the surface modification strategies employed to enhance dsRNA delivery efficiency. Functionalization with oligonucleotides, lipids, polymers, proteins and peptides is discussed in detail, highlighting their role in improving stability, cellular uptake, and specificity of dsRNA delivery.This review also provides valuable guidance on choosing the most suitable nanoparticle-based system for delivering dsRNA effectively and sustainably in pest management. Moreover, it identifies existing knowledge gaps and proposes potential research directions aimed at enhancing pest control strategies through the utilization of nanoparticles and dsRNA.

Recent advances in the application of gasotransmitters in spinal cord injury.

Spinal Cord Injury (SCI) is a condition characterized by complete or incomplete motor and sensory impairment, as well as dysfunction of the autonomic nervous system, caused by factors such as trauma, tumors, or inflammation. Current treatment methods primarily include traditional approaches like spinal canal decompression and internal fixation surgery, steroid pulse therapy, as well as newer techniques such as stem cell transplantation and brain-spinal cord interfaces. However, the above methods have limited efficacy in promoting axonal and neuronal regeneration. The challenge in medical research today lies in promoting spinal cord neuron regeneration and regulating the disrupted microenvironment of the spinal cord. Studies have shown that gas molecular therapy is increasingly used in medical research, with gasotransmitters such as hydrogen sulfide, nitric oxide, carbon monoxide, oxygen, and hydrogen exhibiting neuroprotective effects in central nervous system diseases. The gas molecular protect against neuronal death and reshape the microenvironment of spinal cord injuries by regulating oxidative, inflammatory and apoptotic processes. At present, gas therapy mainly relies on inhalation for systemic administration, which cannot effectively enrich and release gas in the spinal cord injury area, making it difficult to achieve the expected effects. With the rapid development of nanotechnology, the use of nanocarriers to achieve targeted enrichment and precise control release of gas at Sites of injury has become one of the emerging research directions in SCI. It has shown promising therapeutic effects in preclinical studies and is expected to bring new hope and opportunities for the treatment of SCI. In this review, we will briefly outline the therapeutic effects and research progress of gasotransmitters and nanogas in the treatment of SCI.

Phage-based delivery systems: engineering, applications, and challenges in nanomedicines.

Bacteriophages (phages) represent a unique category of viruses with a remarkable ability to selectively infect host bacteria, characterized by their assembly from proteins and nucleic acids. Leveraging their exceptional biological properties and modifiable characteristics, phages emerge as innovative, safe, and efficient delivery vectors. The potential drawbacks associated with conventional nanocarriers in the realms of drug and gene delivery include a lack of cell-specific targeting, cytotoxicity, and diminished in vivo transfection efficiency. In contrast, engineered phages, when employed as cargo delivery vectors, hold the promise to surmount these limitations and attain enhanced delivery efficacy. This review comprehensively outlines current strategies for the engineering of phages, delineates the principal types of phages utilized as nanocarriers in drug and gene delivery, and explores the application of phage-based delivery systems in disease therapy. Additionally, an incisive analysis is provided, critically examining the challenges confronted by phage-based delivery systems within the domain of nanotechnology. The primary objective of this article is to furnish a theoretical reference that contributes to the reasoned design and development of potent phage-based delivery systems.

In vivo fluorescence imaging of nanocarriers in near-infrared window II based on aggregation-caused quenching.

Accurate fluorescence imaging of nanocarriers in vivo remains a challenge owing to interference derived mainly from biological tissues and free probes. To address both issues, the current study explored fluorophores in the near-infrared (NIR)-II window with aggregation-caused quenching (ACQ) properties to improve imaging accuracy. Candidate fluorophores with NIR-II emission, ACQ984 (λem = 984 nm) and IR-1060 (λem = 1060 nm), from the aza-BODIPY and cyanine families, respectively, were compared with the commercial fluorophore ICG with NIR-II tail emission and the NIR-I fluorophore P2 from the aza-BODIPY family. ACQ984 demonstrates high water sensitivity with complete fluorescence quenching at a water fraction greater than 50%. Physically embedding the fluorophores illuminates various nanocarriers, while free fluorophores cause negligible interference owing to the ACQ effect. Imaging based on ACQ984 revealed fine structures in the vascular system at high resolution. Moreover, good in vivo and ex vivo correlations in the monitoring of blood nanocarriers can be established, enabling real-time noninvasive in situ investigation of blood pharmacokinetics and dynamic distribution in various tissues. IR-1060 also has a good ACQ effect, but the lack of sufficient photostability and steady post-labeling fluorescence undermines its potential for nanocarrier bioimaging. P2 has an excellent ACQ effect, but its NIR-I emission only provides nondiscriminative ambiguous images. The failure of the non-ACQ probe ICG to display the biodistribution details serves as counterevidence for the improved imaging accuracy by NIR-II ACQ probes. Taken together, it is concluded that fluorescence imaging of nanocarriers based on NIR-II ACQ probes enables accurate in vivo bioimaging and real-time in situ pharmacokinetic analysis.