Protein-guided biomimetic nanomaterials: a versatile theranostic nanoplatform for biomedical applications.

Over the years, bioinspired mineralization-based approaches have been applied to synthesize multifunctional organic-inorganic nanocomposites. These nanocomposites can address the growing demands of modern biomedical applications. Proteins, serving as vital biological templates, play a pivotal role in the nucleation and growth processes of various organic-inorganic nanocomposites. Protein-mineralized nanomaterials (PMNMs) have attracted significant interest from researchers due to their facile and convenient preparation, strong physiological activity, stability, impressive biocompatibility, and biodegradability. Nevertheless, few comprehensive reviews have expounded on the progress of these nanomaterials in biomedicine. This article systematically reviews the principles and strategies for constructing nanomaterials using protein-directed biomineralization and biomimetic mineralization techniques. Subsequently, we focus on their recent applications in the biomedical field, encompassing areas such as bioimaging, as well as anti-tumor, anti-bacterial, and anti-inflammatory therapies. Furthermore, we discuss the challenges encountered in practical applications of these materials and explore their potential in future applications. This review aspired to catalyze the continued development of these bioinspired nanomaterials in drug development and clinical diagnosis, ultimately contributing to the fields of precision medicine and translational medicine.

Fluoride-Free Synthesis of 2D Titanium Carbide (MXenes) Assisted by scCO2 -Based Ternary Solution.

2D MXene-Ti3 C2 Tx holds great promise in various electronic applications, especially for electromagnetic interference (EMI) shielding devices and supercapacitors. Ti3 C2 Tx synthesis typically involves the use of hazardous fluorine-containing chemicals that can result in the formation of inert fluoride functional groups on the surface of Ti3 C2 Tx , severely degrading its properties and posing a threat to the performance of electron transfer among electrical devices. Herein, a supercritical carbon dioxide-based ternary solution (scCO2 /DMSO/HCl) to produce fluoride-free Ti3 C2 Tx in mild conditions (via 0.5 m HCl, 20 MPa, 32 °C) is reported. The fluorine-free Ti3 C2 Tx films electrode presents an excellent gravimetric capacitance of 320 F g-1 at 2 mV s-1 in 1 m H2 SO4 . Besides, it is demonstrated that fluorine-free Ti3 C2 Tx films exhibit outstanding EMI shielding efficiency of 53.12 dB at 2.5 µm thickness. The findings offer a mild and practical approach to producing fluoride-free Ti3 C2 Tx and open opportunities for exploring MXenes' potential applications in various fields.

NIR-II light triggered burst-release cascade nanoreactor for precise cancer chemotherapy.

The current strategy of co-delivering copper ions and disulfiram (DSF) to generate cytotoxic CuET faces limitations in achieving rapid and substantial CuET production, specifically in tumor lesions. To overcome this challenge, we introduce a novel burst-release cascade reactor composed of phase change materials (PCMs) encapsulating ultrasmall Cu2-xSe nanoparticles (NPs) and DSF (DSF/Cu2-xSe@PCM). Once triggered by second near-infrared (NIR-II) light irradiation, the reactor swiftly releases Cu2-xSe NPs and DSF, enabling catalytic reactions that lead to the rapid and massive production of Cu2-xSe-ET complexes, thereby achieving in situ chemotherapy. The mechanism of the burst reaction is due to the unique properties of ultrasmall Cu2-xSe NPs, including their small size, multiple defects, and high surface activity. These characteristics allow DSF to be directly reduced and chelated on the surface defect sites of Cu2-xSe, forming Cu2-xSe-ET complexes without the need for copper ion release. Additionally, Cu2-xSe-ET has demonstrated a similar (to CuET) anti-tumor activity through increased autophagy, but with even greater potency due to its unique two-dimensional-like structure. The light-triggered cascade of interlocking reactions, coupled with in situ explosive generation of tumor-suppressive substances mediated by the size and valence of Cu2-xSe, presents a promising approach for the development of innovative nanoplatforms in the field of precise tumor chemotherapy.

Human Serum Albumin Based Nanodrug Delivery Systems: Recent Advances and Future Perspective.

With the success of several clinical trials of products based on human serum albumin (HSA) and the rapid development of nanotechnology, HSA-based nanodrug delivery systems (HBNDSs) have received extensive attention in the field of nanomedicine. However, there is still a lack of comprehensive reviews exploring the broader scope of HBNDSs in biomedical applications beyond cancer therapy. To address this gap, this review takes a systematic approach. Firstly, it focuses on the crystal structure and the potential binding sites of HSA. Additionally, it provides a comprehensive summary of recent progresses in the field of HBNDSs for various biomedical applications over the past five years, categorized according to the type of therapeutic drugs loaded onto HSA. These categories include small-molecule drugs, inorganic materials and bioactive ingredients. Finally, the review summarizes the characteristics and current application status of HBNDSs in drug delivery, and also discusses the challenges that need to be addressed for the clinical transformation of HSA formulations and offers future perspectives in this field.

Nanocarrier of Pin1 inhibitor based on supercritical fluid technology inhibits cancer metastasis by blocking multiple signaling pathways.

Cancer metastasis is the primary cause of all cancer-related deaths due to the lack of effective targeted drugs that simultaneously block multiple signaling pathways that drive the dissemination and growth of cancer cells. The unique proline isomerase Pin1 activates numerous cancer pathways, but its role in cancer metastasis and the inhibitory efficacy of Pin1 inhibitors on cancer metastasis are unknown. Moreover, the applicability of Pin1 inhibitor-all-trans retinoic acid (ATRA) is limited due to its several drawbacks. Herein, uniform ATRA-loaded polylactic acid-polyethylene glycol block copolymer nanoparticles (ATRA-NPs) with high encapsulation efficiency, good cellular uptake, excellent controlled release performance and pharmacokinetics are developed using supercritical carbon dioxide processing combined with an optimized design. ATRA-NPs exhibited excellent biosafety and significant inhibition on the growth and metastasis of hepatocellular carcinoma. Pin1 played a key role in cancer metastasis and was the main target of ATRA-NPs. ATRA-NPs exerted their potent anti-metastatic effect by inhibiting Pin1 and then simultaneously blocking multiple signaling pathways and cancer epithelial-mesenchymal progression. Since ATRA-NPs could effectively couple the inhibition of cancer cell dissemination with cancer growth, it provided a novel therapeutic strategy for efficiently inhibiting cancer metastasis.

Immune-regulating camouflaged nanoplatforms: A promising strategy to improve cancer nano-immunotherapy.

Although nano-immunotherapy has advanced dramatically in recent times, there remain two significant hurdles related to immune systems in cancer treatment, such as (namely) inevitable immune elimination of nanoplatforms and severely immunosuppressive microenvironment with low immunogenicity, hampering the performance of nanomedicines. To address these issues, several immune-regulating camouflaged nanocomposites have emerged as prevailing strategies due to their unique characteristics and specific functionalities. In this review, we emphasize the composition, performances, and mechanisms of various immune-regulating camouflaged nanoplatforms, including polymer-coated, cell membrane-camouflaged, and exosome-based nanoplatforms to evade the immune clearance of nanoplatforms or upregulate the immune function against the tumor. Further, we discuss the applications of these immune-regulating camouflaged nanoplatforms in directly boosting cancer immunotherapy and some immunogenic cell death-inducing immunotherapeutic modalities, such as chemotherapy, photothermal therapy, and reactive oxygen species-mediated immunotherapies, highlighting the current progress and recent advancements. Finally, we conclude the article with interesting perspectives, suggesting future tendencies of these innovative camouflaged constructs towards their translation pipeline.

Enhancing the Efficiency of Mild-Temperature Photothermal Therapy for Cancer Assisting with Various Strategies.

Conventional photothermal therapy (PTT) irradiates the tumor tissues by elevating the temperature above 48 °C to exert thermal ablation, killing tumor cells. However, thermal ablation during PTT harmfully damages the surrounding normal tissues, post-treatment inflammatory responses, rapid metastasis due to the short-term mass release of tumor-cellular contents, or other side effects. To circumvent this limitation, mild-temperature photothermal therapy (MTPTT) was introduced to replace PTT as it exerts its activity at a therapeutic temperature of 42-45 °C. However, the significantly low therapeutic effect comes due to the thermoresistance of cancer cells as MTPTT figures out some of the side-effects issues. Herein, our current review suggested the mechanism and various strategies for improving the efficacy of MTPTT. Especially, heat shock proteins (HSPs) are molecular chaperones overexpressed in tumor cells and implicated in several cellular heat shock responses. Therefore, we introduced some methods to inhibit activity, reduce expression levels, and hinder the function of HSPs during MTPTT treatment. Moreover, other strategies also were emphasized, including nucleus damage, energy inhibition, and autophagy mediation. In addition, some therapies, like radiotherapy, chemotherapy, photodynamic therapy, and immunotherapy, exhibited a significant synergistic effect to assist MTPTT. Our current review provides a basis for further studies and a new approach for the clinical application of MTPTT.

Phase-change materials-based platforms for biomedicine.

Recently, phase-change materials (PCMs) have gathered enormous attention in diverse fields of medicine, particularly in bioimaging, therapeutic delivery, and tissue engineering. Due to the excellent physicochemical characteristics and morphological characteristics of PCMs, several developments have been demonstrated in the construction of diverse PCMs-based architectures toward providing new burgeoning opportunities in developing innovative technologies and improving the therapeutic benefits of the existing formulations. However, the fabrication of PCM-based materials into colloidally stable particles remains challenging due to their natural hydrophobicity and high crystallinity. This review systematically emphasizes various PCMs-based platforms, such as traditional PCMs (liposomes) and their nanoarchitectured composites, including PCMs as core, shell, and gatekeeper, highlighting the pros and cons of these architectures for delivering bioactives, imaging anatomical features, and engineering tissues. Finally, we summarize the article with an exciting outlook, discussing the current challenges and future prospects for PCM-based platforms as biomaterials.

A clinical trial of super-stable homogeneous lipiodol-nanoICG formulation-guided precise fluorescent laparoscopic hepatocellular carcinoma resection.

BACKGROUND: Applying traditional fluorescence navigation technologies in hepatocellular carcinoma is severely restricted by high false-positive rates, variable tumor differentiation, and unstable fluorescence performance. RESULTS: In this study, a green, economical and safe nanomedicine formulation technology was developed to construct carrier-free indocyanine green nanoparticles (nanoICG) with a small uniform size and better fluorescent properties without any molecular structure changes compared to the ICG molecule. Subsequently, nanoICG dispersed into lipiodol via a super-stable homogeneous intermixed formulation technology (SHIFT&nanoICG) for transhepatic arterial embolization combined with fluorescent laparoscopic hepatectomy to eliminate the existing shortcomings. A 52-year-old liver cancer patient was recruited for the clinical trial of SHIFT&nanoICG. We demonstrate that SHIFT&nanoICG could accurately identify and mark the lesion with excellent stability, embolism, optical imaging performance, and higher tumor-to-normal tissue ratio, especially in the detection of the microsatellite lesions (0.4 × 0.3 cm), which could not be detected by preoperative imaging, to realize a complete resection of hepatocellular carcinoma under fluorescence laparoscopy in a shorter period (within 2 h) and with less intraoperative blood loss (50 mL). CONCLUSIONS: This simple and effective strategy integrates the diagnosis and treatment of hepatocellular carcinoma, and thus, it has great potential in various clinical applications.

A super-stable homogeneous Lipiodol-hydrophilic chemodrug formulation for treatment of hepatocellular carcinoma.

Background: Though lipiodol formulations are major options in transcatheter arterial chemoembolization (TACE) of advanced unresectable hepatocellular carcinoma (HCC) in the clinic, their application is severely limited by insufficient physical stability between the hydrophobic lipiodol and hydrophilic drugs; thus, most chemotherapeutic drugs are quickly released into systemic circulation resulting in poor therapeutic outcomes and serious side effects. Methods: The typical hydrophilic drug doxorubicin hydrochloride (DOX) was prepared as a pure nanomedicine and then stably and homogeneously dispersed in lipiodol (SHIFT&DOX) via slightly ultrasonic dispersion. The drug release profiles of SHIFT&DOX were defined in a decellularized liver model. In vivo therapeutic studies were performed in rat-bearing N1S1 orthotopic HCC models and rabbit-bearing VX2 orthotopic HCC models. Results: SHIFT&DOX features an ultrahigh homogeneous dispersibility over 21 days, which far surpassed typical Lipiodol-DOX formulations in clinical practice (less than 0.5 h). SHIFT&DOX also has excellent sustained drug release behavior to improve the local drug concentration dependence and increase the time dependence, leading to remarkable embolic and chemotherapeutic efficacy, and eminent safety in all of the orthotopic HCC models. Conclusions: The carrier-free hydrophilic drug nanoparticle technology-based lipiodol formulation provides a promising approach to solve the problem of drug dispersion in TACE with the potential for a translational pipeline.

A pure nanoICG-based homogeneous lipiodol formulation: toward precise surgical navigation of primary liver cancer after long-term transcatheter arterial embolization.

PURPOSE: To surmount the critical issues of indocyanine green (ICG), and thus achieving a precise surgical navigation of primary liver cancer after long-term transcatheter arterial embolization. METHODS: In this study, a facile and green pure-nanomedicine formulation technology is developed to construct carrier-free indocyanine green nanoparticles (nanoICG), and which subsequently dispersed into lipiodol via a super-stable homogeneous lipiodol formulation technology (SHIFT nanoICG) for transcatheter arterial embolization combined near-infrared fluorescence-guided precise hepatectomy. RESULTS: SHIFT nanoICG integrates excellent anti-photobleaching capacity, great optical imaging property, and specific tumoral deposition to recognize tumor regions, featuring entire-process enduring fluorescent-guided precise hepatectomy, especially in resection of the indiscoverable satellite lesions (0.6 mm × 0.4 mm) in rabbit bearing VX2 orthotopic hepatocellular carcinoma models. CONCLUSION: Such a simple and effective strategy provides a promising avenue to address the clinical issue of clinical hepatectomy and has excellent potential for a translational pipeline.

MnO2-coated porous Pt@CeO2 core-shell nanostructures for photoacoustic imaging-guided tri-modal cancer therapy.

We describe the synthesis of MnO2-coated porous Pt@CeO2 core-shell nanostructures (Pt@CeO2@MnO2) as a new theranostic nano-platform. The porous Pt cores endow the core-shell nanostructures with high photothermal conversion efficiency (80%) in the near-infrared region, allowing for photothermal therapy (PTT) and photoacoustic imaging (PA) of tumors. The combination of the Pt core and porous CeO2 interlayer enhances the separation of photo-generated electrons and holes, which is beneficial for the generation of singlet oxygen. With the porous structures of the cores and interlayers, the Pt@CeO2@MnO2 nanostructures are further loaded with an anti-cancer drug (doxorubicin, DOX). The degradation of the MnO2 shell in the tumor microenvironment (TME) can generate O2 for enhanced photodynamic therapy (PDT) and simultaneously trigger DOX release. PA imaging shows good accumulation and retention of DOX-loaded Pt@CeO2@MnO2 in tumors, which guides precise laser irradiation to initiate combined PTT and PDT. The synergistic PTT/PDT/chemotherapy demonstrated by DOX-loaded Pt@CeO2@MnO2 yields remarkable therapeutic outcomes in vitro and in vivo. Taken together, our DOX-loaded Pt@CeO2@MnO2 provides a new avenue for designing high-performance nano-platforms for imaging and therapeutics.

Role of supercritical carbon dioxide (scCO2) in fabrication of inorganic-based materials: a green and unique route.

In recent times, the supercritical carbon dioxide (scCO2) process has attracted increasing attention in fabricating diverse materials due to the attractive features of environmentally benign nature and economically promising character. Owing to these unique characteristics and high-penetrability, as well as diffusivity conditions of scCO2, this high-pressure technology, with mild operation conditions, cost-effective, and non-toxic, among others, is often applied to fabricate various organic and inorganic-based materials, resulting in the unique crystal architectures (amorphous, crystalline, and heterojunction), tunable architectures (nanoparticles, nanosheets, and aerogels) for diverse applications. In this review, we give an emphasis on the fabrication of various inorganic-based materials, highlighting the recent research on the driving factors for improving the quality of fabrication in scCO2, procedures for production and dispersion in scCO2, as well as common indicators utilized to assess quality and processing ability of materials. Next, we highlight the effects of specific properties of scCO2 towards synthesizing the highly functional inorganic-based nanomaterials. Finally, we summarize this compilation with interesting perspectives, aiming to arouse a more comprehensive utilization of scCO2 to broaden the horizon in exploring the green/eco-friendly processing of such versatile inorganic-based materials. Together, we firmly believe that this compilation endeavors to disclose the latent capability and universal prevalence of scCO2 in the synthesis and processing of inorganic-based materials.

Cancer Cytomembrane-Cloaked Prussian Blue Nanoparticles Enhance the Efficacy of Mild-Temperature Photothermal Therapy by Disrupting Mitochondrial Functions of Cancer Cells.

Despite its success against cancer, photothermal therapy (PTT) (>50 °C) suffers from several limitations such as triggering inflammation and facilitating immune escape and metastasis and also damage to the surrounding normal cells. Mild-temperature PTT has been proposed to override these shortcomings. We developed a nanosystem using HepG2 cancer cell membrane-cloaked zinc glutamate-modified Prussian blue nanoparticles with triphenylphosphine-conjugated lonidamine (HmPGTL NPs). This innovative approach achieved an efficient mild-temperature PTT effect by downregulating the production of intracellular ATP. This disrupts a section of heat shock proteins that cushion cancer cells against heat. The physicochemical properties, anti-tumor efficacy, and mechanisms of HmPGTL NPs both in vitro and in vivo were investigated. Moreover, the nanoparticles cloaked with the HepG2 cell membrane substantially prolonged the circulation time in vivo. Overall, the designed nanocomposites enhance the efficacy of mild-temperature PTT by disrupting the production of ATP in cancer cells. Thus, we anticipate that the mild-temperature PTT nanosystem will certainly present its enormous potential in various biomedical applications.

Supercritical fluid (SCF)-assisted fabrication of carrier-free drugs: An eco-friendly welcome to active pharmaceutical ingredients (APIs).

Despite the success in developing various pharmaceutical formulations, most of the active pharmaceutical ingredients (APIs)/drugs, according to the Biopharmaceutics Classification System (BCS), often suffer from various intrinsic limitations of solubility and permeability, substantially hindering their bioavailability in vivo. Regardless of the fact that the availability of different particle fabrication approaches (top-down and bottom-up) towards pharmaceutical manufacturing, the supercritical fluid (SCF) technology has emerged as one of the highly effective substitutes due to the environmentally benign nature and processing convenience, as well as the economically promising character of SCFs. The exceptional features of SCFs have endowed the fabrication of various APIs either solely or in combination with the compatible supramolecular species towards achieving improved drug delivery. Operating such APIs in high-pressure conditions often results in arbitrary-sized particulate forms, ranging from micron-sized to sub-micron/nano-sized particles. Comparatively, these SCF-processed particles offer enhanced tailorable physicochemical and morphological properties (size, shape, and surface), as well as improved performance efficacy (bioavailability and therapy) over the unprocessed APIs. Although the "carrier-based" delivery is practical among diverse delivery systems, the direct fabrication of APIs into suitable particulate forms, referred to as "carrier-free" delivery, has increased attention towards improving the bioavailability and conveying a high payload of the APIs. This review gives a comprehensive emphasis on the SCF-assisted fabrication of diverse APIs towards exploring their great potential in drug delivery. Initially, we discuss various challenges of drug delivery and particle fabrication approaches. Further, different supercritical carbon dioxide (SC-CO2)-based fabrication approaches depending on the character of SCFs are explicitly described, highlighting their advantages and suitability in processing diverse APIs. Then, we provide detailed insights on various processing factors affecting the properties and morphology of SCF-processed APIs and their pharmaceutical applications, emphasizing their performance efficacy when administered through multiple routes of administration. Finally, we summarize this compilation with exciting perspectives based on the lessons learned so far and moving forward in terms of challenges and opportunities in the scale-up and clinical translation of these drugs using this innovative technology.

Genetically engineered magnetic nanocages for cancer magneto-catalytic theranostics.

The clinical applications of magnetic hyperthermia therapy (MHT) have been largely hindered by the poor magnetic-to-thermal conversion efficiency of MHT agents. Herein, we develop a facile and efficient strategy for engineering encapsulin-produced magnetic iron oxide nanocomposites (eMIONs) via a green biomineralization procedure. We demonstrate that eMIONs have excellent magnetic saturation and remnant magnetization properties, featuring superior magnetic-to-thermal conversion efficiency with an ultrahigh specific absorption rate of 2390 W/g to overcome the critical issues of MHT. We also show that eMIONs act as a nanozyme and have enhanced catalase-like activity in the presence of an alternative magnetic field, leading to tumor angiogenesis inhibition with a corresponding sharp decrease in the expression of HIF-1α. The inherent excellent magnetic-heat capability, coupled with catalysis-triggered tumor suppression, allows eMIONs to provide an MRI-guided magneto-catalytic combination therapy, which may open up a new avenue for bench-to-bed translational research of MHT.

Bioinspired red blood cell membrane-encapsulated biomimetic nanoconstructs for synergistic and efficacious chemo-photothermal therapy.

Recently, the fabrication of nanotechnology-based co-delivery systems has garnered enormous interest for efficacious cancer therapy. However, these systems still face certain challenges such as codelivery of drugs with different chemistries, inadequate loading efficiency, immune rejection resulting in rapid clearance and substantially poor bioavailability in vivo. To address the challenges, we have developed a biomimetic and stable design based on bovine serum albumin (BSA) nanoparticles that are encapsulated with a hydrophilic photothermal agent, indocyanine green (ICG), as well as a hydrophobic agent, gambogic acid (GA), via the desolvation method. Furthermore, these nanoconstructs have been coated with the red blood cell membranes (RBCm), which exhibit pronounced long-term circulation in addition to avoiding premature leakage of drugs. RBCm-coated BSA nanoparticles show a higher affinity towards both GA and ICG (RmGIB NPs), resulting in high loading efficiencies of 24.3 ±â€¯1.2 % and 25.0 ±â€¯1.2 %, respectively. Moreover, the bio-efficacy investigations of these biomimetic constructs (RmGIB NPs) in cells in vitro as well as in tumor-bearing mice in vivo confirm augmented inhibition, demonstrating potential synergistic chemo-photothermal therapeutic efficacy. Altogether, we provide an efficient delivery platform for designing and constructing BSA nanovehicles toward synergistic and effective co-delivery of therapeutics.

Recent Advances in Combination of Copper Chalcogenide-Based Photothermal and Reactive Oxygen Species-Related Therapies.

In recent times, the copper chalcogenide (Cu2-xE, E = S, Se, Te, 0 ≤ x ≤ 1)-based nanomaterials have emerged as potent photothermal agents for photothermal therapy (PTT) because of their advantageous features, such as the low cost, reduced toxicity, biodegradability, and strong absorption of near-infrared (NIR) light in a relatively wide range of wavelength. Nevertheless, the applicability of Cu2-xE-based PTT is limited because of its inadequate photothermal conversion efficiency, as well as insufficient destruction of the tumor area unexposed to the NIR laser. Fortunately, Cu2-xE nanomaterials also act as photosensitizers or Fenton-reaction catalysts to produce reactive oxygen species (ROS), referring to ROS-related therapy (RRT), which could further eradicate cancer cells to address the aforementioned limitations of PTT. Moreover, PTT improves RRT based on photodynamic therapy (PDT), sonodynamic therapy (SDT), chemodynamic therapy (CDT), and radiotherapy (RT) in different ways. Inspired by these facts, integrating Cu2-xE-based PTT with RRT into a single nanoplatform seems an ideal strategy to achieve synergistically therapeutic effects for cancer treatment. Herein, we discuss the synergetic mechanisms, composition, and performances of recent nanoplatforms for the combination of Cu2-xE-based PTT and RRT. In addition, we give a brief overview on some specific strategies for the further improvement of Cu2-xE-based PTT and RRT combined cancer treatment to enable the complete eradication of cancer cells, such as realizing the imaging-guided synergistic therapy, promoting deep tumor penetration of the nanosystems, and boosting O2 or H2O2 in the tumor microenvironment. Finally, we summarize with intriguing perspectives, focusing on the future tendencies for their clinical application.

Supercritical Fluid-Assisted Fabrication of Manganese (III) Oxide Hollow Nanozymes Mediated by Polymer Nanoreactors for Efficient Glucose Sensing Characteristics.

Despite their inherent efficacy in significantly accelerating the rate of chemical reactions in biological processes, the applicability of natural enzymes is often hindered because of their intrinsic limitations such as high sensitivity, poor operational stability, and relatively high cost for purification as well as preparation. Thus, the fabrication of catalytically active nanomaterials as artificial enzymes (nanozymes) has become a newly burgeoning area of research in bionic chemistry, aiming in designing functional nanomaterials that mimic various inherent properties of natural enzymes. To address these issues, we present the supercritical fluid (SCF)-assisted fabrication of discrete, monodisperse, and uniform-sized manganese (III) oxide (Mn2O3)-based hollow containers as high-efficiency nanozymes for glucose sensing characteristics. Initially, the core-shell nanoreactors based on polyvinylpyrrolidone (PVP)-encapsulated manganese (III) acetylacetonate (Mn(acac)3) as precursors are fabricated using the SCF technology and subsequent calcination resulted in the Mn2O3 hollow nanoparticles (MHNs). This eco-friendly approach has resulted in the PVP-coated Mn(acac)3 nanoreactors with an average diameter of 220 nm and subsequent calcined hollow products are about one-fifth to that of the precursor. Such MHNs conveniently catalyzed 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2) as a prominent peroxidase mimic, resulting in the oxidation products (TMB*+) at a specific absorption (UV-vis) maxima of 652 nm. Following typical Michaelis-Menten theory, this approach is further utilized to develop visual nonenzymatic sensing of glucose in a linear range of 0.1-1 mM at a detection limit of 2.31 µM. Collectively, this reliable as well as a cost-effective system with high precision potentially allows rapid detection of analytes, providing a convenient way for its utilization in diverse fields.