Piezocatalytic therapy is a new‐emerging reactive oxygen species (ROS)‐enabled therapeutic strategy that relies on built‐in electric field and energy‐band bending of piezoelectric materials activated by ultrasound (US) irradiation. Despite becoming a hot topic, material development and mechanism exploration are still underway. Herein, as‐synthesized oxygen‐vacancy‐rich BiO2−x nanosheets (NSs) demonstrate outstanding piezoelectric properties. Under US, a piezo‐potential of 0.25 V for BiO2−x NSs is sufficient to tilt the conduction band to be more negative than the redox potentials of O2/•O2−, •O2−/H2O2, and H2O2/•OH, which initiates a cascade reaction for ROS generation. Moreover, the BiO2−x NSs exhibit peroxidase and oxidase‐like activities to augment ROS production, especially in the H2O2‐overexpressed tumor microenvironment. Density functional theory calculations show that the generated oxygen vacancies in BiO2−x NSs are favorable for H2O2 adsorption and increasing the carrier density to produce ROS. Furthermore, the quick movement of electrons enables an excellent sonothermal effect, for example, rapid rise in temperature to nearly 65 °C upon US with low power (1.2 W cm−2) and short time (96 s). Therefore, this system realizes a multimode synergistic combination of piezocatalytic, enzymatic, and sonothermal therapies, providing a new direction for defect engineering‐optimized piezoelectric materials for tumor therapy.

Oxygen‐Vacancy‐Rich Piezoelectric BiO2−x Nanosheets for Augmented Piezocatalytic, Sonothermal, and Enzymatic Therapies

Metal-organic framework nanoshell structures: Preparation and biomedical applications

Recent Advances of Smart Materials for Ocular Drug Delivery.

Scientific fraternity revealed the potential of stimuli-responsive nanotherapeutics for cancer treatment that aids in tackling the major restrictions of traditionally reported drug delivery systems. Among stimuli-responsive inorganic nanomaterials, metal–organic frameworks (MOFs) have transpired as unique porous materials displaying resilient structures and diverse applications in cancer theranostics. Mainly, it demonstrates tailorable porosity, versatile chemical configuration, tunable size and shape, and feasible surface functionalization, etc. The present review provides insights into the design of stimuli-responsive multifunctional MOFs for targeted drug delivery and bioimaging for effective cancer therapy. Initially, the concept of cancer, traditional cancer treatment, background of MOFs, and approaches for MOFs synthesis have been discussed. After this, applications of stimuli-responsive multifunctional MOFs-assisted nanostructures that include pH, light, ions, temperature, magnetic, redox, ATP, and others for targeted drug delivery and bioimaging in cancer have been thoroughly discussed. As an outcome, the designed multifunctional MOFs showed an alteration in properties due to the exogenous and endogenous stimuli that are beneficial for drug release and bioimaging. The several reported types of stimuli-responsive surface-modified MOFs revealed good biocompatibility to normal cells, promising drug loading capability, target-specific delivery of anticancer drugs into cancerous cells, etc. Despite substantial progress in this field, certain crucial issues need to be addressed to reap the clinical benefits of multifunctional MOFs. Specifically, the toxicological compatibility and biodegradability of the building blocks of MOFs demand a thorough evaluation. Moreover, the investigation of sustainable and greener synthesis methods is of the utmost importance. Also, the low flexibility, off-target accumulation, and compromised pharmacokinetic profile of stimuli-responsive MOFs have attracted keen attention. In conclusion, the surface-modified nanosized design of inorganic diverse stimuli-sensitive MOFs demonstrated great potential for targeted drug delivery and bioimaging in different kinds of cancers. In the future, the preference for stimuli-triggered MOFs will open a new frontier for cancer theranostic applications. 

Stimuli-Responsive Design of Metal-Organic Frameworks for Cancer Theranostics: Current Challenges and Future Perspective.

Metal-organic frameworks (MOFs) hold significant potential as vehicles for drug delivery due to their expansive specific surface area, biocompatibility, and versatile attributes. Concurrently, magnetically actuated micro/nano-robots (MNRs) offer distinct advantages, such as untethered and precise manipulation. The fusion of these technologies presents a promising avenue for achieving non-invasive targeted drug delivery. Here, we report a MOF-based magnetic microrobot swarm (MMRS) for targeted therapy. Our approach overcomes limitations associated with a single MNR, including limited drug loading and the risk of loss during manipulation. We select Zeolitic Imidazolate Framework-8 (ZIF-8) as the drug vehicle for its superior loading potential and pH-sensitive decomposition. Our design incorporates magnetic responsive components into the one-pot synthesis of Fe@ZIF-8, enabling collective behaviors under actuation. Tuning the yaw angle of alternating magnetic fields and nanoparticles' amount, the MMRSs with controllable size achieve instantaneous transformation among different configurations, including vortex-like swarms, chain-like swarms, and elliptical swarms, facilitating adaptation to environmental variations. Transported to the subcutaneous T24 tumor site, the MMRSs with encapsulated doxorubicin (DOX) automatically degrade and release the drug, leading to a dramatic reduction of the tumor in vivo. Our investigation signifies a significant advancement in the integration of biodegradable MOFs into microrobot swarms, ushering in new avenues for accurate and non-invasive targeted drug delivery. 

MOF-based magnetic microrobot swarms for pH-responsive targeted drug delivery

BACKGROUND
Idiopathic central precocious puberty (ICPP) impairs child development, without early intervention. The current reference standard, the gonadotropin-releasing hormone stimulation test, is invasive which may hinder diagnosis and intervention.


PURPOSE
To develop a model for accurate diagnosis of ICPP, by integrating pituitary MRI, carpal bone age, gonadal ultrasound, and basic clinical data.


STUDY TYPE
Retrospective.


POPULATION
A total of 492 girls with PP (185 with ICPP and 307 peripheral precocious puberty [PPP]) were randomly divided by reference standard into training (75%) and internal validation (25%) data. Fifty-one subjects (16 with ICPP, 35 with PPP) provided by another hospital as external validation.


FIELD STRENGTH/SEQUENCE
T1-weighted (spin echo [SE], fast SE, cube) and T2-weighted (fast SE-fat suppression) imaging at 3.0 T or 1.5 T.


ASSESSMENT
Radiomics features were extracted from pituitary MRI after manual segmentation. Carpal bone age, ovarian, follicle and uterine volumes and endometrium presence were assessed from radiographs and gonadal ultrasound. Four machine learning methods were developed: a pituitary MRI radiomics model, an integrated image model (with pituitary MRI, gonadal ultrasound and bone age), a basic clinical model (with age and sex hormone data), and an integrated multimodal model combining all features.


STATISTICAL TESTS
Intraclass correlation coefficients were used to assess consistency of segmentation. Receiver operating characteristic (ROC) curves and the Delong tests were used to assess and compare the diagnostic performance of models. P < 0.05 was considered statistically significant.


RESULTS
The area under of the ROC curve (AUC) of the pituitary MRI radiomics model, integrated image model, basic clinical model, and integrated multimodal model in the training data was 0.668, 0.809, 0.792, and 0.860. The integrated multimodal model had higher diagnostic efficacy (AUC of 0.862 and 0.866 for internal and external validation).


CONCLUSION
The integrated multimodal model may have potential as an alternative clinical approach to diagnose ICPP.


EVIDENCE LEVEL
3.


TECHNICAL EFFICACY
Stage 2.

Development and Validation of a Combined MRI Radiomics, Imaging and Clinical Parameter-Based Machine Learning Model for Identifying Idiopathic Central Precocious Puberty in Girls.

Photodynamic therapy (PDT) is commonly used in choroidal neovascularization (CNV) treatment due to the superior light transmittance of the eye. However, PDT often leads to surrounding tissue damage and further microenvironmental deterioration, including exacerbated hypoxia, inflammation, and secondary neovascularization. In this work, Pt nanoparticles (NPs) and Au NPs decorated zeolitic imidazolate framework‐8 nanoplatform is developed to load indocyanine green for precise PDT and microenvironment amelioration, which can penetrate the internal limiting membrane through Müller cells endocytosis and target to CNV by surface‐grafted cyclo(Arg–Gly–Asp–d‐Phe–Lys) after intravitreal injection. The excessive H2O2 in the CNV microenvironment is catalyzed by catalase‐like Pt NPs for hypoxia relief and enhanced PDT occlusion of neovascular. Meanwhile, Au NPs show significant anti‐inflammatory and anti‐angiogenesis properties in regulating macrophages and blocking vascular endothelial growth factor (VEGF). Compared with verteporfin treatment, the mRNA expressions of hypoxia‐inducible factor‐1α and VEGF in the nanoplatform group are downregulated by 90.2% and 81.7%, respectively. Therefore, the nanoplatform realizes a comprehensive CNV treatment effect based on the high drug loading capacity and biosafety. The CNV treatment mode developed in this work provides a valuable reference for treating other diseases with similar physiological barriers that limit drug delivery and similar microenvironment.

A Novel “Inside‐Out” Intraocular Nanomedicine Delivery Mode for Nanomaterials’ Biological Effect Enhanced Choroidal Neovascularization Occlusion and Microenvironment Regulation

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Papers

Development and Validation of a Combined MRI Radiomics, Imaging and Clinical Parameter-Based Machine Learning Model for Identifying Idiopathic Central Precocious Puberty in Girls.

A Novel “Inside‐Out” Intraocular Nanomedicine Delivery Mode for Nanomaterials’ Biological Effect Enhanced Choroidal Neovascularization Occlusion and Microenvironment Regulation