Breast cancer remains one of the most prevalent malignant tumors affecting women worldwide and continues posing a major threat to global health. Current clinical treatments include surgery, chemotherapy, radiotherapy, targeted therapy, and endocrine therapy. However, these strategies are frequently limited by challenges such as drug resistance, elevated toxicity, adverse effects, and inadequate modulation of the tumor microenvironment (TME). Recent developments in nanotechnology have enabled the application of nanomaterial-based drug delivery systems that significantly improve delivery efficiency and biocompatibility, reduce drug toxicity and side effects, and demonstrate potential anticancer effects by modulating the TME. Hydrogels, a class of drug carriers, are characterized by a three-dimensional polymer network with high water absorption and retention capacity. Owing to their favorable biocompatibility, degradability, tissue-like physical properties, environmental responsiveness, and functional flexibility, hydrogels have been extensively utilized in biomedical applications, including bone regeneration, wound healing, antibacterial treatments, biosensing, and tumor therapy. Despite these advantages, hydrogels and nanomaterials still confront significant challenges when applied in breast cancer therapy. The integration of functional nanomaterials into the hydrogel matrix can form a novel multifunctional system. This transformation allows hydrogels to serve as targeted delivery platforms for anticancer nanodrugs, enabling synergistic therapeutic effects. This systematic review summarizes recent advances in hydrogel-based nanomaterials for breast cancer therapy, with emphasis on design strategies, mechanisms of action, and immunomodulatory applications. It also critically discusses current limitations and prospects of hydrogel-based nanomaterials. The objective of this review is to help lower interdisciplinary barriers and accelerate the clinical translation of hydrogel-based technologies toward safer, more personalized breast cancer treatments.

Aggregation-induced emission (AIE)-active fluorescent probes have emerged as promising tools for in vivo biomarker detection and biological imaging due to their unconventional emission behavior in aggregated state. In this study, we designed novel imidazole-based aggregation-induced emission luminogens (AIEgens), TPIT, featuring a symmetrical donor-π-bridge-acceptor-π-bridge-donor (D-π-A-π-D) backbone. By introducing benzothiadiazole (BT)-derived acceptors with different electron-withdrawing capabilities and steric hindrance, a series of AIEgens (TPIT-B, TPIT-P, TPIT-N) were successfully synthesized, exhibiting tunable emission windows from red (641 nm) to near-infrared (NIR) region (802 nm), typical AIE characteristics, significant Stokes shifts (> 120 nm ) and remarkable reactive oxygen species (ROS) generation efficiency. In further animal experiments, TPIT-N nanoparticles (NPs) achieved high-contrast NIR imaging of osteosarcoma (OS) tissues. Our preliminary findings reveal that the optical performance of TPIT can be facilely modulated to meet specific requirements by rational selection of acceptor cores. This flexible molecular engineering strategy endows TPIT with board potential in medical diagnostics, tumor treatments and other biological applications.

Radionuclide therapy (RNT) uses the ionizing radiation generated by the emitted particles during radioactive decay to directly damage DNA structure or indirectly increase the concentration of free radicals in cells, thereby destroying or killing diseased cells. Radionuclides offer the advantages of high sensitivity, non-invasive, and functional imaging in clinical diagnosis. The key to RNT is to deliver sufficient radiation dose to tumors while reducing toxic side effects on normal tissues and organs. However, most radionuclides are unable to reach the lesion site, and the radiation dose is not sufficient to completely kill cancer cells. In recent years, the rapid development of nanotechnology has provided new ideas for the design of radiopharmaceuticals. Compared to small molecules, nanomaterials have the advantages of a larger specific surface area, more labeling sites, good biocompatibility, and a longer blood circulation time. Moreover, the combination of the unique intrinsic properties of nanomaterials with radionuclides can construct multifunctional carriers, which achieve mutual complementarity. In this paper, we summarize the research progress of nanomaterials in tumor radionuclide therapy (including radionuclide therapy, radionuclide/chemo therapy, radionuclide/immuno therapy, radionuclide/photothermal therapy, radionuclide/photodynamic therapy, and radionuclide/chemodynamic therapy) and prospect the future development and challenges of nano-radiopharmaceuticals.

Gene therapy aims to modify or manipulate gene expression and change the biological characteristics of living cells to achieve the purpose of treating diseases. The safe, efficient, and stable expression of exogenous genes in cells is crucial for the success of gene therapy, which is closely related to the vectors used in gene therapy. Currently, gene therapy vectors are mainly divided into two categories: viral vectors and non-viral vectors. Viral vectors are widely used due to the advantages of persistent and stable expression, high transfection efficiency, but they also have certain issues such as infectivity, high immunological rejection, randomness of insertion mutation, carcinogenicity, and limited vector capacity. Non-viral vectors have the advantages of non-infectivity, controllable chemical structure, and unlimited vector capacity, but the transfection efficiency is low. With the rapid development of nanotechnology, the unique physicochemical properties of nanomaterials have attracted increasing attention in the field of drug and gene delivery. Among many nanomaterials, iron-based nanomaterials have attracted much attention due to their superior physicochemical properties, such as Fenton reaction, magnetic resonance imaging, magnetothermal therapy, photothermal therapy, gene delivery, magnetically-assisted drug delivery, cell and tissue targeting, and so on. In this paper, the research progress of iron-based nanomaterials in gene delivery and tumor gene therapy is reviewed, and the future application direction of iron-based nanomaterials is further prospected.

We investigate the ultrafast carrier dynamics and spin–lattice interaction in strained and unstrained LaMnO3 films via temperature-dependent femtosecond transient optical spectroscopy. The transient reflectivity measurements show two characteristic relaxation processes in both types of films, which are attributed to electron–phonon coupling and phonon-assisted spin–lattice interaction, respectively. The carrier dynamics and coupling between lattice and spin system are well described with the three-temperature model; the spin–lattice relaxation time constant is dominated by the temperature-dependent spin specific heat. Both the electron–phonon coupling and the spin–lattice interaction are enhanced in the strained film, as a result of the modified band structure and orbital ordering under biaxial compressive strain. Our results reveal the critical role of strain in the photo-induced dynamical interactions in LaMnO3.

Persistent luminescent nanoparticles (PLNPs) are photoluminescent materials that can still emit luminescence after the cessation of the excitation light source. In recent years, due to their unique optical properties, the PLNPs have attracted extensive attention in the biomedical field. Since the PLNPs effectively eliminate autofluorescence interference from biological tissues, many researchers have contributed a lot of work in the fields of biological imaging and tumor therapy. This article mainly introduces the synthesis methods of the PLNPs and their progress in the application of biological imaging and tumor therapy, as well as the challenges and development prospects.

Small extracellular vesicle–derived microRNAs (sEV-miRNAs) have emerged as promising noninvasive biomarkers for early cancer diagnosis. Herein, we developed a molecular probe based on three-dimensional (3D) multiarmed DNA tetrahedral jumpers (mDNA-Js)-assisted DNAzyme activated by Na+, combined with a disposable paper-based electrode modified with a Zr-MOF–rGO–Au NP nanocomplex (ZrGA) to fabricate a novel biosensor for sEV-miRNAs Assay. Zr-MOF tightly wrapped by rGO was prepared via a one-step method, and it effectively aids electron transfer and maximizes the effective reaction area. In addition, the mechanically rigid, and nanoscale-addressable mDNA-Js assembled from the bottom up ensure the distance and orientation between fixed biological probes as well as avoid probe entanglement, considerably improving the efficiency of molecular hybridization. The fabricated bioplatform achieved the sensitive detection of sEV-miR-21 with a detection limit of 34.6 aM and a dynamic range from100 aM to 0.2 µM. In clinical blood sample tests, the proposed bioplatform showed results highly consistent with those of qRT-PCRs and the signal increased proportionally with the NSCLC staging. The proposed biosensor with a portable wireless USB-type analyzer is promising for the fast, easy, low-cost, and highly sensitive detection of various nucleic acids and their mutation derivatives, making it ideal for POC biosensing.

I-III-VI ternary quantum dots (QDs) have emerged as favorable alternatives to the toxic II-VI QDs for optoelectronic and biological applications. However, their use as optical gain media for microlasers is still limited by a low fluorescence efficiency. Here, we demonstrate amplified spontaneous emission (ASE) and lasing from colloidal QDs of Zn-processed AgIn5S8 (AIS) for the first time. The passivation treatment on the AIS QDs yields a 3.4-fold enhancement of fluorescence quantum efficiency and a 30% increase in the two-photon absorption cross section. ASE is achieved from the AIS/ZnS core/shell QD films under both one- and two-photon pumping with a threshold fluence of ∼84.5 μJ/cm2 and 3.1 mJ/cm2, respectively. These thresholds are comparable to the best optical gain performance of Cd based-QDs reported in the literature. Moreover, we demonstrate a facile whispering-gallery-mode microlaser of the core/shell QDs with a lasing threshold of ∼233 μJ/cm2. The passivated AIS QDs can be promising optical gain media for photonic applications.

Kidney dysfunction is a clinical syndrome that can subsequently result in lethal kidney failure. The exploration of emerging bioimaging contrast agents with translational potential is highly challenging for a feasible diagnosis of kidney dysfunction. Herein, a class of renal-clearable gadolinium nanoparticles (Gd@PEG NPs) with an ultrasmall size of ∼5 nm, good monodispersity, and T1 relaxivity are synthesized using mesoporous silica nanoparticles as the template. Assisted by such renal-clearable Gd@PEG NPs, the diagnosis of kidney dysfunction in a mice model with a damaged kidney has been achieved through in vivo noninvasive magnetic resonance imaging. As a result, this work paves the way to synthesize monodispersible ultrasmall Gd contrast agents, facilitating the exploration of translational strategies for an in vivo analysis of kidney dysfunction.

Designing a highly sensitive, fast response, cheap, and flexible biosensing platform has important significance in the diagnosis of diabetes. Herein, we developed an ultra-fast and sensitive glucose sensor based on CuO nanoflowers-coated stereo-graphene electrode on carbon cloth. The three-dimensional graphene (3DG) nanostructures were established on the carbon cloth (CC) by radio frequency plasma enhanced chemical vapor deposition (RF-PECVD), and CuO nanoflowers subsequently obtained via chemical deposition. The prepared CuO@3DG@CC electrode with self-assembled structures provided abundant ion diffusion channels, large specific surface area and high conductivity, which shows an ultrasensitive current response to glucose. The detection limit of the sensor is as low as 0.068 mu M and the response efficiency is as fast as 0.5 s. The electrode has two linear ranges with 0.5-115.5 mu M and 165.5-1165.5 mu M and has a strong anti-interference ability and shows an excellent stability. This kind of flexible enzyme-free glucose sensor has been successfully applied to the detection of glucose in actual serum samples and shows a good accuracy, which is likely be applied to the medical testing field and the commercial production and has potential to further applied in wearable sensors.

The endothelial barrier plays an essential role in health and disease by protecting organs from toxins while allowing nutrients to access the circulation. However, it is the major obstacle that limits the delivery of therapeutic drugs to the diseased tissue. Here, it is reported for the first time that near-infrared (NIR) laser pulses can transiently promote the delivery of semiconducting polymer nanoparticles passing the vascular barrier via photoacoustic-effect-induced accumulation, only by the aid of pulse laser irradiation. This strategy enables selective and substantial accumulation of the NIR-absorbing nanoparticles inside specific tissues, implying the discovery of an unprecedented approach for light-controlled nanoparticle delivery. Especially, the nanoparticle delivery in solid tumors by 10-min laser scanning is approximately six times higher than that of the enhanced permeability and retention (EPR) effect in 24 h under current experimental conditions. Further results confirm that this strategy facilitates substantial accumulation of nanoparticles in the mouse brain with intact skull. This approach thus opens a new door for tissue-specific delivery of nanomaterials with an unprecedented level of efficiency and precision.

One major challenge in miRNA-based therapy is to explore facile delivery strategies, which can facilitate the efficient and precise accumulation of intrinsically instable microRNAs (miRNAs) at targeted tumor sites. To address this critical issue, for the first time we demonstrate that a near-infrared (NIR) pulse laser can guide efficient delivery of miRNAs mediated by a NIR-absorbing and photoacoustic active semiconducting polymer (SP) nanocarrier, which can generate photoacoustic radiation force to intravascularly overcome the endothelial barriers. Importantly, we demonstrate an ultrafast delivery of miRNA (miR-7) to tumor tissues under the irradiation of pulse laser in 20 min, showing a 5-fold boosted efficiency in comparison to the traditional passive targeting strategy. The delivered miR-7 acts as a sensitizer of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and synergizes with TRAIL-inducing compound (TIC), leading to sustained TRAIL upregulation for effective tumor suppression in mice. As such, our results indicate that the NIR-absorbing semiconducting polymer-mediated nanocarrier platform can significantly enhance the targeted delivery efficiency of therapeutic miRNAs to tumors, resulting in potent tumor growth inhibition.

Exploration of facile strategies for precise regulation of target gene expression remains highly challenging in the development of gene therapies. Especially, a stimuli-responsive nanocarrier integrated with ability of noninvasive remote control for treating wide types of cancers is rarely developed. Herein, a NIR-II absorbing semiconducting polymer (PBDTQ) is employed to remotely activate the heat-inducible heat-shock protein 70 (HSP70) promoter under laser irradiation, further realizing regulation of gene-directed enzyme prodrug therapy (GDEPT) for cancer treatment in mild hyperthermia. In this multifunctional nanocomposite, the PBDTQ and double suicide gene plasmid (pSG) based on HSP70 promoter are incorporated into a lipid complex. Upon NIR-II laser excitation, the mild photothermal effect (≈43 °C) generated from PBDTQ can cause the release of pSG and activation of HSP70 promoter, and then upregulate suicide gene expression triggered by the HSP70 promoter which can further convert the nontoxic prodrug into its cytotoxic metabolites. Therefore, this work demonstrates a universal NIR-II laser-triggered GDEPT using semiconducting polymers as the photothermal generator for cancer treatment with minimized collateral damage and nontargeted side effects.

To date, the strategic exploration of a synthetic approach to afford persistent luminescent nanoparticles (PLNPs) integrated with precisely controlled size/monodispersity and renal-clearable capability remains extremely challenging. Herein, we report a facile synthetic process with an elucidated mechanism to fine-tune the size for acquiring renal-clearable PLNPs, using mesoporous silica nanoparticles (MSNs) as a template. This strategy relies on the controlled crystallization of the precursor ions in the pore channels of MSNs at a high temperature, leading to the formation of monodispersed PLNPs with an average diameter as small as 2.5 nm after complete removal of MSN templates. The as-prepared ultrasmall PLNPs coated with polyethylene glycol exhibit uniform size, excellent water-dispersibility, good persistent luminescence, and high T1 relaxivity (17.6 mM-1·S-1), ensuring their suitability for afterglow/magnetic resonance dual-modality imaging and subsequent in vivo renal clearance. Thus, our study provides a strategy to inspire the controlled synthesis of diverse PLNPs by using MSN templates, simultaneously addressing the critical issues of precise adjustment of size and body clearance for versatile biomedical applications.

Precise and efficient delivery of nanomedicine to the target site has remained as a major roadblock in advanced cancer treatment. Here, a novel photoacoustic force (PAF)-guided nanotherapeutic system is reported based on a near-infrared (NIR)-absorbing semiconducting polymer (SP), showing significantly improved tumor accumulation and deep tissue penetration for enhanced phototherapeutic efficacy. The accumulation of nanoparticles in 4T1 tumor-bearing mice induced by the PAF strategy displays a fivefold enhancement in comparison with that of the traditional passive targeting pathway, in a significantly shortened time (45 min vs 24 h) with an enhanced penetration depth in tumors. Additionally, a tumor-bearing mouse model is rationally designed to unveil the mechanism, indicating that the nanoparticles enter solid tumors through enhanced transportation across blood vessel barriers via both inter-endothelial gaps and active trans-endothelial pathways. This process is specifically driven by PAF generated from the nanoparticles under NIR laser irradiation. The study thus demonstrates a new nanotherapeutic strategy with low dose, enhanced delivery efficiency in tumor, and boosted therapeutic efficacy, opening new doors for designing novel nanocarriers.

The endothelial barrier plays an essential role in health and disease by protecting organs from toxins while allowing nutrients to access the circulation. However, it is the major obstacle that limits the delivery of therapeutic drugs to the diseased tissue. Here, for the first time we show that near-infrared (NIR) laser pulses can transiently open the vascular barrier via photoacoustic force, enabling selective and substantial accumulation of nanoparticles inside specific tissues. The nanoparticle delivery in tumors by 10-minute laser scanning is ~6 times higher than that of the enhanced permeability and retention (EPR) effect in 24 hours under current experimental conditions. We further show substantial accumulation of nanoparticles in the mouse brain with intact skull through light-controlled opening of the blood-brain barrier (BBB). This approach opens a new door for tissue-specific delivery of nanomaterials with an unprecedented level of efficiency and precision.

Magnetic resonance imaging (MRI) has gained wide interest in early accurate diagnoses due to the high resolution and low toxicity of magnetic nanoparticles. In order to develop potential alternatives of toxic Gd- or Mn-based chelating agents, we report the synthesis of water soluble ultra-small Fe3O4 nanoparticles by a modified co-precipitation method as T1-weighted positive contrast agents. The magnetic iron oxide nanoparticles (MIONs) were functionalized by polymer ligand dodecanthiol-polymethacrylic acid (DDT-PMAA) to enhance their colloidal stability. These MIONs have high longitudinal relaxivity (r1 = 8.18 mM−1·S−1) and exhibited good results in the in vitro and in vivo MR imaging. No toxicity was observed in cytotoxicity assay and histology toxicity analysis. The MIONs@DDT-PMAA(magnetic iron oxide nanoparticles @ dodecanthiol-polymethacrylic acid) present great potential as positive contrast agents for tumor diagnosis.

A fluorometric and magnetic resonance (MR) dual-modal detection scheme is presented for determination of ascorbic acid (AA). It is based on the use of a blended Au/MnO2@BSA mixture that was prepared via a biomimetic strategy, using bovine serum albumin (BSA) as the template at physiological temperature. The MnO2@BSA fraction (one part of the composite) is not susceptible to MR but can be degraded to MR-active compounds upon a redox reaction with even ultralow concentrations of AA. In parallel, the blended Au/MnO2@BSA recovers its fluorescence because MnO2@BSA acts as a quencher of the fluorescence of circumjacent Au@BSA (the other part of the composite). Fluorescence typically is measured at excitation/emission wavelengths of 470/625 nm. Leveraging on this redox reaction between MnO2 and AA, a dual-mode detection scheme for AA was developed. Both the fluorescence and the MR signal increase with the concentration of AA. The lowest limit for the detection of AA is 0.6 μM in the fluorometric mode and 0.4 μM in the MR mode. Analysis of AA-spiked serum samples showed that the recoveries obtained by either the fluorometric and MR mode can reach 94%. This is the first report of the use of blended nanoparticles with their inherent cross-validation regularity.