Monitoring Of Drug Release Research Articles

Temperature-Responsive Hydrogel System Integrating Wound Temperature Monitoring and On-demand Drug Release for Sequentially Inflammatory Process Regulation of Wound Healing.

Wound healing faces challenges like inflammation, infection, and limited monitoring capabilities, and traditional dressings often lack the ability to promote healing or provide real-time wound status updates. Early pro-inflammatory responses help clear pathogens and damaged tissue, while timely anti-inflammatory modulation aids tissue regeneration, making sequential inflammation regulation crucial. Additionally, wound temperature, a key infection biomarker, enables real-time monitoring for effective management. We propose a temperature-responsive hydrogel dressing capable of two-stage sequential drug release and wound temperature monitoring. The hydrogel, composed of poly(N-isopropylacrylamide) (PNIPAM) and dopamine/methacrylated-modified hyaluronic acid (HA-MA-DA), allows temperature-based drug release control, sequential regulating pro-inflammatory and anti-inflammatory stages in wound healing. Interleukin-8 (IL-8), a pro-inflammatory molecule, is encapsulated into hydrogel matrix and rapidly released to trigger the initial inflammatory response. Furthermore, photothermally responsive and erastin-loaded polydopamine@PNIPAM nanoparticles (E-PD NPs) are incorporated to release the anti-inflammatory drug erastin upon near-infrared light exposure, terminating inflammation through cytosolic burial, and thus achieve anti-inflammatory effects at the second stage of wound healing. Furthermore, a bluetooth module enables real-time wound temperature monitoring. Combining sequential drug release with temperature monitoring, our hydrogel dressing addresses significant gaps in current wound healing technologies and offers new insights into personalized therapeutic interventions.

Azo-linked 5-ASA-coumarin prodrug: Fluorescent tracking for colonic drug release in UC treatment

Theranostic prodrugs that enable real-time, non-invasive monitoring of drug release and biodistribution are highly desirable for optimizing therapeutic efficacy and guiding personalized medication. Herein, we report a colon-targeted theranostic prodrug system (P1) for the simultaneous delivery and tracking of 5-aminosalicylic acid (5-ASA) in the treatment of ulcerative colitis (UC). P1 comprises a fluorescent 7-amino-4-methylcoumarin (7-AMC) reporter covalently linked to 5-ASA via an azo bond, which quenches the fluorescence of 7-AMC until P1 is activated by azoreductases in the colonic microenvironment. This selective activation triggers the release of 5-ASA and the revival of 7-AMC fluorescence, enabling real-time monitoring of drug delivery. To improve the solubility and targeted delivery of P1, it was encapsulated within polymeric micelles (PM) that selectively adhere to the positively charged, inflamed colonic tissues. In vitro studies confirmed the stability, biocompatibility, and selective activation of P1 under simulated colonic conditions. Notably, in a mouse model of UC, the P1-loaded PM achieved targeted delivery of 5-ASA to the inflamed colon, resulting in effective attenuation of colitis symptoms. Importantly, the in situ activation of P1 allowed for the real-time, non-invasive visualization of drug release and biodistribution, providing valuable insights for treatment optimization. This theranostic prodrug approach offers a promising strategy for the simultaneous therapy and tracking of 5-ASA delivery in UC treatment, with the potential to facilitate personalized medication and improve therapeutic outcomes.

Visualization of the degradation of long-acting microneedles and correlation of drug release in vivo based on FRET mechanism

This study introduces a live imaging technique for real-time, non-invasive monitoring of drug release from long-acting microneedles using FRET (Fluorescence Resonance Energy Transfer). Employing Cy5.5 and Cy7 as FRET pairs and levonorgestrel as the model drug, we fabricated microneedles with varying PLGA molecular weights, demonstrating distinct release profiles. The FRET-PLGA-10-MN demonstrated a rapid drug release profile, reaching nearly complete release within a two-day period, while FRET-PLGA-30-MN showed a sustained release over four days. Sensitized Emission FRET (SE-FRET) optimized the imaging process, providing a robust correlation between FRET signals and drug absorption. This method surpasses traditional pharmacokinetic studies by offering a more efficient and comprehensive analysis of microneedle release dynamics in vivo, paving the way for enhanced long-acting microneedle design and therapeutic outcomes. Statement of significance1. FRET technology was applied to microneedle drug delivery system for the first time, which realized real-time, quantitative and non-invasive monitoring of drug release process.2. The long-term microneedle technique was combined with sensitized emission method, and the FRET remaining ratio was innovatively used to investigate the FRET characteristics of microneedles, and the fluorescence ratio of FRET and donor double-channel was quantitatively calculated.3. The correlation between visual fluorescence images of FRET effect and semi-quantitative calculation results based on fluorescence intensity and drug release in vivo with drug-loaded microneedles was analyzed.

Development of a Controllable Intelligent Drug Delivery System for Efficient Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a complex inflammatory disease of the joints, which is often accompanied by degeneration of articular cartilage and bone erosion, seriously affecting the quality of life and psychological state of patients. RA is difficult to be cured completely, and currently the main purpose of relief is through the use of anti-inflammatory and antirheumatic drugs, hormones, and biological agents. Tofacitib is a new type of small molecule inhibitor, which has a good effect in the treatment of RA. The current direct drug delivery method has serious side effects caused by the systemic distribution of the drug, so there is a need to develop an intelligent drug delivery system to realize precise treatment. In this work, tofacitib, gallic acid, targeted molecule folic acid, and Fe(III) were selected to assemble a novel type of artificial controllable nanodrug GF-TF. The self-photoacoustic/magnetic resonance imaging (self-PA/MRI) monitored the enrichment of GF-TF in the lesion in real-time, and artificially regulated the addition of deferoxamine (DFO) at the optimal enrichment. DFO strongly chelates Fe(III) in GF-TF and causes its structure to disintegrate gradually, and the self-PA/MRI signal of GF-TF became weaker while tofacitib began to be released, thus realizing the precise and artificially controlled release of the drug under the guidance of imaging. This nanodrug not only achieves efficient aggregation of drugs in inflamed joints, but also achieves real-time monitoring and precise control of drug release through self-PA/MRI, providing a new strategy for the precise treatment of RA.

Ocular pharmacokinetics of acetazolamide from intravitreal implants by high-performance liquid chromatography coupled to tandem mass spectrometry

Glaucoma, a leading cause of irreversible blindness, affects about 70 million people globally. Its treatment focuses on reducing intraocular pressure. Acetazolamide, a potent anti-glaucoma drug, is currently used only systemically due to low solubility and permeation, which cause severe side effects. Developing topical medications with acetazolamide requires robust analytical methods for its detection in biological samples. In this context, this study aimed to develop a method to quantify acetazolamide in rabbit vitreous humor samples. The method involved a simple, fast, inexpensive, and environmentally friendly protein precipitation step for sample preparation, needing just 50 μL of sample and 200 μL of organic solvent, with adequate recovery. This was combined with high-performance liquid chromatography coupled to tandem mass spectrometry, enabling highly sensitive (LOQ of 5 ng/mL) quantification within only 5 min. The method proved to be selective, precise, and accurate, with well-fitted analytical curves, with no carryover, and no matrix effect impacting reliability. The method was successfully applied to analyze vitreous humor samples from rabbits in pharmacokinetic studies, monitoring drug release from intravitreal implants. Results showed a controlled release profile, with a maximum drug concentration (Cmax) of 426.01 ± 64.57 ng/mL, time to reach Cmax (Tmax) of 28 days, and area under the curve (AUC0–42 and AUC0-∞) of 7722.66 ± 1125.96 ng days/mL and 8998.11 ± 1311.92 ng days/mL, respectively. The device demonstrated significantly slower elimination, ensuring therapeutic levels for an extended period when compared to intravitreal injection.

Self-Indicating Polymer Prodrug Nanoparticles for pH-Responsive Drug Delivery in Cancer Cells and Real-Time Monitoring of Drug Release.

Amphiphilic self-indicating and responsive polymer-based prodrugs have generated much interest as potential stimuli-responsive intelligent drug delivery systems (DDS) due to their ability to selectively deliver drugs to the cancer cells and to monitor real-time cellular uptake of the drug by imaging technique(s). In this direction, we have synthesized a new pH-responsive N-vinyl-2-pyrrolidone and coumarin-based fluorescent self-indicating polymeric prodrug (SIPD), poly(NVP)-b-poly(FPA.DOX-r-FPA-r-CA). This block copolymer prodrug self-assembled into stable micellar nanoparticles under physiological conditions that reduced undesirable drug leakage to normal cells but resulted in the release of the anticancer drug doxorubicin (DOX) in cancer cells because of acidic pH-induced cleavage of imine bonds between DOX and the copolymer. While the polymer was found to be highly biocompatible with both normal (HEK-293) cells and cancer (MCF-7) cells even at high concentrations by MTT assay, the polymer prodrug nanoparticles showed toxicity even higher than that of free DOX in cancer cells. Phase contrast microscopy also depicted the cytotoxic effects of the nanoparticles on cancer cells. The coumarin units present in the polymer served as a fluorescence resonance energy transfer (FRET) pair with the covalently attached DOX molecules, which was established by steady-state and time-resolved fluorescence spectroscopy. Furthermore, confocal microscopy results confirmed the FRET phenomenon, as the fluorescence intensity of coumarin in the micellar nanoparticles remained quenched initially in MCF-7 cells but recovered with time as the DOX molecules were released and gradually shifted toward the targeted nucleus. All of these studies implied that the synthesized prodrug nanoparticles may provide another viable option for delivering chemotherapeutic drugs into cancer cells with a capability of real-time monitoring of drug release.

Quantification of Microsphere Drug Release by Fluorescence Imaging with the FRET System.

Accurately measuring drug and its release kinetics in both in vitro and in vivo environments is crucial for enhancing therapeutic effectiveness while minimizing potential side effects. Nevertheless, the real-time visualization of drug release from microspheres to monitor potential overdoses remains a challenge. The primary objective of this investigation was to employ fluorescence imaging for the real-time monitoring of drug release from microspheres in vitro, thereby simplifying the laborious analysis associated with the detection of drug release. Two distinct varieties of microspheres were fabricated, each encapsulating different drugs within PLGA polymers. Cy5 was selected as the donor, and Cy7 was selected as the acceptor for visualization and quantification of the facilitated microsphere drug release through the application of the fluorescence resonance energy transfer (FRET) principle. The findings from the in vitro experiments indicate a correlation between the FRET fluorescence alterations and the drug release profiles of the microspheres.

Rapid Synthesis of Functions-Integrated Hydrogel as a Self-Powered Wound Dressing for Real-Time Drug Release and Health Monitoring.

A bio-hydrogel is prepared via a low-cost and time-saving strategy and is studied as a self-powered wound dressing for precision medicine and health monitoring. Promoted by a dual self-catalytic pair composed of Fe3+ and catechol, gelation time is dramatically accelerated to 15s and the hydrogel can be freely modeled at -18°C without losing flexibility. As smart wound dressing, the required properties such as self-healing, self-adhesion, antibacterial, and sensing stability, are integrated into one hydrogel. TA@CNC offers abundant hydrogen bond and metal-ligand coordination which facilitate the hydrogel with a self-healing efficiency of 91.6%. Owing to the catechol in TA@CNC, hydrogel can adhere to multiple substrates including skin, and show good antibacterial activity. Inspired by a fruit battery, a self-powered wound dressing is fabricated, which exhibits excellent correlation and efficiency in real-time monitoring of body activity and drug release. In vivo experiments prove that efficient drug release of hydrogel dressing significantly accelerate wound healing. Additionally, the dressing exhibits excellent biocompatibility and has no negative impacts on organs. Herein, a smart wound dressing that is different from the traditional way is proposed. As a self-powered device, it can be integrated with wireless devices and is expected to participate in promising applications.

Polymer Nanoparticles for Preferential Delivery of Drugs Only by Exploiting the Slightly Elevated Temperature of Cancer Cells and Real-Time Monitoring of Drug Release.

Rapid proliferation and a faster rate of glycolysis in cancer cells often result in an elevated local temperature (40-43 °C) at the tumor site. Nanoparticles prepared from polymers with two lower critical solution temperatures (LCSTs) can be utilized to take advantage of this subtle temperature elevation to deliver anticancer drugs preferably to the cancer cells, thereby enhancing the overall therapeutic efficacy and reducing side effects. In this direction, we synthesized N-vinyl-2-pyrrolidone (NVP) and substituted NVP (sub-NVP: C2-NVP, C4-NVP)-based polymers with precisely controlled LCSTs by varying the ratio of NVP and sub-NVP. The first LCST (LCST1) was kept below 37 °C to promote self-assembly, drug loading, and structural stability in physiological conditions and the second LCST (LCST2) was in the range of 40-43 °C to ensure mild hyperthermia-induced drug release. Additionally, covalent attachment of tetraphenylethylene (TPE, AIEgen) resulted in aggregation-induced emission in thermoresponsive micellar nanoparticles in which TPE acted as a Förster Resonance Energy Transfer (FRET) pair with the loaded anticancer drug doxorubicin (DOX). Tracking of FRET-induced fluorescence recovery of TPE molecules was utilized to confirm the real-time thermoresponsive release of DOX from nanoparticles and eventual localization of TPE in the cytoplasm and DOX in the nucleus. In vitro cellular studies such as cytotoxicity, cellular uptake, and thermoresponsive drug release showed that the DOX-loaded polymeric nanoparticles were nontoxic to normal cells (HEK-293) but significantly more effective in cancer cells (MCF-7) at 40 °C. To our knowledge, this is the first report of preferential delivery of anticancer drugs only by exploiting the slightly elevated temperature of cancer cells.

A Novel Fluorescent Gemcitabine Prodrug That Follows a Nucleoside Transporter-Independent Internalization and Bears Enhanced Therapeutic Efficacy With Respect to Gemcitabine.

The multiplexity of cancer has rendered it the second leading cause of mortality worldwide and theragnostic prodrugs have gained popularity in recent years as a means of treatment. Theragnostic prodrugs enable the simultaneous diagnosis and therapy of tumors via high-precision real-time drug release monitoring. Herein, we report the development of the small theragnostic prodrug GF, based on the nucleoside anticancer agent gemcitabine and the fluorescent dye 5(6)-carboxyfluorescein. We have successfully demonstrated its efficient internalization in tumor cells, showing localization throughout both the early and late endocytic pathways. Its mechanism of cell internalization was evaluated, confirming its independence from nucleoside transporters. Its cellular localization via confocal microscopy revealed a clathrin-mediated endocytosis mechanism, distinguishing it from analogous compounds studied previously. Furthermore, GF exhibited stability across various pH values and in human blood plasma. Subsequently, its in vitro cytotoxicity was assessed in three human cancer cell lines (A549, U87 and T98). Additionally, its pharmacokinetic profile in mice was investigated and the consequent drug release was monitored. Finally, its in vivo visualization was accomplished in zebrafish xenotransplantation models and its in vivo efficacy was evaluated in A549 xenografts. The results unveiled an intriguing efficacy profile, positioning GF as a compelling candidate warranting further investigation.

A self‐reinforced activatable photosensitizer prodrug enabling synergistic photodynamic and chemotherapy

AbstractAs a novel drug development paradigm, selective activation of prodrugs provides the potential for precise tumor chemotherapy, thereby presenting an opportunity for advancing cancer treatment. The combination of photodynamic therapy (PDT) and prodrug can enhance the therapeutic efficacy while simultaneously enabling real‐time monitoring of drug distribution and release. However, the tumor hypoxia microenvironment and the frequent high‐dose administration of prodrugs significantly impede therapeutic efficacy and escalate treatment‐related risks. Herein, a tumor microenvironment‐specific release prodrug is constructed, termed NBS‐2S‐5FU. Under the influence of glutathione (GSH), NBS‐2S‐5FU undergoes activation, leading to the release of photosensitizer NBS and chemotherapeutic agent 5‐FU derivatives. Under irradiation, NBS produces sufficient superoxide radical () while 5‐FU derivatives inhibit DNA biosynthesis, thereby effectively suppressing tumor growth at low doses. Subsequent in vivo studies utilizing NBS‐2S‐5FU liposomes exhibit outstanding anti‐cancer effectiveness. This study highlights a promising direction for advancing combined prodrugs that integrate PDT and chemotherapy.

Recent Progress of Multifunctional Molecular Probes for Triple-Negative Breast Cancer Theranostics.

Breast cancer (BC) poses a significant threat to women's health, with triple-negative breast cancer (TNBC) representing one of the most challenging and aggressive subtypes due to the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Traditional TNBC treatments often encounter issues such as low drug efficiency, limited tumor enrichment, and substantial side effects. Therefore, it is crucial to explore novel diagnostic and treatment systems for TNBC. Multifunctional molecular probes (MMPs), which integrate target recognition as well as diagnostic and therapeutic functions, introduce advanced molecular tools for TNBC theranostics. Using an MMP system, molecular drugs can be precisely delivered to the tumor site through a targeted ligand. Real-time dynamic monitoring of drug release achieved using imaging technology allows for the evaluation of drug enrichment at the tumor site. This approach enables accurate drug release, thereby improving the therapeutic effect. Therefore, this review summarizes the recent advancements in MMPs for TNBC theranostics, encompassing the design and synthesis of MMPs as well as their applications in the field of TNBC theranostics.

PH and temperature dual-responsive hollow mesoporous silica nanoparticles for drug encapsulation and delivery

In this work, pH and temperature dual-responsive drug delivery vehicles (CDs/PNVCL@HMSNs) with 57.05% drug loading efficiency were prepared. Hollow mesoporous silicon nanoparticles (HMSNs) were synthesized by selective etching. The mixed shells on the surface of HMSNs were composed of carbon dots (CDs) and poly (N-vinylcaprolactam) (PNVCL), which were linked to HMSNs via Schiff base reaction. At room environment (pH = 7.4, T = 25 °C), PNVCL was stretched, so that the model drug Doxorubicin (DOX) could be transported freely through the mesopores. In the blood stream (pH = 7.4, T = 37 °C), PNVCL was collapsed, and DOX was encapsulated to form PNVCL@HMSNs-DOX. CDs were grafted to give CDs/PNVCL@HMSNs-DOX and could further inhibit the leakage of drugs. At the acidic environment of the tumor site, Schiff base bonds broke, leading to shell shedding and DOX release. The drug release could be real-time monitored by the change in fluorescence intensity, which was confirmed by the linear fitting of the fluorescence strength of CDs and the percentage of DOX released. CDs/PNVCL@HMSNs are intriguing drug delivery systems (DDSs), which can combine real-time monitoring and control of drug release.

Plasmonic nano-bowls for monitoring intra-membrane changes in liposomes, and DNA-based nanocarriers in suspension.

Programmable nanoscale carriers, such as liposomes and DNA, are readily being explored for personalized medicine or disease prediction and diagnostics. The characterization of these nanocarriers is limited and challenging due to their complex chemical composition. Here, we demonstrate the utilization of surface-enhanced Raman spectroscopy (SERS), which provides a unique molecular fingerprint of the analytes while reducing the detection limit. In this paper, we utilize a silver coated nano-bowl shaped polydimethylsiloxane (PDMS) SERS substrate. The utilization of nano-bowl surface topology enabled the passive trapping of particles by reducing mobility, which results in reproducible SERS signal enhancement. The biological nanoparticles' dwell time in the nano-trap was in the order of minutes, thus allowing SERS spectra to remain in their natural aqueous medium without the need for drying. First, the geometry of the nano-traps was designed considering nanosized bioparticles of 50-150 nm diameter. Further, the systematic investigation of maximum SERS activity was performed using rhodamine 6 G as a probe molecule. The potential of the optimized SERS nano-bowl is shown through distinct spectral features following surface- (polyethylene glycol) and bilayer- (cholesterol) modification of empty liposomes of around 140 nm diameter. Apart from liposomes, the characterization of the highly crosslinked DNA specimens of only 60 nm in diameter was performed. The modification of DNA gel by liposome coating exhibited unique signatures for nitrogenous bases, sugar, and phosphate groups. Further, the unique sensitivity of the proposed SERS substrate displayed distinct spectral signatures for DNA micelles and drug-loaded DNA micelles, carrying valuable information to monitor drug release. In conclusion, the findings of the spectral signatures of a wide range of molecular complexes and chemical morphology of intra-membranes in their natural state highlight the possibilities of using SERS as a sensitive and instantaneous characterization alternative.

Visualization and Quantification of Drug Release by GSH-Responsive Multimodal Integrated Micelles.

Using molecular imaging techniques to monitor biomarkers and drug release profiles simultaneously is highly advantageous for cancer diagnosis and treatment. However, achieving the accurate quantification of both biomarkers and drug release with a single imaging modality is challenging. This study presents the development of a glutathione (GSH)-responsive polymer-based micelle, PEG-SS-FCy7/PEG-SS-GEM (PSFG), which can precisely localize the tumor using bimodal imaging and prevent drug leakage. These PSFG micelles exhibit a small particle size of 106.3 ± 12.7 nm with a uniform size distribution, and the drug loading efficiency can also be easily controlled by changing the PEG-SS-FCy7 (PSF) and PEG-SS-GEM (PSG) feeding ratio. The PSFG micelles display weak fluorescence emission and minimal drug release under physiological conditions but collapse in the presence of GSH to trigger near-infrared fluorescence and the 19F magnetic resonance imaging signal, allowing for real-time monitoring of intracellular GSH levels and drug release. GSH could synergistically promote the disassembly of the micellar structure, resulting in accelerated probe and drug release of up to about 93.1% after 24 h. These prodrug micelles exhibit high in vitro and in vivo antitumor abilities with minimal side effects. The GSH-responsive drug delivery system with dual-modal imaging capability provides a promising imaging-guided chemotherapeutic platform to probe the tumor microenvironment and quantify real-time drug release profiles with minimal side effects.

A pH/Redox Dual‐Responsive Nanocarrier for Hypoxia‐Activated Prodrug and Anticancer Prodrug in Cancer Treatment

AbstractTumor microenvironment heterogeneity (TMH) remains a challenge in cancer treatment. Nanocarrier prodrugs based on small‐molecular drug or macromolecular drug conjugates emerge as an efficient approach for multidrug delivery at tumor sites and activating the prodrugs by endogenous stimuli resulting from TMH. Herein, a redox/pH dual‐sensitive micelle conjugated is developed via disulfide linkage with naphthalimide‐based prodrug (PNA), assigned as PDM to encapsulate hypoxia‐activated prodrug, banoxantrone (AQ4N), for combination therapy. These micelles have several interesting features, including sufficiently stable with less drug release under physiological conditions and dual stimuli‐triggered intracellular release, high drug loading content, and negligible cytotoxicity. More importantly, in vitro cytotoxicity of AQ4N‐loaded PDM micelles exhibits a combinational anticancer efficacy between chemotherapy of PNA and hypoxia‐activated chemotherapy of AQ4N under hypoxic conditions. Moreover, the developed PNA as a new chemotherapeutic drug displays good therapeutic efficiency and fluorescent properties, which can be used for monitoring drug release in real time. This study not only offers an attractive strategy for an effective combination of traditional chemotherapy and hypoxia‐activated chemotherapy, but also provides an important concept to develop dual stimuli‐sensitive prodrug nanoplatform targeting for endogenous TMH.

Construction and evaluation of a nanosystem that combines acidification promoted chemodynamic therapy and intracellular drug release monitoring

Triple-negative breast cancer (TNBC) is a highly invasive subtype of breast cancer that seriously affects women’s physical and mental health. Chemodynamic therapy (CDT) induces cell death by specifically generating Fenton/Fenton-like reactions within tumor cells. However, the weak acidity of the tumor microenvironment (TME) greatly weakens the effectiveness of CDT. This work constructed a kind of P-CAIDF/PT nanoparticles (NPs), composed of two Pluronic F127 (PF127) based polymers: one was PF127-CAI (P-CAI), composed by connecting PF127 with the carbonic anhydrase IX (CA IX) inhibitor (CAI); the other was PF127-SS-TPE (PT), composed of PF127 and the aggregation-induced emission molecule, tetraphenylethylene (TPE), via the linkage of disulfide bonds. The two polymers were employed to construct the doxorubicin (DOX) and ferrocene (Fc) co-loaded P-CAIDF/PT NPs through the film dispersion method. After being administrated via i.v., P-CAIDF/PT could be accumulated in the TME by the enhanced permeability and retention (EPR) effect and engulfed by tumor cells. P-CAI induced intracellular acidification by inhibiting the overexpressed CA IX, thus promoting CDT by enhancing the Fc-mediated Fenton reaction. The acidification-enhanced CDT combined with the DOX-mediated chemotherapy could improve the therapeutic effect on TNBC. Moreover, P-CAIDF/PT also monitored the intracellular drug release processes through the fluorescence resonance energy transfer (FRET) effect depending on the inherent DOX/TPE pair. In conclusion, the P-CAIDF/PT nanosystem can achieve the combination therapy of acidification-enhanced CDT and chemotherapy as well as therapy monitoring, thus providing new ideas for the design and development of TNBC therapeutic agents.

Photoinduced Electron Transfer-Based Glutathione-Sensing Theranostic Nanoprodrug with Self-Tracking and Real-Time Drug Release Monitoring for Cancer Treatment.

The rapid development of nanomedicine has considerably advanced precision therapy for cancer treatment. Superior to traditional chemotherapy, emerging theranostic nanoprodrugs can effectively realize inherent self-tracking, targeted drug delivery, stimuli-triggered drug release, and reduced systemic toxicity of chemotherapeutic drugs. However, theranostic nanoprodrugs with real-time drug release monitoring have remained rare so far. In this work, we developed a new glutathione-responsive theranostic nanoprodrug with a high drug-loading content of 59.4 wt % and an average nanoscale size of 46 nm, consisting of the anticancer drug paclitaxel and a fluorescent imaging probe with a high fluorescence quantum yield, which are linked by a disulfide-based glutathione-sensitive self-immolating linker. The strong fluorescence emission of the fluorophore enables efficacious self-tracking and sensitive fluorescence "ON-OFF" glutathione sensing. Upon encountering high-level glutathione in cancer cells, the disulfide bond is cleaved, and the resulting linker halves spontaneously collapse into cyclic small molecules at the same pace, leading to the simultaneous release of the therapeutic drug and the fluorescence-OFF imaging probe. Thereby, the drug release process is efficiently monitored by the fluorescence change in the nanoprodrug. The nanoprodrugs exerted high cytotoxicity toward various cancer cells, especially for A549 and HEK-293 cells, in which the nanoprodrugs generated better therapeutic effects than free paclitaxel. Our work demonstrated a new modality of smart theranostic nanoprodrugs for precise cancer therapy.

Biosensors Precision in Healthcare: A Scientific Odyssey

Biosensors have been the beacon of precision in the ever-evolving landscape of health care and offer a profound impact on diagnostics and patient care. These devices are designed to detect specific biological markers and convert then into measurable signals, seamlessly blending biology with cutting-edge technology. The diverse tapestry of biosensors encompass enzyme based sensors, immuno-assays, photo-biosensors, tissue-based sensors, DNA biosensors and nano-biosensors. Enzyme-based biosensors showcase unparalleled catalytic precision exemplified by glucose biosensors. Glucose oxidase serves as the biological catalyst and converts glucose into gluconic acid and hydrogen peroxide. Electrodes of the sensor then transduce this reaction into measurable signals which enables the precise quantification of glucose levels in diabetes management. Similarly, immunoassays rely on the specificity of antigen-antibody interactions. Most widely used immunoassay, Enzyme-linked immunosorbent assay (ELISA) exemplify this category, which finds applications in a number of diagnostics and provide a window into immunological responses and diseases such as HIV. Advancing the field of biosensing are the photobiosensors which utilize diverse technologies such as fluorescence resonance energy transfer (FRET) to illuminate biological processes. Genetically encoded biosensors that employ proteins like green fluorescent protein (GFP), enable non-invasive monitoring of cellular dynamics and offer real-time insights. Another cateogory, tissue-based biosensors converge the technology with the physiological environments. For instance, implantable glucose sensors that continuously monitor blood glucose concentrations and provide real-time data for personalized treatment approaches. At the core of precision diagnostics lie DNA biosensors such as DNA microarrays. They offer parallel analysis of gen expression, influencing decisions in cancer diagnostics and pharmacogenomics. Nanobiosensors, represented by nanoparticle-based sensors, navigate the nano-frontiers with exceptional sensitivity. For example, quantum dots exhibit unique optical properties for sensitive detection. Likewise, gold nanoparticles based biosensors enable real-time monitoring of drug release in drug delivery systems and emphasize their role in precision medicine. As biosensors advance, ethical considerations come to the forefront. Issues such as data privacy, consent, and equitable access to these technologies demand careful attention. It becomes imperative to ensure that biosensors are developed and deployed responsibly with a keen awareness of potential societal implications in navigating the ethical landscape. In the symphony of precision that biosensors bring to healthcare, their types and applications reflect not only technological prowess but also the ethical responsibility inherent in their development and deployment. As these devices continue to evolve, the healthcare landscape stands on the brink of a new era, where precision and ethics intertwine for the betterment of patient outcomes.

Preclinical Application of CEST MRI to Detect Early and Regional Tumor Response to Local Brain Tumor Treatment.

Treating glioblastoma and monitoring treatment response non-invasively remain challenging. Here, we developed a robust approach using a drug-loaded liposomal hydrogel that is mechanically compatible with the brain, and, simultaneously, we successfully monitored early tumor response using Chemical Exchange Saturation Transfer (CEST) MRI. This CEST-detectable liposomal hydrogel was optimized based on a sustainable drug release and a soft hydrogel for the brain tumor, which is unfavorable for tumor cell proliferation. After injecting the hydrogel next to the tumor, three distinctive CEST contrasts enabled the monitoring of tumor response and drug release longitudinally at 3T. As a result, a continuous tumor volume decrease was observed in the treatment group along with a significant decrease in CEST contrasts relating to the tumor response at 3.5 ppm (Amide Proton Transfer; APT) and at -3.5 ppm (relayed Nuclear Overhauser Effect; rNOE) when compared to the control group (p < 0.05). Interestingly, the molecular change at 3.5 ppm on day 3 (p < 0.05) was found to be prior to the significant decrease in tumor volume on day 5. An APT signal also showed a strong correlation with the number of proliferating cells in the tumors. This demonstrated that APT detected a distinctive decrease in mobile proteins and peptides in tumors before the change in tumor morphology. Moreover, the APT signal showed a regional response to the treatment, associated with proliferating and apoptotic cells, which allowed an in-depth evaluation and prediction of the tumor treatment response. This newly developed liposomal hydrogel allows image-guided brain tumor treatment to address clinical needs using CEST MRI.