Targeted Drug Release Research Articles

Liposome-encapsulated bacteriochlorin: tumor cell inactivation using photodynamic therapy.

Photodynamic Therapy (PDT) employs light and non-toxic components, including a photosensitizer (PS) and oxygen, to induce cellular effects and target cancer cells. Bacteriochlorin (Bch), a PS absorbing longer wavelengths, offers deeper tissue penetration, broadening PDT's therapeutic reach. A liposomal formulation (LF) was developed to improve solubility, stability, bioavailability, and enable controlled, targeted drug release to enhance Bch's effectiveness. The present study aims to describe a new third generation of low-cost Bch, reducing the required dose for cancer cell death. Researchers compared the photodynamic activity of Bch in its free form and as an LF, evaluating its efficiency and therapeutic potential in vitro. Bch was obtained from bacterial precursors via extraction and transesterification. LF was produced using the film hydration method, a low-cost method without the need for expensive equipment. Absorbance and cell viability (MTT assay) data were analyzed statistically (ANOVA and Tukey test, 95% confidence interval). Results showed LF significantly outperformed free Bch in all tested cell lines. LF exhibited 140 times higher potency in MIA PaCa-2 cells (IC50 = 6 nM) and 22 times higher potency in MRC-5 cells (IC50 = 3 nM) compared to free Bch. Furthermore, the presence of LF led to the protection of Bch from photodegradation, thereby enhancing its performance. In conclusion, PDT using liposomal Bch demonstrated superior efficiency, low systemic toxicity, and no drug resistance, reinforcing its clinical potential.

Development of Satranidazole HCl-Loaded Oral Nanoparticulate Formulation for Colon Targeting and Colon Cancer Therapy Associated with Inflammatory Bowel Disease.

Colon-targeted drug delivery is a crucial area of research aimed at treating local disorders like IBD, including ulcerative colitis and Crohn's disease. By delivering drugs directly to the colon, this approach enhances therapeutic efficacy and minimizes systemic toxicity. Nanoparticles are an effective vehicle for controlled drug delivery, improving treatment outcomes for colon-specific diseases. The study aimed to develop an oral nanoparticulate formulation of Satranidazole (STZ) using a solvent evaporation technique for colonic targeting and characterize its physicochemical properties, compatibility, and in vitro drug release profile. Using a modified solvent evaporation method, STZ-loaded nanoparticles (STZ-NPs) were formulated using Eudragit RS100 and RL100 polymers. Preformulation studies, including FT-IR and DSC, were performed to confirm the compatibility between the drug and polymers. The nanoparticles were evaluated in terms of entrapment efficiency, particle size, zeta potential, polydispersity index, and in-vitro drug release study. The optimized formulation (F3) demonstrated the highest entrapment efficiency (83.55%) with particle sizes ranging from 107.9 nm to 302 nm and a zeta potential between -34.25 mV and +48.8 mV. In vitro drug release studies showed controlled release over 16 hours, with the optimized batch achieving 95.85% drug release, indicating effective accumulation in the inflamed colon. The Satranidazole-loaded nanoparticles, containing time- and pH-dependent polymers, successfully inhibited premature drug release in acidic environments and provided controlled release at colonic pH. Thus, this delivery system shows promise as an effective treatment for IBD, offering targeted drug release and reduced systemic toxicity.

Multifunctional Janus Hydrogels: Surface Design Strategies for Next-Generation Clinical Solutions

Janus hydrogels, distinguished by their dual-sided structure with distinct physical and chemical properties, have garnered significant attention in the medical field, particularly for applications in drug delivery, tissue engineering, and wound healing. Their ability to simultaneously perform multiple functions, such as targeted drug release and biomimetic tissue interaction, positions them as a promising platform for advanced therapeutic strategies. The growing interest in these hydrogels is primarily driven by their multifunctionality and capacity to address complex biological needs. This review delves into the design, fabrication methods, and applications of Janus hydrogels in medicine, focusing on their potential to overcome the limitations of conventional therapies and providing a comprehensive overview of their role in contemporary biomedical applications.

Emerging Multifunctional Biomaterials for Addressing Drug Resistance in Cancer

Drug resistance remains a major barrier to effective cancer treatment, contributing to poor patient outcomes. Multifunctional biomaterials integrating electrical and catalytic properties offer a transformative strategy to target diverse resistance mechanisms. This review explores their ability to modulate cellular processes, remodel the tumor microenvironment (TME), and enhance drug delivery. Electrically active biomaterials enhance drug uptake and apoptotic sensitivity by altering membrane potentials, ion channels, and intracellular signaling, synergizing with chemotherapy. Catalytic biomaterials generate reactive oxygen species (ROS), activate prodrugs, reprogram hypoxic and acidic TME, and degrade the extracellular matrix (ECM) to improve drug penetration. Hybrid nanomaterials (e.g., conductive hydrogels, electrocatalytic nanoparticles), synergize electrical and catalytic properties for localized, stimuli-responsive therapy and targeted drug release, minimizing systemic toxicity. Despite challenges in biocompatibility and scalability, future integration with immunotherapy, personalized medicine, and intelligent self-adaptive systems capable of real-time tumor response promises to accelerate clinical translation. The development of these adaptive biomaterials, alongside advancements in nanotechnology and AI-driven platforms, represents the next frontier in precision oncology. This review highlights the potential of multifunctional biomaterials to revolutionize cancer therapy by addressing multidrug resistance at cellular, genetic, and microenvironmental levels, offering a roadmap to improve therapeutic outcomes and reshape oncology practice.

Pirfenidone encapsulated in succinylated gelatin-coated liposomes exhibits sustained antifibrotic effects in in vitro models of renal, pulmonary, and hepatic fibrosis.

Pirfenidone encapsulated in succinylated gelatin-coated liposomes exhibits sustained antifibrotic effects in in vitro models of renal, pulmonary, and hepatic fibrosis.

Biofunctional Excipients: Their Emerging Role in Overcoming the Inherent Poor Biopharmaceutical Characteristics of Drugs

Background/Objectives: With advancements in biomaterial sciences, biofunctional excipients have emerged to focus on solving issues with the drugs’ inherent biopharmaceutical characteristics such as poor solubility, permeability, in vivo dissolution, and effective targeting. These advanced excipients significantly impact drug solubility, dissolution rates, absorption rates, permeation rates, penetration ability, targeting ability, and pharmacokinetic profiles. Methods: A literature review of recently published articles was prepared. Data were collected using scientific search engines. This review provided a detailed discussion of various biofunctional excipients including smart polymers, targeted polymers, bioadhesive polymers, lipids, amino acids, cyclodextrins, and biosurfactants. Each category was discussed in detail concerning its biofunctional applications, the mechanisms underlying these biofunctions, and examples of their effects on drug performance. Results: The data obtained indicated that the rapid advances in the manufacturing of pharmaceutical excipients have resulted in the development of a diverse array of smart or intelligent excipients that play a crucial role in enhancing inherent poor biopharmaceutical characteristics. Conclusion: These advancements have also facilitated the development of various drug delivery systems, including immediate, controlled, sustained, and targeted drug release systems. Also, numerous nano-based delivery systems have emerged utilizing the newly produced excipients.

Nanoscale Investigation of Elasticity Changes and Augmented Rigidity of Block Copolymer Micelles Induced by Reversible Core-Cross-Linking.

Drug-delivery systems have attracted considerable attention due to their potential to increase the bioavailability of certain drugs and mitigate side effects by enabling targeted drug release. Reversibly core-cross-linked block copolymer micelles providing a hydrophilic and potentially nonimmunogenic shell and a hydrophobic core suitable for the uptake of hydrophobic drugs are frequently considered because of their high stability against environmental changes and dilution. Ultimately, triggering core-de-cross-linking enables the implementation of strategies for targeted drug release, which requests insights into the impact of varying nanomechanical properties on the stability of individual micelles. Here, atomic force microscopy nanoindentation in aqueous media is applied to intact α-allyl-PEG80-b-P(tBGE52-co-FGE12) micelles to quantify changes in their nanomechanical properties induced by dithiobismaleimidoethane (DTME)-mediated Diels-Alder cross-linking of furfuryl moieties and sequential de-cross-linking by reduction of its disulfide bond by tris(2-carboxyethyl)phosphine. As a result of crosslinking by DTME, the apparent Young's modulus of the micelles roughly doubles to 1.18 GPa. Changes to the Young's modulus can be largely reversed by de-cross-linking. Cross-linked and de-cross-linked micelles maintain their structural integrity even in diluted aqueous media below the critical micelle concentration, in contrast to the micelles prior to crosslinking. Understanding the structure-property relationships associated with the observed augmented mechanical stability in native environments is crucial for improving the efficiency of drug encapsulation and introducing refined temporal and spatially controlled drug-release mechanisms.

Applications of Matrix Metalloproteinase-9-Related Nanomedicines in Tumors and Vascular Diseases.

Matrix metalloproteinase-9 (MMP-9) is implicated in tumor progression and vascular diseases, contributing to angiogenesis, metastasis, and extracellular matrix degradation. This review comprehensively examines the relationship between MMP-9 and these pathologies, exploring the underlying molecular mechanisms and signaling pathways involved. Specifically, we discuss the contribution of MMP-9 to tumor epithelial-mesenchymal transition, angiogenesis, and metastasis, as well as its involvement in a spectrum of vascular diseases, including macrovascular, cerebrovascular, and ocular vascular diseases. This review focuses on recent advances in MMP-9-targeted nanomedicine strategies, highlighting the design and application of responsive nanoparticles for enhanced drug delivery. These nanotherapeutic strategies leverage MMP-9 overexpression to achieve targeted drug release, improved tumor penetration, and reduced systemic toxicity. We explore various nanoparticle platforms, such as liposomes and polymer nanoparticles, and discuss their mechanisms of action, including degradation, drug release, and targeting specificity. Finally, we address the challenges posed by the heterogeneity of MMP-9 expression and their implications for personalized therapies. Ultimately, this review underscores the diagnostic and therapeutic potential of MMP-9-targeted nanomedicines against tumors and vascular diseases.

ROS-Responsive Fluorinated Oxalate Nanomedicine for Dual Chemiluminescence/1⁹F MRI Imaging and Targeted Drug Release.

In this study, we developed a novel theranostic nanomedicine formulation that integrates multimodal imaging with controlled drug release in reactive oxygen species (ROS)-rich microenvironments. A fluorinated oxalate compound (FOC) was synthesized through a one-step condensation reaction between 1,1,1,3,3,3-hexafluoro-2-propanol and oxalyl chloride, characterized by 1H, 13C, and 1⁹F NMR spectroscopy. The FOC and luminophore-incorporated nanomedicine formulations reacted rapidly with hydrogen peroxide via the peroxyoxalate chemiluminescence (POCL) mechanism, producing strong chemiluminescence and inducing a notable 19-fold increase in ratiometric 1⁹F NMR signal upon conversion to fluorinated alcohol (FAH), demonstrating promising potential for high-contrast 1⁹F MRI in deep tissue. Following ROS stimulation, the chemical conversion from hydrophobic FOC to hydrophilic FAH led to the degradation of the nanomedicines, facilitating payload release. In vitro experiments with A-431 cancer cells under hypoxic conditions confirmed ROS-responsive drug release, evidenced by enhanced fluorescence from model luminophores. Additionally, doxorubicin-loaded FOC nanomedicines reduced cell viability to 32% under hypoxia while remaining non-toxic in normoxic conditions. These results indicate that FOC-based nanomedicine formulations provide a promising platform for combined chemiluminescence and 1⁹F MRI with targeted therapeutic efficacy in ROS-rich inflammatory and cancerous tissues.

Self-Assembled systems for Nose-to-Brain delivery of Temozolamide (TMZ) in brain tumor therapy.

Self-Assembled systems for Nose-to-Brain delivery of Temozolamide (TMZ) in brain tumor therapy.

Carboxymethyl Starch: A Contemporary Paradigm for Anti Cancer Drug Delivery.

Carboxymethyl starch (CMS) represents a significant advancement in addressing the multifaceted challenges of anticancer drug delivery, including poor aqueous solubility, nonspecific biodistribution, and premature drug release. The strategic incorporation of carboxymethyl moiety (-CH2COOH) onto the starch backbone confers a suite of physicochemical properties that markedly enhance its efficacy as a drug carrier. The carboxymethyl groups, with a pKa of approximately 4.5, exhibit pronounced pH-responsiveness, undergoing a transition from a predominantly deprotonated, hydrophilic state at physiological pH (7.4) to a more protonated form in the acidic tumor microenvironment (pH 6.5-6.8) facilitating targeted drug release at neoplastic site. The mucoadhesive attributes ascribable to carboxyl-mucin interactions, prolong gastrointestinal residence time for oral formulations, optimizing drug absorption. Furthermore, these functional groups serve as reactive sites for subsequent modifications, facilitating the development of multifunctional, targeted drug delivery systems with enhanced biocompatibility and minimized off-target effects. The versatility and biocompatibility of CMS position it as a promising platform for next-generation anticancer therapeutics, offering potential for significant advancements in oncological treatment modalities.

Synthesis of heteroatom doped polymer coated nanomaterials for slow and controlled drug release in the physiological microenvironment.

This study aimed to develop doped carbon dots and coat them with carboxyl-polymer to explore their applications in imaging living tissue cells and achieving targeted drug release, particularly for tumor therapy. The synthesis of NP-CDs involved a one-pot hydrothermal reaction of seaweed powder, ethylene diamine, and phosphoric acid at atmospheric pressure. Subsequently, the NP-CDs were coated with carboxyl-mounted PEG to create PEG@NP-CDs, serving as a nano carrier for delivering the anti-cancer drug Doxorubicin (DOX). The drug delivery capabilities of PEG@NP-CDs were assessed, and their sensitivity to variations in pH value was studied. The hydrothermal reaction successfully yielded NP-CDs with distinctive fluorescence properties, exhibiting green fluorescence at 430 nm and varying emission peaks depending on the excitation wavelength used. The subsequent coating of NP-CDs with carboxyl-mounted PEG resulted in PEG@NP-CDs, which demonstrated biocompatibility and potential for drug delivery applications. The MTT assay confirmed the high biocompatibility of PEG@NP-CDs, rendering them suitable for biomedical applications. The study successfully developed a straightforward method to synthesize CDs doped with nitrogen and phosphorus, which exhibited green fluorescence and sensitivity to excitation wavelengths. These nanomaterials have potential for imaging living tissue cells and achieving slow drug release. Their drug delivery capabilities, especially pH sensitivity, make them promising for targeted therapy, particularly in tumors. The biocompatibility of PEG@NP-CDs further supports their safe biomedical use. Overall, PEG@NP-CDs offer a valuable tool for simultaneous imaging and drug delivery, with promising applications in tumor detection and therapy.

Hydrogels and Microgels: Driving Revolutionary Innovations in Targeted Drug Delivery, Strengthening Infection Management, and Advancing Tissue Repair and Regeneration.

Hydrogels and microgels are emerging as pivotal platforms in biomedicine, with significant potential in targeted drug delivery, enhanced infection management, and tissue repair and regeneration. These gels, characterized by their high water content, unique structures, and adaptable mechanical properties, interact seamlessly with biological systems, making them invaluable for controlled and targeted drug release. In the realm of infection management, hydrogels and microgels can incorporate antimicrobial agents, offering robust defenses against bacterial infections. This capability is increasingly important in the fight against antibiotic resistance, providing innovative solutions for infection prevention in wound dressings, surgical implants, and medical devices. Additionally, the biocompatibility and customizable mechanical properties of these gels make them ideal scaffolds for tissue engineering, supporting the growth and repair of damaged tissues. Despite their promising applications, challenges such as ensuring long-term stability, enhancing therapeutic agent loading capacities, and scaling production must be addressed for widespread adoption. This review explores the current advancements, opportunities, and limitations of hydrogels and microgels, highlighting research and technological directions poised to revolutionize treatment strategies through personalized and regenerative approaches.

Innovations in Core-Shell Nanoparticles: Advancing Drug Delivery Solutions and Precision Medicine.

Drug delivery innovation is an important pillar of systems pharmacology wherein nanotechnology offers significant prospects. This expert review examines and unpacks how core-shell nanoparticles (NPs) could revolutionize drug delivery systems and play a key role in advancing personalized and precision medicine. Core-shell NPs have gained attention as flexible tools for drug delivery due to their distinct structure, which features a core material enclosed by a protective shell. This setup offers multiple benefits, such as effective drug encapsulation, shielding the drug from degradation, and allowing for controlled release. Accordingly, the core serves as a safe storage area for the drug while the shell manages the release speed, providing added stability and supporting sustained delivery. By enabling targeted drug release, this controlled mechanism can help improve treatment outcomes and reduce side effects. Various materials, including polymers, lipids, and inorganic substances create these NPs. Biodegradable polymers, such as poly(lactic-co-glycolic acid) and poly(lactic acid), are popular choices because they offer adjustable degradation rates, which further control how the drug is released. These materials can be tailored for better drug loading, compatibility with the host organism, and specific chemical properties to suit different therapeutic needs. Research into core-shell NPs has been advancing in many therapeutic areas, highlighting their potential for drug delivery innovations. The potential of core-shell NPs to revolutionize drug delivery is not just a possibility but a promising reality that could significantly advance the field of personalized/precision medicine.

PH-Dependent Drug Delivery Systems for Ulcerative Colitis Treatment.

Inflammatory bowel diseases (IBDs), such as ulcerative colitis (UC) or Crohn's disease, are becoming a growing global problem due to the limitations of current treatments, which fail to address the needs of patients effectively. UC is characterized by the widespread inflammation of the mucosal lining, affecting both the rectum and the entire length of the colon. Over the past forty years, traditional treatments for IBDs have primarily relied on anti-inflammatory drugs and immunosuppressive medications. Treatment could be more effective if drugs could be specifically targeted to act directly on the colon. Conventional drug delivery systems for IBDs encounter numerous challenges on their way to the colon, such as physiological barriers and disease severity. To address these issues, pH-dependent carriers have emerged as a promising advancement, offering a more effective and tolerable treatment for UC. These carriers enable localized, targeted action, reducing side effects and preventing the premature clearance of drugs from inflamed colon tissues. pH-responsive systems are a leading approach for targeted drug release in colitis treatment as they take advantage of the varying pH levels throughout the gastrointestinal tract (GIT). By incorporating pH-sensitive polymers, they ensure drug protection and controlled release in the lower GIT. This review will discuss the advantages and limitations of pH-dependent drug delivery systems for colon-targeted drug delivery.

Hydrogels and Nanogels: Pioneering the Future of Advanced Drug Delivery Systems.

Conventional drug delivery approaches, including tablets and capsules, often suffer from reduced therapeutic effectiveness, largely attributed to inadequate bioavailability and difficulties in ensuring patient adherence. These challenges have driven the development of advanced drug delivery systems (DDS), with hydrogels and especially nanogels emerging as promising materials to overcome these limitations. Hydrogels, with their biocompatibility, high water content, and stimuli-responsive properties, provide controlled and targeted drug release. This review explores the evolution, properties, and classifications of hydrogels versus nanogels and their applications in drug delivery, detailing synthesis methods, including chemical crosslinking, physical self-assembly, and advanced techniques such as microfluidics and 3D printing. It also examines drug-loading mechanisms (e.g., physical encapsulation and electrostatic interactions) and release strategies (e.g., diffusion, stimuli-responsive, and enzyme-triggered). These gels demonstrate significant advantages in addressing the limitations of traditional DDS, offering improved drug stability, sustained release, and high specificity. Their adaptability extends to various routes of administration, including topical, oral, and injectable forms, while emerging nanogels further enhance therapeutic targeting through nanoscale precision and stimuli responsiveness. Although hydrogels and nanogels have transformative potential in personalized medicine, challenges remain in scalable manufacturing, regulatory approval, and targeted delivery. Future strategies include integrating biosensors for real-time monitoring, developing dual-stimuli-responsive systems, and optimizing surface functionalization for specificity. These advancements aim to establish hydrogels and nanogels as cornerstones of next-generation therapeutic solutions, revolutionizing drug delivery, and paving the way for innovative, patient-centered treatments.

Nose-to-brain Drug Delivery System: An Emerging Approach to Chemotherapy-induced Cognitive Impairment.

The rise in global cancer burden, notably breast cancer, emphasizes the need to address chemotherapy-induced cognitive impairment, also known as chemobrain. Although chemotherapy drugs are effective against cancer, they can trigger cognitive deficits. This has triggered the exploration of preventive strategies and novel therapeutic approaches. Nanomedicine is evolving as a promising tool to be used for the mitigation of chemobrain by overcoming the blood-brain barrier (BBB) with innovative drug delivery systems. Polymer and lipid-based nanoparticles enable targeted drug release, enhancing therapeutic effectiveness. Utilizing the intranasal route of administration may facilitate drug delivery to the central nervous system (CNS) by circumventing first-pass metabolism. Therefore, knowledge of nasal anatomy is critical for optimizing drug delivery via various pathways. Despite challenges, nanoformulations exhibit the potential in enhancing brain drug delivery. Continuous research into formulation techniques and chemobrain mechanisms is vital for developing effective treatments. The intranasal administration of nanoformulations holds promise for improving therapeutic outcomes in chemobrain management. This review offers insights into potential future research directions, such as exploring novel drug combinations, investigating alternative delivery routes, or integrating emerging technologies to enhance the efficacy and safety of nanoformulations for chemobrain management.

Targeted Drug Nanodelivery and Immunotherapy for Combating Tumor Resistance.

Chemotherapy resistance is a common cause of tumor treatment failure. Various molecular responses, such as increased expression of efflux transporter proteins, including Pglycoprotein (P-gp), changes in the tumor microenvironment (TME), the role of platelets, and the effects of cancer stem cells (CSCs), can lead to drug resistance. Through extensive research on the mechanisms of drug resistance, more effective anti-resistance drugs and therapeutic approaches are being developed. This review explores drug resistance mechanisms and summarizes relevant anti-resistance drugs. In addition, due to the therapeutic limitations of the aforementioned treatments, new advances in nanocarrier-based combination immunotherapy to address the challenge of drug resistance have been described. Nanocarriers combined with immunotherapy can not only target tumor sites for targeted drug release but also modulate the autoimmune system and enhance immune efficacy, thereby overcoming tumor drug resistance. This review suggests new strategies for overcoming tumor drug resistance and is expected to inform tumor treatment and prognosis.

Innovative Applications of Bacteria and Their Derivatives in Targeted Tumor Therapy.

Despite significant progress in cancer treatment, traditional therapies still face considerable challenges, including poor targeting, severe toxic side effects, and the development of resistance. Recent advances in biotechnology have revealed the potential of bacteria and their derivatives as drug delivery systems for tumor therapy by leveraging their biological properties. Engineered bacteria, including Escherichia coli, Salmonella, and Listeria monocytogenes, along with their derivatives─outer membrane vesicles (OMVs), bacterial ghosts (BGs), and bacterial spores (BSPs)─can be loaded with a variety of antitumor agents, enabling precise targeting and sustained drug release within the tumor microenvironment (TME). These bacteria and their derivatives possess intrinsic properties that stimulate the immune system, enhancing both innate and adaptive immune responses to further amplify therapeutic effects. The ability of bacteria to naturally accumulate in hypoxic tumor regions and their versatility in genetic modifications allow for tailored drug delivery strategies that synergistically enhance the effectiveness of chemotherapy, immunotherapy, and targeted therapies. This review comprehensively examines the fundamental principles of bacterial therapy, focusing on the strategies employed for bacterial engineering, drug loading, and the use of bacteria and their derivatives in targeted tumor therapy. It also discusses the challenges faced in optimizing bacterial delivery systems, such as safety concerns, unintended immune responses, and scalability for clinical applications. By exploring these aspects, this review provides a theoretical framework for improving bacterial-based drug delivery systems, contributing to the development of more effective and personalized cancer treatments.

Pegylated NIR Fluorophore-Conjugated OBHSA Prodrug for ERα-Targeted Theranostics with Enhanced Imaging and Long-Term Retention.

In recent years, the near-infrared (NIR) fluorescence theranostic system has garnered increasing attention for its advantages in the simultaneous diagnosis- and imaging-guided delivery of therapeutic drugs. However, challenges such as strong background fluorescence signals and rapid metabolism have hindered the achievement of sufficient contrast between tumors and surrounding tissues, limiting the system's applicability. This study aims to integrate the pegylation strategy with a tumor microenvironment-responsive approach. A novel esterase-activated EPR strategy prodrug, OBHSA-PEG-DCM, was designed. This prodrug links OBHSA, a protein degrader capable of efficient ERα protein degradation, to the PEG-modified fluorescent group (dicyanomethylene-4H-pyran, DCM) via an ester bond. This integration facilitates targeted drug delivery and enhances the retention of the fluorescent group within the tumor, allowing distinct in vivo tumor imaging periods. Experimental results show that, benefiting from overexpressed esterase in cancer cells, OBHSA-PEG-DCM can be efficiently hydrolyzed, releasing OBHSA and pegylated DCM. OBHSA demonstrated potent inhibition against MCF-7 cells (IC50 = 1.09 μM). Simultaneously, pegylated DCM exhibited remarkable in vivo imaging capabilities, lasting up to 12 days in mice, due to the enhanced permeability and retention (EPR) effect. OBHSA-PEG-DCM holds promise as a theranostic agent for ERα-positive breast cancer, offering both therapeutic and diagnostic capabilities. Importantly, this study highlights the utility of pegylated NIR fluorophores for long-circulating drug delivery systems, addressing current challenges in achieving high-contrast tumor imaging and effective targeted drug release.