Drug Targeting Research Articles

The antitumor mechanism of glycyrrhetinic acid and its applications in cancer treatment.

Glycyrrhetinic Acid (GA) serves as one of the primary active components of licorice, displaying a range of pharmacological properties, which include anti-inflammatory, antitumor, antiviral, hypoglycemic, and lipid-modulating properties. As the potential of GA in cancer treatment has been thoroughly explored, particularly in applications for liver, lung, and breast cancers, it has garnered widespread attention. According to studies, GA suppresses the growth of cancer cells, triggers autophagy and death, and alters a number of signaling pathways, including ERK, TGF-β/Smad, and PI3K/AKT. Furthermore, the combined use of GA with other drugs (such as doxorubicin and 5-fluorouracil) demonstrates synergistic anticancer effects, enhancing efficacy while reducing adverse reactions. GA is also used in nanoscale drug delivery systems to improve drug targeting and therapeutic outcomes. The molecular processes of GA in cancer therapy are reviewed in this research along with its prospective uses in cancer treatment and synergistic applications with other treatment techniques. To ensure the comprehensiveness and relevance of the studies included, a systematic approach was employed in selecting the studies. The criteria for selection included studies published within the last 10years to ensure the information is up-to-date. Both in vitro and in vivo studies were considered, with a particular emphasis on those that have demonstrated significant mechanistic insights or therapeutic outcomes. In conclusion, the comprehensive review of GA's mechanisms and applications underscores its significant potential as an effective and low-toxicity agent in cancer therapy. Despite the promising findings, future research should focus on addressing the challenges of GA's relatively low bioavailability and exploring its long-term clinical effects. In addition, further investigation into the synergistic potential of GA with emerging therapeutic strategies, such as immunotherapy and gene therapy, is warranted to fully harness its therapeutic benefits and advance cancer treatment options.

Mitochondrial Delivery of Molecular Drugs Bypassing Endocytosis.

Although mitochondria are potential therapeutic target for various diseases, the targeted delivery of drugs to mitochondria is challenging. Conventional carrier-based drug delivery utilizes an endocytic uptake pathway that results in partial and delayed mitochondrial targeting due to complicated endosomal trafficking followed by endosomal escape roots. Here, we report a nonendocytic approach for preferential and rapid mitochondrial delivery of molecular drugs using a designed nanocarrier. The drug-loaded nanocarrier rapidly enters into the cell via temporary membrane pore formation, releases molecular drugs into cytosol without any vesicular entrapment, and labels mitochondria within 5 min. In contrast, control nanocarrier-based delivery of the same molecule via endocytic root leads to lysosomal trafficking. This result demonstrates the advantage of the nonendocytic approach for efficient mitochondrial targeting of drugs with potential therapeutic advantages.

Organometallic Half-Sandwich Complexes of 1,10-Phenanthroline Derivatives with Improved Solubility, Albumin-Binding, and Nanoformulation Potential Targeting Drug Resistance in Cancer.

The development of Rh(III)(η5-C5Me5) and Ru(II)(η6-p-cymene) complexes of 4,7-dichloro-1,10-phenanthroline (DCP) and bathophenanthroline (BP) aims to increase aqueous solubility and potential bioavailability of the lipophilic ligands while also enabling selective activity against multidrug-resistant (MDR) cancer cells. Complexes [M(η6-arene/η5-arenyl)(DCP/BP)Cl]Cl were prepared and characterized by means of nuclear magnetic resonance, infrared, electrospray ionization mass spectrometry, and single crystal X-ray diffraction for [Rh(III)(η5-C5Me5)(DCP)Cl]PF6 and [Ru(II)(η6-p-cymene)(BP)Cl]PF6. The complexes are highly stable in a wide pH range with increased hydrophilicity, and the Rh complexes showed fast and significant binding to human serum albumin (HSA). Cytotoxicity tests were conducted in various breast cancer cells and in cocultured cell lines of the uterine sarcoma parental MES-SA and its MDR counterparts. Both the ligands and their organorhodium complexes displayed a higher cytotoxicity against the MDR MES-SA/Dx5 cells than against the parental cells. As the complex [Rh(III)(η5-C5Me5)(BP)Cl]Cl showed the most promising results (IC50 = 0.23 μM (MES-SA/Dx5) with selectivity ratio 6.7), it was selected for nanoformulation using HSA and also combined with d-α-tocopheryl polyethylene glycol 1000 succinate and poly(lactic-co-glycolic acid). Both composites showed a good encapsulation efficiency and colloidal stability. Based on the in vitro cytotoxicity assays, the use of HSA as a carrier is a promising strategy to enhance the pharmacological properties of the MDR-selective Rh(III)(η5-C5Me5) complexes of 1,10-phenanthroline derivatives.

Abstract A016: A computational chemistry and AI-driven framework for structure-based drug design informed by underlying factors of mutation-induced drug resistance: A study of KRAS

Abstract Mutation-induced drug resistance is a major obstacle in effective cancer treatment. We present a framework that integrates computational chemistry and AI for structure-based drug design targeting drug resistant mutations. To demonstrate the application of our framework, we use Kirsten Rat Sarcoma (KRAS) oncogene as a proof of concept. KRAS is one of the most mutated oncogenes in pancreatic, colorectal, and lung cancers. Mutations in KRAS cause its prolonged activation and excessive cell growth. While the primary mutant KRAS G12C responds to approved covalent inhibitors, several secondary mutations in the binding site (e.g., G12C/Y96C, G12C/Y96S, G12C/Y96D) lead to drug resistance. To understand conformational differences between treatment-sensitive and treatment-resistant populations and to enable structure-based drug design, we conducted molecular dynamics simulations on several drug-free KRAS mutants. Each simulation was performed in triplicate, and trajectory clustering was applied to extract the most populated conformations. Molecular features were calculated for the representative structures. The resulting data were analyzed using three supervised machine learning (ML) models: logistic regression, random forest, and support vector machine. Distinct structural differences in protein dynamics were observed between the two groups, particularly in the switch II binding site region, where covalent inhibitors bind. Variations were detected in residue conformations and the spatial arrangement of molecular features such as hydrogen bond donors and acceptors, as well as aromatic and aliphatic groups. Using ML, we identified that the molecular features of the most populated protein conformations differed significantly between treatment-sensitive and treatment-resistant systems. Notably, solvent exposure and conformational flexibility of residues G10, E62, and H95 within the switch II binding site emerged as the most predictive features of treatment sensitivity, alongside other features such as Lennard-Jones 1-4 energy and backbone mean square displacement. Given these differences, pharmacophores describing the physicochemical and spatial properties of switch II binding site conformations have been extracted for resistant and sensitive systems and will serve as input conditions for generative molecular design. To achieve that, we will utilize existing string- and graph-based generative ML models to design ligands within the binding site of the target. In this approach, the protein binding pocket will be represented by the coordinates of the pharmacophore, guiding the construction of molecular graphs for ligands. Generative ML applied to structure-based drug design will enable the discovery of potential bioactive compounds at an increased rate by accessing vast chemical space. Incorporating protein dynamics into this process provides deeper insights into mutation-induced drug resistance by revealing critical molecular determinants. These insights are essential for guiding the design of selective small molecules against difficult-to-target proteins. Citation Format: Katarzyna Mizgalska, Denis J. Imbody, Eric B. Haura, Wayne C. Guida, Aleksandra Karolak. A computational chemistry and AI-driven framework for structure-based drug design informed by underlying factors of mutation-induced drug resistance: A study of KRAS [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Artificial Intelligence and Machine Learning; 2025 Jul 10-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(13_Suppl):Abstract nr A016.

Carbon Nanotubes as Excellent Adjuvants for Anticancer Therapeutics and Cancer Diagnosis: A Plethora of Laboratory Studies Versus Few Clinical Trials

Encouraging discoveries and excellent advances in the fight against cancer have led to innovative therapies such as photothermal therapy (PTT), photodynamic therapy (PDT), drug targeting (DT), gene therapy (GT), immunotherapy (IT), and therapies that combine these treatments with conventional chemotherapy (CT). Furthermore, 2,041,910 new cancer cases and 618,120 cancer deaths have been estimated in the United States for the year 2025. The low survival rate (<50%) and poor prognosis of several cancers, despite aggressive treatments, are due to therapy-induced secondary tumorigenesis and the emergence of drug resistance. Moreover, serious adverse effects and/or great pain usually arise during treatments and/or in survivors, thus lowering the overall effectiveness of these cures. Although prevention is of paramount importance, novel anticancer approaches are urgently needed to address these issues. In the field of anticancer nanomedicine, carbon nanotubes (CNTs) could be of exceptional help due to their intrinsic, unprecedented features, easy functionalization, and large surface area, allowing excellent drug loading. CNTs can serve as drug carriers and as ingredients to engineer multifunctional platforms associated with diverse treatments for both anticancer therapy and diagnosis. The present review debates the most relevant advancements about the adjuvant role that CNTs could have in cancer diagnosis and therapy if associated with PTT, PDT, DT, GT, CT, and IT. Numerous sensing strategies utilising various CNT-based sensors for cancer diagnosis have been discussed in detail, never forgetting the still not fully clarified toxicological aspects that may derive from their extensive use. The unsolved challenges that still hamper the possible translation of CNT-based material in clinics, including regulatory hurdles, have been discussed to push scientists to focus on the development of advanced synthetic and purification work-up procedures, thus achieving more perfect CNTs for their safer real-life clinical use.

Mining of Targeted Therapeutic Drugs for Hepatocellular Carcinoma based on Programmed Death-related Features and Construction of an Imaging Histology Diagnostic Model.

The programmed cell death (PCD) is crucial in inhibiting cancer cell proliferation and enhancing anti-tumor immune responses. Mining targeted therapeutics for liver hepatocellular carcinoma (LIHC) based on PCD genes and revealing their molecular mechanisms are essential for the development of effective clinical treatments for LIHC. Key genes associated with PCD characteristics of LIHC were identified in cancer genome mapping by the weighted gene co-expression network analysis (WGCNA). In this study, the performance and clinical value of key genes were evaluated by the Receiver operating characteristic curve (ROC). The relative expressions of genes related to PCD in hepatocellular carcinoma were measured employing QRT-PCR. The practical regulation of PCD-correlated key genes on the migration and invasion levels of LIHC cells was assessed by transwell and scratch healing assays. Functional and pathway characterization of gene sets was performed by Gene Set Enrichment Analysis (GSEA). CIBERSORT was used to assess immune cell infiltration in the samples. DSigDB and AutoDock tools were used for molecular docking of key genes and downstream targeted drugs. Impact omics characterization of the samples was determined by the alignment diagram. Three genes, CAMK4, CD200R1, and KCNA3, were screened as key PCD-related genes in LIHC. Cellular experiments verified that CD200R1 promotes migration and invasion levels in hepatocellular carcinoma. GSEA showed that these three genes were enriched for cytokine release, apoptosis, and other pathways. In immune profiling, we revealed that the three genes were related to the infiltration of immune cells such as CD4+ memory T cells and CD8+ T cells. Molecular docking predicted potential drugs for the three biomarkers, among which CAMK4 was tightly bound to GSK1838705A and had the highest AUC in the ROC curve. In addition, we constructed an alignment diagram to accurately assess the imaging features of LIHC. This study provided a new strategy for precision treatment of LIHC by screening key genes associated with PCD in LIHC (CAMK4, CD200R1, and KCNA3), revealing their roles in the regulation of the tumor immune microenvironment and predicting potential target drugs, as well as constructing a diagnostic model based on imaging histology; however, the study did not delve deeper into the long-range drug-target interaction mechanism and lacked molecular dynamics simulation validation, which limited the comprehensiveness of the results. This study identified key genes associated with PCD in LIHC, revealed its immunoregulatory mechanism, and predicted potential target drugs, providing new ideas for precision treatment and diagnosis of hepatocellular carcinoma.

Solid Lipid Nanoparticles: An Innovative Drug Delivery System for Enhanced Bioavailability and Targeted Therapy.

Since the 1990s, solid lipid nanoparticles have been developed as a novel drug delivery system and utilized for delivering various drugs. These nanoparticles can be composed of different solid lipids, such as waxes, fatty acids, and glycerides, which can be stabilized using various surfactants. Solid lipid nanoparticles have attracted considerable interest from researchers due to their innovative and adaptable properties. Furthermore, this delivery strategy offers many benefits over standard colloidal carriers such as polymeric nanoparticles, emulsions, and liposomes. Solid lipid nanoparticles are one of the technologies developed to address challenges related to drug bioavailability and targeting delivery. In this review paper, we have compiled all the essential information concerning solid lipid nanoparticles, including a general introduction, multiple techniques of preparation, and the numerous excipients related to the formulation. Various features of drug inclusion and manufacturing models, as well as their applications, are thoroughly covered. They can improve pharmacokinetics and modulate drug release. The prospect of surface modification, increased penetration across multiple biological barriers, chemical resistance, and the capacity to encapsulate two or more therapeutic substances simultaneously leads to widespread interest in solid lipid nanoparticles.

Targeted ACE inhibitors for the Treatment of Dilated Cardiomyopathy (DCM)

Dilated cardiomyopathy, a subtype of cardiomyopathies characterized by ventricular dilation, particularly of the left or both ventricles, coupled with systolic impairment, represents a heterogeneous condition distinct from valvular heart disorders, congenital cardiac anomalies, hypertensive cardiomyopathy, and acyanotic heart diseases. This article explores the varied categories of angiotensin-converting enzyme (ACE) inhibitors and their precise molecular targets. As a relatively uncommon disease entity, dilated cardiomyopathy lacks a definitive pharmacological cure and is managed primarily through medical therapy or surgical interventions. Emerging therapeutic modalities, such as left ventricular assist device (LVAD) support, have been introduced, yet the majority of these treatments necessitate careful consideration due to their specific indications and potential implications. Keywords: dilated cardiomyopathy, drug targeting, ACE inhibitors

Thermal study of Fe3O4/blood and CoFe2O4/blood magneto nanofluids study over an exponential surface inspired by convective heating and radiations

This work examines the role of Fe3O4/blood and CoFe2O4/blood nanofluids across an exponential surface associated to magnetic field, thermal radiation, and convective heating. It provides better thermal conductivity, biomedical application (such as drug targeting for treatment), and excellent efficiency of heat transfer, significant for the hyperthermia treatment and new hemodynamic systems. Thus, a bionanofluid model under mentioned physical constraints through an exponential surface is modeled. The formulation leads to a nonlinear mathematical model with enhanced characteristics of bionanofluid which then investigated numerically for physical responses of the parameters. It is examined that thermal efficiency of Fe3O4/blood is higher than CoFe2O4/blood due to strengthening the concentration and radiation effects. Intensive magnetic field and convective heating provided considerable thermal improvement in Fe3O4/blood and CoFe2O4/blood which point towards the use of Fe3O4 as a reliable option for magnetic hyperthermia and controlled thermal treatment in biomedical systems. Further, the shear drag in CoFe2O4/blood diminishes rapidly than Fe3O4/blood due to enhanced magnetic field and stretching of the surface. The outcomes demonstrate the applicability of Fe3O4 to areas where efficient heat transfer is demanded in biomedical or thermal applications.

The Magic of Drug Targeting Is "Secretly" Tied to Optimal Drug Distribution and Exposure.

The Magic of Drug Targeting Is "Secretly" Tied to Optimal Drug Distribution and Exposure.

Medication targeting to subcellular organelles: Emphasizing mitochondria as a therapeutic marvel-Current situation and future prospects.

Medication targeting to subcellular organelles: Emphasizing mitochondria as a therapeutic marvel-Current situation and future prospects.

Review: Solid Dispersion Formulation Methods and Applications in Drug Delivery

About 44% of the active medicinal components in all previously disclosed chemical units are hydrophobic and do not extend shop because of their limited water solubility. One of the factors limiting the rate at which oral medications can reach the appropriate concentration in the systemic circulation for pharmacological action is their solubility. Our medical preparation scientists and researchers are constantly surrounded by issues relating to drug release, drug targeting, solubility, overdosing, permeability and bioavailability. Thus, creating or improving frameworks for drug delivery is a territory of ongoing research. Solid dispersion, micronization, salt formation, are some of the vital methods usually employed to improve the solubility of poorly soluble drugs, but each method has some drawbacks and benefits. This review focuses on different methods of improving drug solubility in order to lower the proportion of medication candidates that are removed from development due to poor solubility. The popular solution for all problems related to aspects of solubility and in vitro release rate of certain poorly watersoluble drugs, is solid dispersion. Solid dispersions smear the standard to drug release via producing a combination of a poorly water-soluble active pharmaceutical ingredients (API) and greatly soluble coformers. The solid dispersion method has been commonly used to increase the in vitro drug release, solubility, and bioavailability of poorly watersoluble drugs. The focus of this review paper is on carriers, BCS classification, and solubility. This page also summarizes some of the most current technological advancements and offers a variety of preparation methods for solid dispersion. The various solid dispersions were highlighted according to their molecular configuration and carrier type. It also provides an overview of the solid dispersion methodologies and their mechanics, as well as the marketed medications that can be made utilizing them.

In-silico investigation integrated with machine learning to identify potential inhibitors targeting AKT2: Key driver of cancer cell progression and metastasis.

In-silico investigation integrated with machine learning to identify potential inhibitors targeting AKT2: Key driver of cancer cell progression and metastasis.

Integrative multi-omics analysis reveals BEST1 as a potential tumor-associated gene in gliomas.

Integrative multi-omics analysis reveals BEST1 as a potential tumor-associated gene in gliomas.

Characterization and treatment outcomes of biologic therapy in super-responders and biologic-refractory psoriasis patients: A single-center retrospective study in China.

Characterization and treatment outcomes of biologic therapy in super-responders and biologic-refractory psoriasis patients: A single-center retrospective study in China.

ROS-Responsive Nanosystem Targeted Co-Delivery YC-1 and Regorafenib to Alleviate Hypoxia Enhancing Hepatocellular Carcinoma Therapy

PurposeThe current treatment of hepatocellular carcinoma (HCC) is confronted with anoxic drug resistance and significant side effects. To address these issues, a Reactive Oxygen Species (ROS)-responsive and targeted nano drug delivery system named REG/YC-1@PTP-RGD NPs (RYP-RGD NPs) was designed for the co-delivery of Regorafenib (REG) and the hypoxia inhibitor 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1).MethodsRYP-RGD NPs were fabricated through the self-assembly method. A series of techniques, such as transmission electron microscopy (TEM), UV-visible spectroscopy, and others, were employed to characterize their properties. In Vitro investigations encompassed drug release assays, cytotoxicity evaluations using Cell Counting Kit-8 (CCK-8) and other methods, cell uptake experiments, and Western blot analysis. In vivo, the biodistribution of RYP-RGD NPs was tracked by IVIS imaging, and their antitumor efficacy and biosafety were assessed in a HepG2 tumor-bearing mouse model with histological staining and biochemical analysis.ResultsRYP-RGD NPs exhibited a spherical morphology with an appropriate size and excellent dispersion. They demonstrated ROS-triggered drug release behavior. In vitro studies revealed good tumor-targeting ability, enhanced cytotoxicity against HCC cells, and the downregulation of hypoxia-inducible factor-1α (HIF-1α) by YC-1. In vivo experiments showed improved tumor targeting, significant inhibition of tumor growth, and lower toxicity compared to single drugs.ConclusionThe successfully developed RYP-RGD NPs offer a novel strategy for HCC treatment. They enhance drug targeting, synergistically boost the therapeutic effect, and maintain biosafety, showing great potential for clinical translation.

Small-molecule-induced liquid-liquid phase separation suppresses the carcinogenesis of β-catenin

Biomolecular condensates are droplet-like membrane-less compartments in cells that can sequester proteins. Modulating these condensates offers a promising way to durably inhibit disease-driving proteins that lack enzymatic activity and thus elude traditional drug targeting. However, many such proteins remain beyond the reach of current condensate-modulating strategies. Here we show an alternative approach: by destabilizing target proteins, we directly induce their liquid–liquid phase separation (LLPS), causing them to form condensates. Using this strategy, we develop a small molecule RQ that forces β-catenin (an oncogenic protein in liver cancer) into cytoplasmic condensates. This sequestration prevents β-catenin from entering the nucleus and activating cancer-promoting genes. In nanoparticle form (albumin-bound Abroquinone), RQ is selectively taken up by β-catenin-driven liver cancer cells and kills them while sparing normal cells. This approach suppresses β-catenin-driven tumor growth and overcomes immune evasion, demonstrating a promising paradigm for targeting previously untargetable proteins by inducing their phase separation.

An Enzyme-responsive Porphyrin Metal-organic Framework Nanosystem for Targeted and Enhanced Synergistic Cancer Photo-chemo Therapy.

The clinical efficiency of photodynamic therapy (PDT) in combination with chemotherapy has proven to be a promising strategy for tumor treatment, yet is restricted by the high glutathione (GSH) concentration at the tumor site and nonspecific drug targeting. The goal of the current research was to create a biocompatible GSH-depleting and tumor- targeting nanoparticle (denoted as DOX/CA@PCN-224@HA) for the combined photodynamic and chemo photo-chemo) therapy. The nanoparticles were characterized by transmission electron microscopy (TEM). A UV-vis spectrophotometer was used to measure the drug loading efficiency (DE) and encapsulation efficiency (EE). The GSH-depleting ability was measured using Ellman's test. Confocal laser scan microscopy (CLSM) was used to assess the cellular uptake. MTT was adopted to evaluate the cytotoxicity of DOX/CA@PCN-224@HA against 4T1 cells. The altered PCN-224 showed excellent monodispersing with a dimension of approximately 193 nm ± 2 nm in length and 79 nm ± 3 nm in width. The larger and spindle grid-like structure of PCN-224 obtains better dual-drug loading ability (DOX: 20.58% ± 2.60%, CA: 21.81% ± 1.98%) compared with other spherical PCN-224 nanoparticles. The ultimate cumulative drug release rates with hyaluronidase (HAase) were 74% ± 1% (DOX) and 45% ± 2% (CA) after 72 h. DOX/CA@PCN-224@HA showed GSH-consuming capability, which could improve the PDT effect. The drug-loaded nanoparticles could accurately target 4T1 cells through biological evaluations. Moreover, the released DOX and CA display cooperative effects on 4T1 cells in vitro. DOX/CA@PCN-224@HA nanoparticles showed inhibition against 4T1 cells with an IC50 value of 2.71 μg mL-1. This nanosystem displays great potential for tumor-targeted enhanced (photo-chemo) therapy.

Electrochemical interpretations for the study of molnupiravir binding interactions with bovine serum albumin and DNA and molecular dynamics studies.

Electrochemical interpretations for the study of molnupiravir binding interactions with bovine serum albumin and DNA and molecular dynamics studies.

Platelet Membrane-Coated Poly (Lactic-Co-Glycolic Acid) Nanoparticles as a Targeting Drug Delivery System for Multidrug-Resistant Breast Cancer.

Paclitaxel (PTX), widely used chemotherapeutic agent, is limited by poor solubility, P-glycoprotein (P-gp) mediated efflux, and non-specific toxicity. To overcome these challenges, we developed a triple-functionalized nanocarrier system incorporating poly(lactide-co-glycolide) (PLGA)-based nanoparticles (PNs), D-α-tocopheryl polyethylene glycol succinate (TPGS) for P-gp inhibition, and platelet membrane (PM) coating for targeted tumor delivery. The PM-coated TPGS-modified PNs with PTX (PTPNs) was characterized by particle size analysis, transmission electron microscopy (TEM), and protein assay to confirm PM coating. In vitro drug release studies were conducted under acidic conditions mimicking the tumor microenvironment. Cellular assays were performed to evaluate cytotoxicity and drug efficacy in multidrug-resistant MCF-7/ADR cells. In vivo biodistribution and xenograft studies assessed tumor accumulation and therapeutic outcomes. PTPNs exhibited a particle size of 221 ± 2 nm with a PDI of 0.090 ± 0.020 and a zeta potential of -30.5 ± 0.3 mV, indicating a homogeneous particle distribution and successful PM coating. The optimal PM-to-PLGA weight ratio was determined to be 0.005, which ensured structural stability and uniform coating in physiological conditions. Sustained PTX release was observed in acidic conditions, mimicking the tumor microenvironment. Cellular assays showed a 17-fold reduction in PTX IC50 in MCF-7/ADR cells compared to free PTX, attributed to the synergistic effects of TPGS-mediated P-gp inhibition and PM-based tumor targeting. In vivo, PTPNs demonstrated enhanced tumor accumulation and significantly reduced tumor burden, with final tumor volume 2.6-fold lower than that of TPNs and 3.6-fold lower than that of the PTX commercial product (Taxol®)-treated group. Tumor necrosis factor-α (TNF-α) levels were also reduced, reflecting decreased tumor-promoting cytokine activity. The PTPNs enhanced PTX delivery by improving tumor specificity, overcoming multidrug resistance, and reducing systemic toxicity. These results suggested the potential of this biomimetic approach to advance cancer therapy.