ACS Applied Bio Materials

Research on the Effect of NK Cells Based on Functionalized Magnetic Beads on Cervical Cancer Mice

In recent years, the incidence of tumors has shown an increasing trend, while traditional treatment methods such as surgery, radiotherapy, and chemotherapy exhibit certain limitations. Immunotherapy has been extensively investigated in the field of cancer treatment due to its advantages of high specificity in recognition, significant inhibition of tumor growth and proliferation, and the absence of adverse effects on the structure and function of normal tissue cells. Natural killer (NK) cells, as crucial components of the innate immune system, play a pivotal role in antitumor immune responses. In this study, a magnetic nanocarrier loaded with NK cells was constructed to combine magnetic targeting with NK immunotherapy. By integrating magnetic targeting with NK cell immunotherapy, this system enhances NK cell infiltration at tumor sites through external magnetic field guidance, thereby improving the tumor-killing efficacy. The main research contents are as follows: nanoscale Fe

Macrophage Checkpoint Nanoimmunotherapy Has the Potential to Reduce Malignant Progression in Bioengineered In Vitro Models of Ovarian Cancer

Most ovarian carcinoma (OvCa) patients present with advanced disease at the time of diagnosis. Malignant, metastatic OvCa is invasive and has poor prognosis, exposing the need for improved therapeutic targeting. High CD47 (OvCa) and SIRPα (macrophage) expression has been linked to decreased survival, making this interaction a significant target for therapeutic discovery. Even so, previous attempts have fallen short, limited by CD47 antibody specificity and efficacy. Macrophages are an important component of the OvCa tumor microenvironment and are manipulated to aid in cancer progression via CD47-SIRPα signaling. Thus, we have leveraged lipid-based nanoparticles (LNPs) to design a therapy uniquely situated to home to phagocytic macrophages expressing the SIRPα protein in metastatic OvCa. CD47-SIRPα presence was evaluated in patient histological sections using immunohistochemistry. 3D tumor spheroids generated on a hanging drop array with OVCAR3 high-grade serous OvCa and THP-1-derived macrophages created a representative model of cellular interactions involved in metastatic OvCa. Microfluidic techniques were employed to generate LNPs encapsulating SIRPα siRNA (siSIRPα) to affect the CD47-SIRPα signaling between the OvCa and macrophages. siSIRPα LNPs were characterized for optimal size, charge, and encapsulation efficiency. Uptake of the siSIRPα LNPs by macrophages was assessed by Incucyte. Following 48 h of 25 nM siSIRPα treatment, OvCa/macrophage heterospheroids were evaluated for SIRPα knockdown, platinum chemoresistance, and invasiveness. OvCa patient tumors and

Molecular Insights into Paclitaxel and Curcumin-Loaded Carbon Dots: Computational and Experimental Evidence of NRF2 and Autophagy Modulation in Ovarian Cancer

Ovarian cancer remains a highly aggressive and deadly gynecological malignancy, primarily due to acquired chemoresistance. Curcumin, a natural compound with potent anticancer properties, is limited by poor bioavailability, hindering its clinical application. This study investigates nitrogen and boron codoped carbon dots (NBCDs) as a nanocarrier to enhance curcumin delivery and therapeutic efficacy against chemoresistant ovarian cancer. NBCDs were synthesized via a one-pot hydrothermal method and characterized for their physicochemical properties. We evaluated the cellular uptake and cytotoxic effects of curcumin-loaded NBCDs (CUR-NBCDs) and paclitaxel-loaded NBCDs (PTX-NBCDs) in OVCAR3 and SKOV3 ovarian cancer cell lines. Oxidative stress markers, autophagy induction, and NRF2 pathway modulation were analyzed using fluorescence microscopy, biochemical assays, and qPCR. Molecular docking and dynamics simulations were employed to study drug interactions with key autophagy regulatory proteins. Results demonstrated that NBCDs exhibit excellent biocompatibility and enhance curcumin's cellular uptake. CUR-NBCDs effectively induced autophagy, evidenced by acridine orange staining and modulation of autophagy markers. Molecular analysis revealed downregulation of NRF2 and P62, and upregulation of BECLIN1, indicating NRF2 pathway suppression and enhanced autophagic flux. Molecular docking and dynamics simulations confirmed stable interactions between curcumin and autophagy regulatory proteins. In conclusion, NBCDs enhance curcumin's bioavailability and therapeutic efficacy by modulating the NRF2-autophagy axis, offering a potential therapeutic approach to address ovarian cancer chemoresistance through dual targeting of oxidative stress and autophagy pathways.

Photothermal-Induced Electrochemical Interfacial Region Regulation Enables Signal Amplification for Dual-Mode Detection of Ovarian Cancer Biomarkers

Detection sensitivity of an electrochemical immunosensor mainly depends on the accessible distance toward the sensing interface; regulating the electrochemical interfacial region thereon is an effective strategy for signal amplification. Herein, a photothermal-regulated sensing interface was designed based on a near-infrared (NIR)-responsive hydrogel probe for ultrasensitive detection of human epididymis protein 4 (HE4). Silver nanoparticle-deposited graphene oxide nanosheet (AgNPs@GO) hybrids as electrochemical signal tags and a photothermal transducer, which were encapsulated in the poly(

Molybdenum Disulfide Supported on Metal–Organic Frameworks as an Ultrasensitive Layer for the Electrochemical Detection of the Ovarian Cancer Biomarker CA125

Metal-organic frameworks (MOFs) are composed of metal ions/clusters and organic ligands, showing accessible functional sites, ultra-high porosity, and large specific surface area. Tricopper benzene-1,3,5-tricarboxylate (CuBTC), as a three-dimensional MOF architecture with an open and robust micro-/nanoconfiguration, possesses excellent catalytic performance and superior electric conductivity as compared to bulk MOF. In this study, CuBTC was used as a substrate on which molybdenum disulfide (MoS

Noninvasive Point-of-Care Nanobiosensing of Cervical Cancer as an Auxiliary to Pap-Smear Test

A potential cancer antigen (Ag), protein-phosphatase-1-gamma-2 (PP1γ2), with a restricted expression in testis and sperms has been identified as a biomarker specific to cervical cancer (CaCx). Detection of this cancer biomarker antigen (NCB-Ag) in human urine opens up the possibility of noninvasive detection of CaCx to supplement the dreaded and invasive Pap-smear test. A colorimetric response of an assembly of gold nanoparticles (Au NPs) has been employed for the quantitative, noninvasive, and point-of-care-testing of CaCx in the urine. In order to fabricate the immunosensor, Au NPs of sizes ∼5-20 nm have been chemically modified with a linker, 3,3'-di-thio-di-propionic-acid-di(

Design of Bio-Graphene-Based Multifunctional Nanocomposites Exhibits Intracellular Drug Delivery in Cervical Cancer Treatment

The advent of bio-nanotechnology has revolutionized nanodrug delivery by improving drug efficacy and safety. Nevertheless, acceptable carriers for therapeutic molecules are one of the most difficult challenges in drug delivery. Graphene material-based (GMB) and polymer-based drug-loaded nanocarriers have both demonstrated clinical advantages in delivering drugs of interest

Recent Advances in Diagnostic Strategies and Nanotechnology-Based Therapies for Ovarian Cancer Treatment

Ovarian cancer is a global silent killer in women and is the second most common cause of gynecologic cancer-related deaths. Despite significant research and advances in treatment, ovarian cancer treatment remains a challenge, as it is diagnosed in an advanced stage and has a very high rate of recurrence following initial therapy. There is a compelling need to develop effective therapeutics for the treatment of ovarian cancer. This review highlights the recent advancements in nanoparticle-based drug-delivery systems and their expanding scope of treatments and diagnostics in ovarian cancer. In this article, we provide an overview of the innate immune response elicited by external delivery carriers. The review details the ongoing progress in nanotechnology for ovarian cancer treatment, including advances in nanoimmunotherapy and the potential of nanoparticle-based formulations for combating ovarian cancer. Recent diagnostic and prognostic tools used for ovarian cancer have been elaborated. The review also underscores the role of artificial intelligence in advancing current clinical diagnosis protocols. Challenges and future perspectives of nanocarriers for ovarian cancer treatment are also discussed in detail. This review uniquely integrates the role of innate immune responses with advances in nanotechnology for ovarian cancer, providing a comprehensive and interdisciplinary perspective that has not been previously addressed.

Multifunctional Tandem Peptide Mediates Targeted siRNA Delivery to Ovarian Cancer Cells

Fusogenic peptides have been developed to enhance the delivery efficiency of nucleic acids such as small interfering RNAs (siRNAs). Fusogenic peptides can protect nucleic acids from degradation and facilitate endosomal escape, but their systemic delivery capabilities remain unrefined. Active targeting of delivery systems to overexpressed cell receptors can be used to enhance cell- and tissue-specific delivery of therapeutic payloads while reducing off-target and systemic effects. We aimed to develop a targeted fusogenic (tandem) peptide, LHRHR-DIV3W, capable of targeting the luteinizing hormone-releasing hormone receptor (LHRHR), which is overexpressed in ovarian cancer cells and tissues. Characterization studies revealed that our tandem peptide, LHRHR-DIV3W, formed monodisperse nanocomplexes that protected siRNAs in physiological environments. We also demonstrated receptor-specific internalization of peptide-siRNA nanocomplexes in ovarian cancer cell lines with upregulated LHRHR expression. Furthermore, we observed that the inclusion of both the fusogenic DIV3W sequence and the LHRHR-targeting sequences in the tandem peptide enhanced receptor-specific siRNA internalization in ovarian cancer cells by up to 40% compared with the LHRHR-targeting peptide alone, indicating the necessity of combining both peptide regions. Finally, we demonstrated significant silencing of

Recent Advances in Nanotechnology-Based Drug Delivery Systems for the Diagnosis and Treatment of Reproductive Disorders

NIR Triggered Fluorescence Imaging and Synergistic Ablation of Cervical Cancer Using ICG-Loaded CuO Nanoleaves via Photothermal-Augmented ROS Amplification

Developing Cu-based nanocatalysts capable of generating sufficient reactive oxygen species (ROS) to effectively inhibit tumor cell growth remains a significant challenge. In this study, we introduce a distinctive copper oxide nanocarrier with a unique leaf-like lamina structure and layered mesopores. Indocyanine Green (ICG) is encapsulated within the mesopores, and poly(ethylene glycol) (PEG) groups are attached to the surface. This nanoplatform demonstrates efficient accumulation in tumor areas, serving as a near-infrared (NIR) fluorescent contrast agent for tumor imaging. Remarkably, under NIR laser irradiation, the nanoplatform exhibits high photothermal conversion efficiency, which enhances ROS production through localized heating. Both

Gold-Coated Glybosomes Mimicking Physiological Micelles for ROS-Mediated Photothermal Ablation against Cervical Cancer

Highly hydrophobic secondary bile acid, Lithocholic acid, is known for its significant roles in bile metabolism, lipid absorption, and enterohepatic circulation. Recently, emerging research has indicated its biological significance in modulating cell signaling pathways via receptors such as Farnexoid X- Receptor (FXR), G-Protein Coupled Bile acid Receptor (GPBAR) otherwise called as Takeda G protein-coupled receptor-5 (TGR5) and Vitamin-D Receptor (VDR). It has also been reported to exhibit various biological functions such as anti-inflammatory, antimicrobial, and anticancer activities. In this study, we have developed Glybosomes (GLBs), a lithocholic acid containing liposomes through a facile method, and have subsequently coated them with gold (Au@GLB) for using them as an effective photothermal agent. The developed Glybosomes showed enhanced cytotoxicity, good biocompatibility, hemocompatibility, and promoted apoptosis against cervical cancer. Mechanistic studies also revealed that the promoted cell death was due to reactive oxygen species (ROS) generation, disruption of the mitochondrial membrane potential, and DNA damage. These findings demonstrate that Au@GLB NPs is a promising nanoformulation for effective photothermal therapy against cervical cancer treatment.

Nanoarchitectures of Folate-Functionalized Highly Monodispersed Ce–Tb Doped Core@Shell Nanorods for Targeted and Enhanced Chemotherapy of Human Cervical and Triple-Negative Breast Carcinoma

The high incidence, aggressiveness, and chemo-refractory nature of cervical and triple-negative breast cancers (TNBC) warrant the development of targeted chemotherapy strategies for improving their therapeutic outcomes. The present study reports the design and preparation of highly monodispersed, biocompatible, and hemocompatible Ce-Tb-doped core@shell NaGdF