ACS Applied Materials & Interfaces

Engineering Magnetic Extracellular Vesicles Mimetics for Enhanced Targeting Chemodynamic Therapy to Overcome Ovary Cancer

Chemodynamic therapy (CDT), employing metal ions to transform endogenous H

A Macrophage-Driven Multimodal Nanoplatform Conquers Ovarian Cancer Peritoneal Metastasis

Ovarian cancer peritoneal metastasis remains a lethal clinical challenge, with hyperthermic intraperitoneal chemotherapy (HIPEC) offering limited survival benefits due to off-target toxicity, position-dependent delivery, and the lack of durable immune activation. Herein, we report a macrophage-driven precision nanoplatform that enables tumor-homing delivery and multimodal therapeutic synergy. By engineering M1-polarized, tumor-tropic macrophages to deliver mitoxantrone (MTO)-loaded metal-organic framework nanoparticles (MTO NPs@M1), we achieve selective accumulation at peritoneal metastases via the innate homing capacity of macrophages. Upon near-infrared (NIR) irradiation, the system triggers on-demand release of MTO NPs, enabling a trimodal therapeutic strategy: (I) chemotherapy via MTO-induced DNA damage, (II) photothermal ablation, and (III) chemodynamic therapy (CDT) through Cu-MOF-mediated •OH generation. This combined strategy induces strong immunogenic cell death (ICD), promoting dendritic cell maturation and cytotoxic T cell infiltration. Combined with anti-PD-L1 checkpoint blockade, the platform achieves near-complete eradication of peritoneal metastases in murine ovarian cancer and elicits robust adaptive immune memory that prevents recurrence, as confirmed in a tumor rechallenge model. By integrating targeted delivery, multimodal tumor eradication, and immune activation, this strategy addresses the limitations of conventional HIPEC and provides a promising translational approach for ovarian cancer peritoneal metastasis.

Functionalized Mildly Oxidized MXene-Based Injectable Hydrogel with Enhanced Photothermal Performance for Precision Therapy of Uterine Sarcoma

Uterine sarcoma is an extremely malignant gynecological tumor, characterized by rapid growth, early metastasis, and a high recurrence rate. Current treatments like surgery, radiotherapy, and chemotherapy, have limited effectiveness, highlighting the urgent need for innovative noninvasive alternatives. Here, we report a novel photosensitive nanocomposite hydrogel (O1-M&F) designed for NIR-induced photothermal therapy (PTT), comprising mildly oxidized MXene (O1-M) and a thermosensitive Pluronic F127 hydrogel. Unlike conventional approaches that aim to prevent MXene oxidation, we demonstrate that mild oxidation significantly enhances both the photothermal conversion efficiency and reactive oxygen species (ROS) generation of MXene nanosheets. The incorporation of F127 hydrogel further ensures the long-term dispersion stability and biocompatibility of the composite system. In vitro and in vivo studies demonstrated potent tumor ablation capability with minimal side effects. Increased apoptosis of uterine sarcoma cells was further observed. The biocompatibility of the O1-M&F hydrogel was validated, indicating its potential for safe and effective therapeutic application. These findings suggest that O1-M&F-based PTT is a promising, noninvasive, effective treatment for uterine sarcoma, offering a novel therapeutic approach with reduced risks and enhanced patient outcomes.

Bola-Amphiphilic Dendrimer Enhances Imatinib to Target Metastatic Ovarian Cancer via β-Catenin-HRP2 Signaling Axis

Ovarian cancer is the leading cause of death among all gynecological malignancies, and drug resistance renders the current chemotherapy agents ineffective for patients with advanced metastatic tumors. We report an effective treatment strategy for targeting metastatic ovarian cancer involving a nanoformulation (Bola/IM)─bola-amphiphilic dendrimer (Bola)-encapsulated imatinib (IM)─to target the critical mediator of ovarian cancer stem cells (CSCs) CD117 (c-Kit). Bola/IM offered significantly more effective targeting of CSCs compared to IM alone, through a novel and tumor-specific β-catenin/HRP2 axis, allowing potent inhibition of cancer cell survival, stemness, and metastasis in metastatic and drug-resistant ovarian cancer cells. Promising results were also obtained in clinically relevant patient-derived ascites and organoids alongside high tumor-oriented accumulation and favorable pharmacokinetic properties in mouse models. Furthermore, Bola/IM displayed synergistic anticancer activity when combined with the first-line chemotherapeutic drug cisplatin in patient-derived xenograft mouse models without any adverse effects. Our findings support the use of Bola/IM as a nanoformulation to empower IM, providing targeted and potent treatment of metastatic ovarian cancer. Our study thus represents a significant advancement toward addressing the unmet medical need for improved therapies targeting this challenging disease.

Selective Anticervical Cancer Injectable and Self-Healable Hydrogel Platforms Constructed of Drug-Loaded Cross-Linkable Unimolecular Micelles in a Single and Combination Therapy

In the face of severe side effects of systemic chemotherapy used in cervical cancer, topical selective drug carriers with long-lasting effects are being sought. Hydrogels are suitable platforms, but their use is problematic in the case of delivery of hydrophobic drugs with anticancer activity. Herein, hydrogels constructed of unimolecular micelles displaying enhanced solubilization of aromatic lipophilic bioactive compounds are presented. Star-shaped poly(benzyl glycidyl ether)-

In Vivo SELEX: A Strategy for Identifying Ovarian Cancer-Specific Aptamers

Ovarian cancer is a significant and life-threatening malignancy among women worldwide. Selective tumor targeting by molecular agents is essential for the development of effective therapeutics and diagnostics. Recognizing the disparities between in vivo and in vitro environments, we have implemented an in vivo SELEX strategy to identify DNA aptamers capable of specifically localizing to ovarian tumors in situ. Aptamer L1 has emerged as a promising candidate with a high binding affinity to Insulin-like Growth Factor Binding Protein 3 (IGFBP3), a tumor-promoting protein overexpressed in ovarian cancer. Notably, aptamer L1 effectively downregulates IGFBP3 expression and suppresses ovarian cancer cell proliferation. The unique molecular characteristics of aptamer L1 underscore its potential as a theranostic agent for ovarian cancer.

Spatiotemporal Circadian Oscillator Manipulation for Enhanced Ovarian Cancer Therapy Using a Versatile Nanoplatform

Circadian rhythm (CR) disruption has been confirmed as a contributing factor to tumor progression. However, regulating circadian genes shows an inhibitory effect on ovarian tumor initiation and progression, which highlights the urgent necessity to regulate tumors' CR to understand their role in ovarian cancer (OC) therapy precisely. Herein, a novel near-infrared (NIR) light-controlled spatiotemporal strategy is presented, aiming to manipulate ovarian tumors' CR while enhancing the efficacy of chemotherapy agents. To achieve this strategy, a versatile nanoplatform (NP

Near-Infrared Emissive Lanthanide Metal–Organic Frameworks for Targeted Biological Imaging and pH-Controlled Chemotherapy

Near-infrared window II (NIR-II, 1000-1700 nm) imaging displays the advantages in deep-tissue high-contrast imaging in vivo on the strength of the high temporal-spatial resolution and deeper penetration. However, the clinical utility of NIR-II imaging agents is limited by their single function. Herein, for the first time, we report the design of a multifunctional drug delivery system (DDS) assembly, CQ/Nd-MOF@HA nanohybrids, with NIR-II fluorescence (1067 nm), large Stokes shifts, and ultrahigh quantum yield, which combined targeted NIR-II luminescence bioimaging and pH-controlled drug delivery. The nanoscale metal-organic framework (MOF) as a highly promising multifunctional DDS for targeted NIR-II bioimaging and chemotherapy in vitro and in vivo lays the foundation of the MOF-based DDS for further clinical diagnosis and treatment.

Yolk–Shell-Type Gold Nanoaggregates for Chemo- and Photothermal Combination Therapy for Drug-Resistant Cancers

Epithelial ovarian cancer is a gynecological cancer with the highest mortality rate, and it exhibits resistance to conventional drugs. Gold nanospheres have gained increasing attention over the years as photothermal therapeutic nanoparticles, owing to their excellent biocompatibility, chemical stability, and ease of synthesis; however, their practical application has been hampered by their low colloidal stability and photothermal effects. In the present study, we developed a yolk-shell-structured silica nanocapsule encapsulating aggregated gold nanospheres (aAuYSs) and examined the photothermal effects of aAuYSs on cell death in drug-resistant ovarian cancers both

Silicane Derivative Increases Doxorubicin Efficacy in an Ovarian Carcinoma Mouse Model: Fighting Drug Resistance

The development of cancer resistance continues to represent a bottleneck of cancer therapy. It is one of the leading factors preventing drugs to exhibit their full therapeutic potential. Consequently, it reduces the efficacy of anticancer therapy and causes the survival rate of therapy-resistant patients to be far from satisfactory. Here, an emerging strategy for overcoming drug resistance is proposed employing a novel two-dimensional (2D) nanomaterial polysiloxane (PSX). We have reported on the synthesis of PSX nanosheets (PSX NSs) and proved that they have favorable properties for biomedical applications. PSX NSs evinced unprecedented cytocompatibility up to the concentration of 300 μg/mL, while inducing very low level of red blood cell hemolysis and were found to be highly effective for anticancer drug binding. PSX NSs enhanced the efficacy of the anticancer drug doxorubicin (DOX) by around 27.8-43.4% on average and, interestingly, were found to be especially effective in the therapy of drug-resistant tumors, improving the effectiveness of up to 52%. Fluorescence microscopy revealed improved retention of DOX within the drug-resistant cells when bound on PSX NSs. DOX bound on the surface of PSX NSs, i.e., PSX@DOX, improved, in general, the DOX cytotoxicity in vitro. More importantly, PSX@DOX reduced the growth of DOX-resistant tumors in vivo with 3.5 times better average efficiency than the free drug. Altogether, this paper represents an introduction of a new 2D nanomaterial derived from silicane and pioneers its biomedical application. As advances in the field of material synthesis are rapidly progressing, novel 2D nanomaterials with improved properties are being synthesized and await thorough exploration. Our findings further provide a better understanding of the mechanisms involved in the cancer resistance and can promote the development of a precise cancer therapy.

Novel Platinum Nanoclusters Activate PI3K/AKT/mTOR Signaling Pathway-Mediated Autophagy for Cisplatin-Resistant Ovarian Cancer Therapy

Platinum (Pt)-based chemotherapy drugs such as cisplatin are the first line and core options for the treatment of ovarian cancer (OC), while cisplatin resistance has a worse prognosis and low 5 year survival rate for patients. Chemotherapeutic drugs synthesized from nanomaterials have shown great potential in biomedicine; however, research into their application for OC resistance is rarely discussed. This study is proposed to elucidate the anti-tumor effects of polyethylenimine (PEI)-caged platinum nanoclusters (Pt NCs) on cisplatin-resistant OC. The results of confocal microscopy showed that Pt NCs entered cisplatin-resistant OC cells dose-dependently and aggregated both in the cytoplasm and inside the nucleus. Subsequently, according to the results of CCK8 assay, wound healing assay, clone formation assay, Transwell assay, Ki-67 immunofluorescence assay, and flow cytometry assay, the proliferation and migration of cisplatin-resistant OC cells were inhibited by Pt NCs, as well as their apoptosis was promoted. In addition, we validated the anti-tumor effect of Pt NCs on regulating autophagy via monodansylcadaverine (MDC) staining, transmission electron microscopy observation of the autophagic ultrastructure, LC3-II-GFP and P62-GFP adenovirus single-label immunofluorescence, and western blotting; meanwhile, the role of Pt NCs in adjusting autophagy through modulation of the PI3K-AKT-mTOR signaling was verified. Based on these results, it appears that cisplatin-resistant OC cells can undergo apoptosis when Pt NCs activate autophagy by inhibiting the PI3K/AKT/mTOR pathway, exhibiting a promising potential of Pt NCs in the development of a novel chemotherapeutic agent for patients suffering from cisplatin-resistant OC.

Engineering Chemotherapeutic-Augmented Calcium Phosphate Nanoparticles for Treatment of Intraperitoneal Disseminated Ovarian Cancer

Ovarian cancer is a common gynecologic malignancy with a high fatality rate. Intraperitoneal chemotherapy has been proved as an efficient clinical treatment for disseminated ovarian cancer. However, there are limitations for conventional small molecule drugs to achieve an ideal therapeutic effect. Herein, a synergistic treatment for intraperitoneally disseminated ovarian cancer was achieved by Arg-Gly-Asp (RGD)-modified amorphous calcium phosphate loading with doxorubicin (designated as RGD-CaPO/DOX). The engineered calcium-involved nanomedicine augmented the therapeutic effect of DOX by aggravating endoplasmic reticulum stress, calcium overload, and mitochondrial dysfunction, ultimately triggering mitochondrial apoptosis in the SKOV3 (human ovarian cancer) cell line. In an intraperitoneally disseminated tumor model, RGD modification and the weak negative surface potential of the NPs were beneficial for intraperitoneal retention and tumor targeting. Moreover, intraperitoneal injection of RGD-CaPO/DOX NPs resulted in a favorable antitumor effect. The mean survival time of SKOV3-bearing mice was significantly extended from 29 to 59 days with negligible toxicity. Therefore, this study has been designed to provide an effective chemotherapeutic-augmented treatment for intraperitoneally disseminated ovarian cancer.

Multifunctional Human Serum Albumin Fusion Protein as a Docetaxel Nanocarrier for Chemo-photothermal Synergetic Therapy of Ovarian Cancer

Modification of inorganic nanoparticles with human serum albumin (HSA) that load with chemotherapeutic agents has been reported to conduct chemo-photothermal synergistic therapy of tumors. However, loading some highly insoluble drugs would cause the conformation disorder of HSA, which is unable to give full play to tumor targeting and biological compatibility. Besides, inorganic nanoparticles with too large of a size would appear with unsatisfactory metabolism and lead to biological toxicity. Herein, the recombinant protein integrating histidine (His), HSA, enzyme responsive site, and arginine-glycine-aspartic acid (RGD) by genetic engineering technology was developed to co-load docetaxel (DTX) and gold nanoparticles (Au NPs) to construct RHMH18@AuD NPs. In which, DTX was encapsulated in the micelle part that self-assembled by histidine, while ultrasmall Au NPs were clustered in the HSA part through biomimetic mineralization. RHMH18@AuD NPs could maintain a consistent conformation with HSA and a uniform dispersion in saline.

Chiral Carbon Dots-Enzyme Nanoreactors with Enhanced Catalytic Activity for Cancer Therapy

As a class of functional proteins, enzymes possess inherent insignificant features, for instance, mediocre stability and membrane impermeability and reduced enzymatic activity after modification, which partly limit their biomedical applications. Thus, it is indispensable to exploit robust nanoreactors with high enzymatic activity and good stability and cell permeability. Here, the chiral carbon dots (CDs)-glucose oxidase (GOx) nanoreactors named LGOx and DGOx were constructed by the coassembly of GOx with L/D-CDs, respectively. L/DGOx can significantly enhance the activity of GOx and improve the efficient delivery of GOx to cancer cells. Moreover, these nanoreactors can generate hydrogen peroxide to efficaciously kill cancer cells and restrain tumor growth, and DGOx exhibits higher enzymatic activity than LGOx. According to our understanding, this is the first report about utilizing chiral CDs as vectors to construct effective CDs-enzyme nanohybrids for cancer therapy, which is envisioned to be a versatile strategy for multitudinous biomedical applications.

Oxygen-Generating Hydrogels Overcome Tumor Hypoxia to Enhance Photodynamic/Gas Synergistic Therapy

Hypoxic environment is a bottleneck of photodynamic therapy (PDT) in tumor treatment, as oxygen is the critical substrate for photosensitivity reaction. Herein, a sustained oxygen supply system based on cerium nanoparticles and hydrogel (GHCAC) was explored for enhanced synergistic PDT and gas therapy. Ceria nanoparticles were prepared as a drug carrier by self-assembly mediated by hyaluronic acid (HA), a targeting for CD44 on cervical cancer cells, followed by photosensitizer and l-arginine (l-Arg) loading. Then, the GHCAC system was developed by incorporating a prepared nanocarrier (HCePA) and O

A Membrane-Retained DNA Aptamer Promotes Intracellular Platinum Accumulation and Chemosensitization in Ovarian Cancer

Cisplatin resistance remains a major obstacle in the effective treatment of ovarian cancer. Here, we report a membrane-retained DNA aptamer, DR-A2, discovered via Cell-SELEX using cisplatin-resistant ovarian cancer cells as the selection target. DR-A2 exhibited high affinity and specificity toward drug-resistant ovarian cancer cells and their secreted exosomes, while showing negligible binding to drug-sensitive parental cells or normal epithelial cells. Mechanistic studies revealed that DR-A2 increases intracellular cisplatin retention in resistant cells. In vivo, DR-A2 preferentially accumulated in cisplatin-resistant xenografts and significantly boosted the antitumor efficacy of cisplatin without causing systemic toxicity. These results validate DR-A2 as a bifunctional aptamer capable of both selective tumor recognition and chemosensitization, offering a promising strategy to overcome platinum resistance in ovarian cancer.

Collective Mechanical Memory Encoded by Long-Lasting Supracellular Cytoskeletal Structures in Multicellular Spheroids

Animal cells can sense and "remember" the stiffness of their extracellular environment, resulting in sustained changes in form and function. Such "mechanical memory" has been previously explored using individual cells and attributed to epigenetic changes and transcriptional activity. However, it is unclear whether such memory is retained across collective cells. Here, we report that collective cells sustain mechanical memory through self-organized actin-CK18 networks spanning multiple cell lengths, even under dramatically changing mechanical environments, such as those encountered during cancer metastasis. As a case study, we modeled ovarian cancer metastasis and found that cells initially cultured on different stiffness retained distinct migratory phenotypes throughout the environmental transitions of the metastasis model. Notably, soft-primed cells, in particular, demonstrated stronger cell-cell adhesions than stiff-primed cells. Upon aggregation into multicellular spheroids, mimicking malignant spheroids found in patient ascites, the soft-primed spheroids exclusively developed a dense cage-like supracellular actin-CK18 structure at their peripheral surfaces. Furthermore, these soft-primed spheroids exhibited impeded collective invasion, instead becoming confined by the long-lasting cytoskeletal cage. Inhibition of gap junctions attenuated the formation of cytoskeletal cages, indicating that dynamic intercellular communication via gap junctions is essential for maintaining collective mechanical memory. This work demonstrates a collective mechanism of mechanical memory that is not solely dependent on epigenetic and transcriptional activation, advancing our understanding of the elevated metastatic potential of tumor cell clusters originating in stiffened matrices.

Gel-to-Coacervate Transition in Peptide/HA Complexes for MMP-9-Activated Penetration into Tumor Spheroids

Short phase-separating peptides serve as liquid-based vehicles due to their remarkable fluidity and cell permeability, holding great promise in diffusion-limited applications such as intracellular drug delivery or penetration into deep-seated tumors. However, tuning the phase stability and the phase-transition sensitivity of these coacervates in response to specific pathological signals remains a significant challenge. To tackle this challenge, this study presents a phase-separating peptide/hyaluronic acid (HA) complex coacervate system, which undergoes a solid-to-coacervate transition upon exposure to matrix metalloproteinase 9 (MMP-9). By harnessing this disease-relevant enzyme, overexpressed in the ovarian tumor microenvironment, we further demonstrate the improved infiltration of the coacervates into Hey cells and tumor spheroids. These observations highlight the feasibility of modulating phase behaviors and advanced functions of coacervates through sequence-specific monomer design, offering a practical strategy for the on-target delivery of coacervates and medicine into tumors.

An Innovative 3D-IDE Design and Adaptive Signal Extraction Algorithm for Efficient Ovarian Cancer Detection

This work presents a facile, ultrasensitive, and selective chemiresistive biosensor assisted by an adaptive signal extraction algorithm (ASEA) for detecting vimentin, a potential biomarker for ovarian cancer detection. The low-cost device, fabricated on a PCB substrate through sacrificial copper etching, features a 3D-IDE design with interwoven comb-like structures mimicking the natural symmetry of a droplet. An unequal count of positive and negative concentric circle fingers ensures a uniform, higher electric field over the sensor's surface, as verified by COMSOL Multiphysics 3D simulation. This optimal electric field elegantly reflects changes in the IV characteristics, even with minor variations in surface charge density from probe-target interactions. Graphene oxide, functionalized with a heterobifunctional linker, serves as the sensing nanomaterial. A detailed study examines the device's response with interdigitated gaps from 30 to 150 μm. A wider interdigitated gap introduces greater variability in the response across different voltage levels. To address this, the Python-based ASEA meticulously scans the entire voltage range, isolating the segment of the signal that best balances both the intensity and extension for optimal expression. ASEA boosts the limit of detection (LOD) by five times for sensors with gaps of over 100 μm. The biosensor achieves a minimum LOD of 9.45 fg mL

Teaching an Old Dog New Tricks: A Global Approach to Enhancing the Cytotoxicity of Drug-Loaded, Non-responsive Micelles Using Oligoelectrolytes

Galectin-1-Targeted Type-I/II Photosensitizers Activate the NF-κB Pathway to Enhance Immunity and Treat High-Risk HPV-Associated Cervical Lesions

Persistent infection with high-risk HPV in women can progress to cervical intraepithelial neoplasia and even cervical cancer. This study investigated the cytotoxic and immunomodulatory effects of the TBTCN-TDG photodynamic therapy (PDT) probe in treating HPV-associated cervical lesions. The TBTCN-TDG probe was designed by integrating a donor-acceptor-π-acceptor 1 (D-A-π-A1) structure (TBTCN) with TDG, a moiety targeting Galectin-1, and its targeting ability in HPV-positive SiHa cells was confirmed. The in vitro results demonstrated that TBTCN-TDG combined with light treatment significantly inhibited SiHa cell proliferation, increased apoptosis, and activated immune responses by stimulating dendritic cells, macrophages, and NK cells, through enhanced NF-κB pathway signaling. In vivo, this targeted photosensitizer exhibited substantial therapeutic effects under laser excitation, as evidenced by TUNEL staining, which showed increased apoptosis in lesions. Immune analysis indicated that TBTCN-TDG enhanced NK cell viability and elevated the levels of pro-inflammatory cytokines under laser excitation, such as TNF-α, IFN-γ, and IL-6, confirming immune response activation. In conclusion, the combination of TBTCN-TDG and PDT effectively targets cells infected with HPV, enhances immune responses, and suppresses HPV infection. This suggests a novel therapeutic strategy for photodynamic immunotherapy in patients with cervical high-risk HPV infections.

In Situ Construction of Upconverting Nano-Bacteria Biohybrids via Biomimetic Mineralization for Synergistic Antitumor Phototherapy

Nano-bacteria biohybrids, which combine the advantages of nanomaterials and bacterial cells, have emerged as innovative platforms for cancer treatment. Integrated with optical nanomaterials, these biohybrids enable effective phototherapy. To overcome the challenge of limited tissue penetration by visible light in phototherapy, upconversion nanoparticles can be used to convert near-infrared (NIR) light into visible light, enabling the treatment of deep-seated tumors. In this study, we present a rapid method to fabricate upconversion nanoparticle-bacteria biohybrids (

Unveiling the Cytotoxic Potential of Quercetin-Loaded Magnetic Bacterial Bots against Cervical Cancer

Bacterial bots are potent vehicles in cancer theranostics where bacteria are used typically as cargos for drug delivery. However, living bacteria themselves may aid in their efficiency in killing the tissues. For example, living bacteria may be functionalized with magnetic and luminescent nanoparticles along with drugs in order to achieve the targeted delivery and release of payloads that would include the bacteria. In this study, we elucidate the synergistic impact of human-friendly living

Hybrid Membrane Camouflaged Chemodrug-Gene Nanoparticles for Enhanced Combination Therapy of Ovarian Cancer

Recently, cell membrane camouflaged nanoparticles (NPs) endowed with natural cellular functions have been extensively studied in various biomedical fields. However, there are few reports about such biomimetic NPs used to codeliver chemodrug and genes for synergistic cancer treatment up to now. Herein, we first prepare chemodrug-gene nanoparticles (Mito-Her2 NPs) by the electrostatic interaction coself-assembly of mitoxantrone hydrochloride (Mito) and human epidermal growth factor receptor-2 antisense oligonucleotide (Her2 ASO). Then, Mito-Her2 NPs are coated by a hybrid membrane (RSHM), consisting of the red blood cell membrane (RBCM) and the SKOV3 ovarian cancer cell membrane (SCM), to produce biomimetic chemodrug-gene nanoparticles (Mito-Her2@RSHM NPs) for combination therapy of ovarian cancer. Mito-Her2@RSHM NPs integrate the advantages of RBCM (e.g., good immune evasion capability and long circulation lifetime in the blood) and SCM (e.g., highly specific cognate recognition) together and improve the anticancer efficacy of Mito-Her2 NPs. The results show that Mito-Her2@RSHM NPs can be devoured by SKOV3 ovarian cancer cells and effectively degraded to release Her2 ASOs and Mito simultaneously. Her2 ASOs can inhibit the expression of endogenous Her2 genes and recover cancer cells' sensitivity to Mito, which ultimately led to a high apoptosis rate of 75.7% in vitro. Mito-Her2@RSHM NPs also show a high tumor suppression rate of 83.33 ± 4.16% in vivo without significant damage to normal tissues. In summary, Mito-Her2@RSHM NPs would be expected as a versatile and safe nanodrug delivery platform with high efficiency for chemo-gene combined cancer treatment.

Ultrabright NIR-IIb Fluorescence Quantum Dots for Targeted Imaging-Guided Surgery

Pioneering approaches for precise tumor removal involve fluorescence-guided surgery, while challenges persist, including the low fluorescence contrast observed at tumor boundaries and the potential for excessive damage to normal tissue at the edges. Lead/cadmium sulfide quantum dots (PbS@CdS QDs), boasting high quantum yields (QYs) and vivid fluorescence, have facilitated advancements in the second near-infrared window (NIR-II, 900-1700 nm). However, during fluorescent surgical navigation operations, hydrophilic coatings of these inorganic nanoparticles (NPs) guarantee biosafety; it also comes at the expense of losing a significant portion of QY and NIR-II fluorescence, causing heightened damage to normal tissues caused by cutting edges. Herein, we present hydrophilic core-shell PbS@CdS@PEG NPs with an exceptionally small diameter (∼8 nm) and a brilliant NIR-IIb (1500-1700 nm) emission at approximately 1600 nm. The mPEG-SH (MW: 2000) addresses the hydrophobicity and enhances the biosafety of PbS@CdS QDs.

pH-Thermo Dual-Responsive Polymeric Nanoparticles for Women’s Health: Dual Action Against Cervical and Ovarian Cancer Cells

The development of smart nanocarriers capable of responding to tumor-specific stimuli represents a promising strategy for improving therapeutic selectivity in oncology. In this work, we present a class of dual-responsive polymeric nanoparticles (NPs) engineered for precision drug delivery in gynecological cancers. Amphiphilic block copolymers of the type P(MAA)-

NIR-II Fluorescence Imaging for the Detection and Resection of Cancerous Foci and Lymph Nodes in Early-Stage Orthotopic and Advanced-Stage Metastatic Ovarian Cancer Models

The high mortality rate of ovarian cancer can be primarily attributed to late diagnosis and early lymph node (LN) metastasis. The anatomically deep-located ovaries own intricate anatomical structures and lymphatic drainages that compromise the resolution and sensitivity of near-infrared first-window (NIR-I) fluorescence imaging. Reported NIR-II imaging studies of ovarian cancer focused on late-stage metastasis detection via the intraperitoneal xenograft model. However, given the significant improvement in patient survival associated with early-stage cancer detection, locating tumors that are restricted within the ovary is equally crucial. We obtained the polymer nanoparticles with bright near-infrared-II fluorescence (NIR-II NPs) by nanoprecipitation of DSPE-PEG, one of the ingredients of FDA-approved nanoparticle products, and benzobisthiadiazole, an organic NIR-II dye. The one-step synthesis and safe component lay the groundwork for its clinical translation. Benefiting from the NIR-II emission (∼1060 nm), NIR-II NPs enabled a high signal-to-noise (S/N) ratio (13.4) visualization of early-stage orthotopic ovarian tumors with NIR-II fluorescence imaging for the first time. Imaging with orthotopic xenograft allows a more accurate mimic of human ovarian cancer origin, thereby addressing the dilemma of translating existing nanoprobe preclinical research by providing the nano-bio interactions with early local tumor environments. After PEGylation, the desirable-sized probe (∼80 nm) exhibited high lymphophilicity and relatively extended circulation. NIR-II NPs maintained their accurate detection of orthotopic tumors, tumor-regional LNs, and minuscule (<1 mm) disseminated peritoneal metastases simultaneously (with S/N ratios all above 5) in mice with advanced-stage cancer in real time ∼36 h after systematic delivery. With NIR-II fluorescence guidance, we achieved accurate surgical staging in tumor-bearing mice and complete tumor removal comparable to clinical practice, which provides preclinical data for translating NIR-II fluorescence image-guided surgery.

Reversal of Cisplatin Resistance in Ovarian Cancer by the Multitargeted Nanodrug Delivery System Tf-Mn-MOF@Nira@CDDP

Cisplatin (CDDP) is a widely used chemotherapeutic drug with proven efficacy for treating tumors. However, its use has been associated with severe side effects and eventually leads to drug resistance, thus limiting its clinical application in patients with ovarian cancer (OC). Herein, we aimed to investigate the success rate of reversing cisplatin resistance using a synthetic, multitargeted nanodrug delivery system comprising a Mn-based metal-organic framework (Mn-MOF) containing niraparib (Nira) and CDDP alongside transferrin (Tf) conjugated to the surface (Tf-Mn-MOF@Nira@CDDP; MNCT). Our results revealed that MNCT can target the tumor site, consume glutathione (GSH), which is highly expressed in drug-resistant cells, and then decompose to release the encapsulated Nira and CDDP. Nira and CDDP play a synergistic role in increasing DNA damage and apoptosis, exhibiting excellent antiproliferation, migration, and invasion activities. In addition, MNCT significantly inhibited tumor growth in tumor-bearing mice and exhibited excellent biocompatibility without side effects. Furthermore, it depleted GSH, downregulated multidrug-resistant transporter protein (

Next-Generation Femtech: Urine-Based Cervical Cancer Diagnosis Using a Fluorescent Biothiol Probe with Controlled Smiles Rearrangement

Cervical cancer screening is a crucial field of femtech (female technology). In this work, we disclosed a new femtech solution─a simple, straightforward, and on-site applicable urine-based cervical cancer diagnostic method using a fluorescent biothiol probe. Our newly developed nitrobenzene-based fluorescent probe, named

Surgery-Guided Removal of Ovarian Cancer Using Up-Converting Nanoparticles

Ovarian cancer survival and the recurrence rate are drastically affected by the amount of tumor that can be surgically removed prior to chemotherapy. Surgeons are currently limited to visual inspection, making smaller tumors difficult to be removed surgically. Enhancing the surgeon's ability to selectively remove cancerous tissue would have a positive effect on a patient's prognosis. One approach to aid in surgical tumor removal involves using targeted fluorescent probes to selectively label cancerous tissue. To date, there has been a trade-off in balancing two requirements for the surgeon: the ability to see maximal tumors and the ability to identify these tumors by eye while performing the surgery. The ability to see maximal tumors has been prioritized and this has led to the use of fluorophores activated by near-infrared (NIR) light as NIR penetrates most deeply in this surgical setting, but the light emitted by traditional NIR fluorophores is invisible to the naked eye. This has necessitated the use of specialty detectors and monitors that the surgeon must consult while performing the surgery. In this study, we develop nanoparticles that selectively label ovarian tumors and are activated by NIR light but emit visible light. This potentially allows for maximal tumor observation and real-time detection by eye during surgery. We designed two generations of up-converting nanoparticles that emit green light when illuminated with NIR light. These particles specifically label ovarian tumors most likely via tumor-associated macrophages, which are prominent in the tumor microenvironment. Our results demonstrate that this approach is a viable means of visualizing tumors during surgery without the need for complicated, expensive, and bulky detection equipment. Continued improvement and experimentation could expand our approach into a much needed surgical technique to aid ovarian tumor removal.

Synergy between Intraperitoneal Aerosolization (PIPAC) and Cancer Nanomedicine: Cisplatin-Loaded Polyarginine-Hyaluronic Acid Nanocarriers Efficiently Eradicate Peritoneal Metastasis of Advanced Human Ovarian Cancer

Intra-abdominal dissemination of peritoneal nodules, a condition known as peritoneal carcinomatosis (PC), is typically diagnosed in ovarian cancer patients at the advanced stages. The current treatment of PC consists of perioperative systemic chemotherapy and cytoreductive surgery, followed by intra-abdominal flushing with solutions of chemotherapeutics such as cisplatin and oxaliplatin. In this study, we developed cisplatin-loaded polyarginine-hyaluronic acid nanoscale particles (Cis-pARG-HA NPs) with high colloidal stability, marked drug loading efficiency, unimpaired biological activity, and tumor-targeting ability. Injected Cis-pARG-HA NPs showed enhanced antitumor activity in a rat model of PC, compared to injection of the free cisplatin drug. The activity of Cis-pARG-HA NPs could even be further improved when administered by an intra-abdominal aerosol therapy, referred to as pressurized intraperitoneal aerosol chemotherapy (PIPAC). PIPAC is hypothesized to ensure a more homogeneous drug distribution together with a deeper drug penetration into peritoneal tumor nodules within the abdominal cavity. Using fluorescent pARG-HA NPs, this enhanced nanoparticle deposit on tumors could indeed be observed in regions opposite the aerosolization nozzle. Therefore, this study demonstrates that nanoparticles carrying chemotherapeutics can be synergistically combined with the PIPAC technique for IP therapy of disseminated advanced ovarian tumors, while this synergistic effect was not observed for the administration of free cisplatin.

Indicator Displacement Assay Inside Dye-Functionalized Covalent Organic Frameworks for Ultrasensitive Monitoring of Sialic Acid, an Ovarian Cancer Biomarker

Identifying biomolecules for disease diagnosis requires simple, accurate, and reliable analytical techniques. Multiple signal transduction pathways have promoted the development of various biological analysis systems. However, most systems are largely limited by a single mechanism or model analysis, which can easily lead to false-positive/negative results. Herein, we report a covalent organic framework (COF) (

Construction of Dynamic Hydrogel Inducing Effective and Selective 5-Fluorouracil Monotherapy against Cervical Cancer Cells

The severe side effects of systemic chemotherapy for cervical cancer encourage the use of topical intravaginal drug delivery systems. 5-fluorouracil, 5-FU, is an anticancer drug accepted in clinical use in the cancer therapy of colorectal, gastric, and hepatocellular carcinoma. However, it shows low activity against cervical cancer cells (HeLa) and thus requires the usage of additional drugs to support the therapy, which is associated with side effects. We report on the polyglycidol/polyacrylamide-based hydrogel carrier providing effective monotherapy against cervical cancer cells, HeLa with 5-FU, along with a neutral effect on normal cells, HMEC-1. The use of hyperbranched polyglycidol modified with aryl groups, i.e., phenylurethane, 1,4-biphenylurethane, and benzoyl ester, respectively, to enhance the solubility of 5-FU in the aqueous medium ensured the drug's efficacy and selectivity against Hela cells after 48 h at a low dose. Crucially, the cross-linking of drug-loaded aryl-enriched polyglycidol with an acrylamide copolymer bearing 2-acrylamidephenylboronic acid induced the anticervical cancer activity reducing the time required for complete cervical cancer cell death to 24 h. An in vitro study showed that boronic acid moieties are responsible for the promotion of anticervical cancer activity with 5-FU. Reported hydrogels' structure based on reversibly cross-linked aryl-enriched HbPGLs provides the self-healing properties of the network crucial for the formation of the continuous layer of formulation ensuring the delivery of the drug to the afflicted area of the covered tissue. Among tested hydrogels, the system constructed from HbPGL which linear constitutional units were modified with benzoyl ester or and phenylurethane moieties at approximately 45 mol % showed the highest drug permeability through the STRAT-M model membrane. This study demonstrates the direction of the synthetic design of the hydrogel carrier of 5-FU assuring safe monotherapy of cervical cancer cells, avoiding side effects typical for combinatory therapies.