Colloids and Surfaces B: Biointerfaces

Disrupting Cdc42 activation-driven filopodia formation with low-intensity ultrasound and microbubbles: A novel strategy to block ovarian cancer metastasis

Metastasis is a primary cause of mortality and treatment failure in ovarian cancer, with limited effective therapeutic strategies. Low-intensity ultrasound (LIUS) and microbubbles (MBs) has been demonstrated as an adjunctive technique capable of enhancing drug delivery and suppressing tumor metastasis. However, the underlying mechanisms remain incompletely understood. In this study, we aimed to investigate whether LIUS + MBs alone could suppress tumor metastasis and to explore its mechanism of action through disruption of the cytoskeletal remodeling in filopodia, an essential structure in the early stages of cancer cell dissemination. Based on cell-based experiments to determine the optimal parameters, our results showed LIUS + MBs significantly inhibited the migration and invasion of ovarian cancer cells. In vivo, LIUS + MBs treatment markedly suppressed the overall metastasis in the orthotopic ovarian cancer model, and in both the intraperitoneal and hematogenous metastatic models established by injecting pretreated cells. Morphologically, such treatment led to a notable reduction in the length and number of filopodia, while the number of lamellipodia remained unaffected. At the molecular level, LIUS + MBs disturbed filopodia formation and the metastatic potential of ovarian cancer cells by suppressing the activation of Cdc42, a key regulator of cytoskeletal dynamics. The inhibitory effect was reversed by the overexpression of Cdc42CA. Further proteomic and bioinformatics analysis implied that LIUS + MBs may reduce Cdc42 activity by upregulating the expression of GTPase-activating proteins (GAPs). Our research provides novel insight into the mechanism by which LIUS + MBs can inhibit tumor metastasis, highlighting its role in disturbing the Cdc42-mediated cytoskeletal remodelling of filopodia.

Apatinib-loaded silicate nanoparticles coated with macrophage membranes and PD-1 antibody for enhanced chemo-immunotherapy in ovarian cancer via VEGFR2 and PD-1 dual inhibition

Ovarian cancer remains one of the most challenging malignancies to treat due to its aggressive nature and resistance to conventional therapies. In this study, we developed a nanoparticle-based system (Apa@SiO

Thermo-sensitive PLGA-PEG-PLGA hydrogel for sustained release of EGF to inhibit cervical cancer recurrence

Overexpression of epidermal growth factor receptor (EGFR) in cancer is a key cause of recurrence of cervical cancer (CC). Although the EGF-EGFR pathway has been studied for decades, preventing tumor growth and recurrence caused by peripheral EGF remains a great challenge. In this work, a strategy is proposed to reduce the stimulation of high concentration EGF on tumor growth by using a thermo-sensitive hydrogel. The hydrogel is a triblock copolymer composed of polyethylene glycol (PEG) and poly (lactide glycolide) (PLGA). Based on the excellent temperature sensitivity, carrier capacity, swelling property and biocompatibility, the hydrogel can absorb the liquid around the tumor by injection and release EGF continuously at low concentration. The inhibitory effect of hydrogel on tumor growth is fully confirmed by an implanted tumor mouse model with human cervical cancer cell lines (HeLa) using triple-immunodeficient NCG mice. Compared with free EGF, the EGF-loaded hydrogel can hardly induce surface plasmon resonance (SPR) response, which proves that hydrogel can effectively weaken cytoskeleton rearrangement and inhibit cell migration by continuously releasing low concentration EGF. In addition, the EGF-loaded hydrogel can reduce cell proliferation by delaying the progress of cell cycle progression. Taken together, the hydrogel can effectively protect tumor microenvironment from the stimulation of high concentration EGF, delay cancer cellular processes and tumor growth, and thus providing an approach for inhibiting tumor recurrence of CC.

Oxygen vacancy engineering of TiO2 nanosheets for enhanced photothermal therapy against cervical cancer in the second near-infrared window

Cervical cancer is the most common and deadly female cancer on the worldwide scale. Considering that the conventional surgery treatment and chemotherapy would cause certain side effects, photothermal therapy (PTT) possesses desired therapeutic efficiency and insignificant side effects against cervical cancer. However, the lack of efficient and safe photothermal agents that operate in the second near-infrared (NIR-II) window is a main obstacle hindering the clinical transformation of PTT. Titanium dioxide (TiO

An all-graphene quantum dot Förster resonance energy transfer (FRET) probe for ratiometric detection of HE4 ovarian cancer biomarker

Ovarian cancer (OVC), the most lethal form of all gynecological cancers, is a big threat to women's health. Late diagnosis at the advanced stages is one of the major reasons for the ovarian cancer-related deaths. Conventionally, the up-regulated proteins CA125 (cancer antigen 125) and HE4 (human epididymis protein 4) are used as biomarkers to diagnose the OVC malignancies. The lack of sensitivity/specificity and the false-positive results create complexity in the diagnostic process. With specificity over 90 %, HE4 is suitable for diagnosing ovarian cancer. Herein, we have developed an ultrasensitive all-graphene quantum dot (GQD) Förster resonance energy transfer (FRET) probe for the ratiometric detection of HE4 biomarker. A set of two GQD samples were solvothermally prepared and then analyzed by the morphological, structural, and photophysical characterization. One GQD sample exhibited a strong green emission, peaked at around 515 nm, while the other GQD sample displayed a strong red emission with maximum at around 615 nm. The good spectral overlap between the emission and excitation spectra of the green and red GQDs, respectively, all allowed us to consider them for the design of FRET-based probe. The green and red-emitting GQDs were conjugated with HE4 antibody and used as donor and acceptor, respectively for the ratiometric sensing of HE4 ovarian cancer biomarker. The all GQD FRET probe was able to detect as low as 4.8 pM, along with a large dynamic detection range up to 300 nM. The selectivity and interference effect of the developed FRET probe was also investigated against different protein combinations.

Gold nanorods conjugated with biocompatible zwitterionic polypeptide for combined chemo-photothermal therapy of cervical cancer

Combined chemo-photothermal therapy of gold nanorods (GNRs) for cancer treatment shows better therapeutic efficiency than mono-chemotherapy, which has gained worldwide interests of scientists and clinician in both laboratory and clinic application. However, high cytotoxicity, declined delivery efficiency, and unsatisfactory therapy effect of the GNRs are still challenging in anti-cancer treatment. Herein, a series of pH-sensitively zwitterionic polypeptide conjugated GNRs were synthesized via a gold-thiol interaction for combination of chemo-photothermal therapy in cervical cancer treatment. The acid-labile hydrazone bond was utilized to incorporate the doxorubicin (DOX) for pH-sensitive drug release under tumoral environment. The as prepared GNRs conjugates demonstrated pH-triggered surface charge conversion from negative to positive when transporting from blood circulation to tumor extracellular environment, which can facilitate the cellular uptake via electrostatic interaction. After cellular internalization, the drug release was promoted by cleavage of the hydrazone in GNRs conjugates under cancer intracellular acid environment. As the effective near-infrared (NIR) photothermal materials, the as prepared GNRs conjugates can absorb NIR photo energy and convert it into heat under irradiation, which can efficiently kill the tumor cells. In cell assay, the GNRs conjugates displayed excellent biocompatibility against normal cell, enhanced cancer cell uptake, and remarkable cancer cell killing effects. In HeLa tumor-bearing mice, the GNRs conjugates demonstrated enhanced tumor inhibition efficacy by combination of chemo-photothermal therapy.

A cationic amino acid polymer nanocarrier synthesized in supercritical CO2 for co-delivery of drug and gene to cervical cancer cells

The present study was undertaken to investigate the ability of a drug curcumin-loaded polymer to inhibit the growth of cervical cancer cells by enhancing the anti-cancer efficiency of curcumin. We synthesized poly(methacryloyl beta-alanine) (PMBA) as a nanocarrier by radical polymerization in supercritical CO

ROS-responsive supramolecular antimicrobial peptides-based nanoprodrugs for cervical cancer therapy

Although antimicrobial peptides (AMPs) as a promising natural drugs can efficiently inhibit cervical cancer, poor bioavailability, low tumor selectivity, and non-selective toxicity still hinder its further application in vivo. In order to effectively address these challenges, we have developed a reactive oxygen species (ROS)-responsive targeting nanoprodrug designed for selective therapy of cervical cancer. Such nanoprodrugs (CEC-OxbCD) are fabricated by the supramolecular self-assembly of the modified β-cyclodextrin (β-CD) and AMPs. Antimicrobial peptide, CecropinXJ (CEC), is a cationic antibacterial peptide isolated from 3rd instar larvae of Bombyx mori from Xinjiang, China. OxbCD is an oxidation-responsive β-cyclodextrin material. CEC-OxbCD were synthesized using the nanoprecipitation/self-assembly method. Subsequently, the particle size distribution, morphology, drug loading efficiency, and release behaviour of CEC-OxbCD were characterised. In vitro and in vivo anti-cancer activities were also evaluated. Nanoprodrugs can be effectively disassembled under stimuli of the tumor- endogenous ROS, resulting in a rapid and on-demand release of antimicrobial peptides (AMPs) with a release rate of 90 %. Furthermore, both in vitro and in vivo experimental results demonstrate that our nanoprodrugs exhibit remarkable therapeutic efficacy against cervical cancer. This work not only provides an effective and promising therapeutic strategy for cervical cancer, but also explores a novel application for AMPs.

Preparation of novel Mn-doped Ti-based organic frameworks for the sonodynamic therapy of serous ovarian carcinoma

Serous ovarian carcinoma (SOC) is distinguished by marked invasiveness, early dissemination and rapid drug resistance, creating an urgent demand for non‑cross‑resistant alternative therapies. Consequently, the exploration of minimally invasive yet highly effective treatment modalities has become a central research priority. In the present work, a heterobimetallic metal-organic frameworks (MOFs) sonosensitizer, namely Mn‑MX@MIL‑125(Ti), was synthesized by introducing manganese(II) ions into MXene-trussed Ti‑based organic frameworks. The obtained Mn-MX@MIL-125(Ti) exhibited high specific surface area, tunable mesoporous, and abundant metal sites, which collectively conferred excellent catalytic activity. Through a series of tests, it was found that Mn‑MX@MIL‑125(Ti) enhanced the generation of reactive oxygen species (ROS) under low‑intensity ultrasound. For the SK-OV-3 cells, the PEG ylated Mn-MX@MIL-125(Ti) displayed good biocompatibility, but upon ultrasound irradiation, it accomplished half‑maximal inhibitory concentration (IC₅₀) of 27.5 µg mL⁻¹ . And, the pronounced decline in mitochondrial membrane potential indicated that it was the ROS‑mediated mitochondrial damage to effectively curtail tumour proliferation. Besides, in subcutaneous SOC murine model, the tumour‑inhibition rate of 83 % was achieved without discernible systemic toxicity. These results highlight that the Mn-MX@MIL-125(Ti) as a promising bimetallic sonosensitizer is capable of efficiently suppressing the SOC via ultrasound-induced ROS generation.

Folate-targeted Pluronic-chitosan nanocapsules loaded with IR780 for near-infrared fluorescence imaging and photothermal-photodynamic therapy of ovarian cancer

Herein, we report the fabrication of a nanotherapeutic platform integrating near-infrared (NIR) imaging with combined therapeutic potential through photodynamic (PDT) and photothermal therapies (PTT) and recognition functionality against ovarian cancer. Owing to its NIR fluorescence, singlet oxygen generation and heating capacity, IR780 iodide is exploited to construct a multifunctional nanosystem for single-wavelength NIR laser imaging-assisted dual-modal phototherapy. We opted for loading IR780 into polymeric Pluronic-F127-chitosan nanoformulation in order to overcome its hydrophobicity and toxicity and to allow functionalization with folic acid. The obtained nanocapsules show temperature-dependent swelling and spectroscopic behavior with favorable size distribution for cellular uptake at physiological temperatures, improved fluorescence properties and good stability. The fabricated nanocapsules can efficiently generate singlet oxygen in solution and are able to produce considerable temperature increase (46 °C) upon NIR laser irradiation. Viability assays on NIH-OVCAR-3 cells confirm the successful biocompatibilization of IR780 by encapsulating in Pluronic and chitosan polymers. NIR fluorescence imaging assays reveal the ability of folic-acid functionalized nanocapsules to serve as intracellular contrast agents and demonstrate their active targeting capacity against folate receptor expressing ovarian cancer cells (NIH-OVCAR-3). Consequently, the targeted nanocapsules show improved NIR laser induced phototherapeutic performance against NIH-OVCAR-3 cells compared to free IR780. We anticipate that this class of nanocapsules holds great promise as theranostic agents for application in image-guided dual PDT-PTT and imaging assisted surgery of ovarian cancer.

Smart phase-change CuS@Vk3@LA nanoplatform enables tumor-selective, synergistic chemodynamic and photothermal therapy

Ovarian cancer therapy remains limited by high recurrence and unsatisfactory responses to current treatments. Here, we developed a multifunctional nanoplatform (CuS@Vk3@LA) that integrates photothermal therapy (PTT), chemodynamic therapy (CDT), and near-infrared (NIR)-controlled drug release. The hollow CuS core serves as both a NIR absorber and a Fenton-like catalyst, enabling simultaneous heat generation and hydroxyl radical production. Uniquely, vitamin K3 (Vk3) was incorporated to enhance endogenous H₂O₂ levels through NQO1-mediated redox cycling, thereby overcoming the substrate shortage that restricts conventional CDT. To prevent premature leakage, lauric acid (LA) was introduced as a thermosensitive phase-change shell, which melts under mild hyperthermia to trigger on-demand release. This rational design establishes a dual oxidative-stress mechanism-ROS amplification and GSH depletion-resulting in synergistic tumor cell killing. Systematic evaluations demonstrated excellent colloidal stability, biocompatibility, and tumor-selective accumulation. In vivo, CuS@Vk3@LA achieved pronounced tumor growth inhibition with minimal systemic toxicity. Collectively, this study provides a precise and safe nanotherapeutic strategy that combines catalytic amplification with photothermal activation, showing strong translational potential for ovarian cancer treatment.

Anti-PD-L1 immobilization on Fe₃O₄ nanocluster-coated AuNR through terpyridine–gadolinium coordination for multimodal imaging and synergistic tumor therapy

Functionalized nanoparticles offer a versatile nanomedicine platform for engineering stimulus-responsive, theranostic drug delivery systems to enhance tumor diagnosis and treatment. Herein, we present the development of a stimulus-responsive Fe₃O₄@AuNR nanotherapeutic platform functionalized with anti-PD-L1, which enables antibody and dual drug loading, tumor-specific controlled release, image-guided combination therapy, and synergistic enhancement of antitumor efficacy. As a biomarker of senescence and tumor progression, β-galactosidase enables 5-FUR-β-Gal prodrug activation, contributing to targeted therapeutic strategies for ovarian cancer. The anti-PD-L1-functionalized Fe₃O₄@AuNR drug delivery system combines chemotherapy, targeted therapy, and photothermal therapy, while simultaneously enabling fluorescence imaging and MRI of tumor tissues, thus providing a synergistic theranostic platform with promising clinical applicability.

Metallic-based phthalocyanine nanoemulsions for photodynamic purging of ovarian tissue in leukemia patients

For cancer patients with a high risk of ovarian tissue metastasis, ovarian autotransplantation is not advised due to the potential spread of malignant cells. Ex vivo purging of ovarian fragments may offer a more suitable alternative for fertility restoration. Eradicating malignant cells should be done selectively without affecting follicles or ovarian stromal cells (SCs). As a clinically licensed method, photodynamic therapy (PDT) is a minimally invasive treatment to destroy cancer cells. This study evaluates the effectiveness of nanoemulsions (NE) containing two phthalocyanine photosensitizers; aluminum (III) phthalocyanine (AlPc) and zinc (II) phthalocyanine (ZnPc) in eliminating cancer cells. Human leukemic malignant (HL-60) and ovarian stromal cells (SCs) were treated with AlPc/ZnPc loaded NEs with or without diode laser irradiation. HL-60 leukemia cells in 2D culture were eliminated by treatment with 10 nM AlPc-NE or 0.1 µM ZnPc-NE, while no toxicity was observed in SCs. In 3D culture models, although the cells showed more resistance to the NEs as a result of limited oxygen and photosensitizer penetration, the treatment remained selective for cancer cells. These approaches have the potential to eliminate malignant cells from ovarian tissue fragments.

pH/glutathione-responsive theranostic nanoprobes for chemoimmunotherapy and magnetic resonance imaging of ovarian cancer cells

The integration of immunotherapy and standard chemotherapy holds great promise for enhanced anticancer effects. In this study, we prepared a pH- and glutathione (GSH)-sensitive manganese-doped mesoporous silicon (MMSNs) based drug delivery system by integrating paclitaxel (PTX) and anti-programmed cell death-ligand 1 antibody (aPD-L1), and encapsulating with polydopamine (PDA) for chemoimmunosynergic treatment of ovarian cancer cells. The nanosystem was degraded in response to the tumor weakly acidic and reductive microenvironment. The Mn

Mesoporous silica-coated gold nanorod grafted with cisplatin prodrug on the surface enhances radiotherapy for cervical cancer via triple-strategy approach

Concurrent radio-chemotherapy remains the standard treatment for cervical cancer, but its efficacy is limited by tumor hypoxia and enhanced DNA repair in cancer cells. To address these issues, mesoporous silica (MSN)-coated gold nanorod (Au NR) grafted with cisplatin prodrug (MDDP) on the surface and O

Galectin-1-targeted theranostic nanoprobe for multimodal imaging and photothermal therapy in cervical cancer lymph node metastases

Accurately evaluating lymph node (LN) status is essential for cervical cancer staging and making treatment decisions. However, the current preoperative imaging modalities for diagnosing LN metastasis in patients with cervical cancer are suboptimal, and the existing radiochemotherapy methods lack specificity, which leads to increased toxicity and side effects. To overcome these limitations, we aimed to develop a theranostic strategy for LN metastases with a galectin-1-targeted nanoprobe for dual-modal magnetic resonance imaging (MRI)/near-infrared (NIR) imaging and photothermal therapy (PTT). The PEG@MnPb-IR820 nanoparticles were synthesized through an integrated approach combining microemulsion, thin-film hydration, and esterification coupling methods. The nanoparticles were synthesized and characterized for their physicochemical properties and biosafety. After extensive in vitro and in vivo experiments, the TDG@PMI NPs demonstrated low biological toxicity, excellent stability, and a diameter of 74 nm, which is suitable for LN accumulation. With effective MRI and NIR imaging guidance, this nanoprobe displayed outstanding anticancer activity in tumors and metastatic sentinel LNs upon single NIR laser irradiation by inducing mitochondrial apoptosis in tumor cells.

Floxuridine-chlorambucil conjugate nanodrugs for ovarian cancer combination chemotherapy

Due to no specific symptoms and lack of early diagnosis for ovarian cancer, most diagnosed patients are often in the terminal stage resulting that tumor tissue is unable to be resected completely by operation. So postoperative chemotherapy has become an important and indispensable treatment procedure for them. Up to date, it remains a challenge to treat ovarian cancer by an effective chemotherapy strategy. Recently, the strategy of ADDC has been regarded as a highly effective chemotherapy strategy to treat various cancers without any drug carriers. Here a novel ADDC is synthesized by linking a water-soluble antitumor drug floxuridine (Fud) and a water-insoluble antitumor drug chlorambucil (Cb) through the esterification. Then the Fud-Cb conjugate can form stable nanodrugs in water with an average size around 103.0 nm through molecular self-assembly. After internalization of cells, the ester bonds in nanodrugs can be degraded to release free Fud and Cb at a fixed ratio under the intracellular acid conditions, which exhibits the high synergistic effect on ovarian cancer cells. The cytotoxicity test results show that Fud-Cb nanodrugs can efficiently inhibit the growth of ovarian cancer cells. The apoptosis data exhibit that the cell necrotic and apoptotic rate treated with Fud-Cb nanodrugs is about 73.7 % and 18.76 % within 24 h. These results suggest that Fud-Cb nanodrugs based on ADDC strategy can effectively enhance synergistic anticancer efficacy to ovarian cancer.

Polymeric nanoparticles-siRNA as an emerging nano-polyplexes against ovarian cancer

Ovarian cancer (OC) is considered fifth-deadliest cancer globally responsible for high mortality in women. As the conventional therapeutic and diagnostic approaches are ineffective in increasing the survival rates of advanced staged patients by more than 5 years, OC has resulted in high morbidity and mortality rates over the last two decades. As a result, there is a dire need for innovative treatment approaches to address the issues. RNAi and nanotechnology can be considered the most appropriate strategies that can be used to improve OC therapy and help circumvent the chemo-resistance. siRNA is considered highly successful in facilitating the knockdown of specific genes on entering the cytosol when administered in-vivo via inhibiting the mRNA expression responsible for translation of those specific genes through the mechanism called RNA interference (RNAi). However, the primary barrier of utmost importance in the clinical efficacy of employed siRNA for the treatment of OC is the systemic distribution to the targeted site from the administration site. As a result, nanoparticles are constructed to carry the siRNA molecules inside them to the targeted site by preventing serum degradation and enhancing the serum stability of administered siRNA. The present review assesses the developments made in the polymeric-based nanoparticle siRNA delivery for targeting particular genes involved in the prognosis of ovarian cancers and surpassing the chemo-resistance and thus improving the therapeutic potentials of administered agents.

Active targeting liposome-PLGA composite for cisplatin delivery against cervical cancer

Cisplatin (Cis) is a widely used chemotherapeutic drug for cancer treatment. However, toxicities and drug resistance limit the use of cisplatin. This study was aimed to improve cisplatin delivery using a targeting strategy to reduce the toxicity. In the present study, combinations of poly lactic-co-glycolic acids (PLGA) and liposomes were used as carriers for cisplatin delivery. In addition, to target the nanoparticle towards tumor cells, the liposome was conjugated with Avastin®, an anti-VEGF antibody. Cisplatin was loaded into PLGA using the double emulsion solvent evaporation method and further encapsulated in an Avastin® conjugated liposome (define herein as L-PLGA-Cis-Avastin®). Their physicochemical properties, including particle size, ζ-potential, encapsulation efficiency and drug release profiles were characterized. In addition, a study of the efficiency of tumor targeted drug delivery was conducted with cervical tumor bearing mice via intravenous injection. The therapeutic effect was examined in a 3D spheroid of SiHa cell line and SiHa cells bearing mice. The L-PLGA-Cis-Avastin® prompted a significant effect on cell viability and triggered cytotoxicity of SiHa cells. A cell internalization study confirmed that the L-PLGA-Cis-Avastin® had greater binding specificity to SiHa cells than those of L-PLGA-Cis or free drug, resulting in enhanced cellular uptake. Tumor targeting specificity was finally confirmed in xenograft tumors. Taken together, this nanoparticle could serve as a promising specific targeted drug for cervical cancer treatment.

Ruthenium(II)-curcumin liposome nanoparticles: Synthesis, characterization, and their effects against cervical cancer

Ruthenium complexes have increased the scope for improvement in current cancer treatment by replacing platinum-based drugs. However, to reduce metal-associated toxicity, a biocompatible flavonoid, such as curcumin, is indispensable, as it offers uncompensated therapeutic benefits through formation of complexes. In this study, we synthesized metal-based flavonoid complexes using ruthenium(II) and curcumin by adopting a convenient reflux reaction, represented as Ru-Cur complexes. These complexes were thoroughly characterized using