Anticancer Drug Doxorubicin Research Articles

A polysaccharide-based hydrogel platform for tumor spheroid production and anticancer drug screening

Extracellular matrix mimics are still needed to grow cancer cells in 3D environments and study their evolution in vitro while precisely controlling relevant features. Most models currently use collagen, which is biomimetic but degrades quickly, or artificial polymers, which can be chemically modified but remain stiff. Herein we introduced a soft, non-adhesive, and resistant hydrogel platform for tumor spheroid production using a polysaccharide-based formulation. To ensure micro-structuring of the hydrogel and enable spheroid formation, 3D printed molds consisting of a network of 200-µm-diameter micropillars were used to generate microstructured hydrogel constructs that fit into a multi-well plate. This platform was validated for drug testing using three cancer cell lines (A673, MCF7 and U87) and 2 anticancer drugs (doxorubicin and paclitaxel). Drug response was assessed through bright-field microscopy monitoring and viability measurements after 48 h of treatment. This study validates the use of pullulan-dextran hydrogels for spheroid formation, combined with in situ drug screening.

Evaluating the Drug Delivery Capacity of 3D Coordination Polymer for Anticancer Drugs.

We synthesized {[Cd2(dTMP)2(4,4'-azpy)2(H2O)2] ⋅ 3(O)}n a novel three-dimensional metal nucleotide coordination polymer (CP-1). An assessment of the CP-1 binding affinity for anticancer drugs was conducted using molecular dynamic simulations. The virtual screening results depict that CP-1 has a lot of potential for encapsulating the anthracycline anticancer drug doxorubicin (DOX). It hasn't yet been investigated how to accomplish high loading capacity, efficiency, and controlled release of DOX in dTMP-based 3D metal coordination polymers. Utilizing DOX as a drug model and our system as a drug-loading vehicle, we used UV-visible and circular dichroism titrations to examine the effects of its encapsulation and release. The mechanism of drug loading and release was investigated through pH-responsive behavior by adjusting the pH value to 8, 7, 6, and 5. The results indicate the CP-1 has a robust affinity for DOX at pH 7, which facilitates its loading on 3D porous coordination polymer. However, the maximum cumulative drug release of 87.11 % was observed at pH 5. The higher correlation coefficient (R2) was obtained at pH 5 with the Higuchi equation. It indicated that the drug released was primarily controlled with the diffusion mechanism. The CP-1 polymer's ability to encapsulate DOX while also permitting a possible controlled-release mechanism is confirmed by the combined insights from the experimental findings, energy graphs, RMSD analysis, and radius of gyration (Rg) data from MD simulations.

Novel Bioorthogonal Theranostic Scaffold Enables on-Target Drug Release and Real Time Monitoring In Vivo.

Bioorthogonal chemistry-based prodrug strategy features spatiotemporally controlled release of therapeutic agent and/or imaging probe. However, the integration of diagnosis and therapy into a single molecule paired with a single bioorthogonal trigger remains a challenge. In this study, we devised a novel bioorthogonal theranostic scaffold amenable to the conjugation of various targeting agent and click-to-release reaction with the bioorthogonal prodrug to enable targeted drug liberation with concomitant fluorescence emission. Such one-stone-three-birds scaffold consists of a new fluorophore phenanthrodioxine (PDO) linked with a fluorescence masking group, tetrazine (Tz) which serves as a dual switch for the activation of fluorophore and drug. Further installation of a warhead of phenylboronic acid (PBA) ensures the targeted accumulation of the resultant PBA-PDO-Tz conjugate in tumor cells, thereby achieving on-demand activation of trans-cyclooctene-caged anticancer drug Doxorubicin with real-time monitoring and on-target cytotoxicity in live cells and an A549 xenograft mouse model. The targeted single trigger-dual response scaffold holds promise for precise theranostics applications in vivo.

Preparation, Coating, and Multimodal Therapeutic Properties of an Anticancer System Based on UiO-66(Ce).

UiO-66(Ce) was prepared from cerium metal, which could trigger Fenton-like reactions. A system DOX@UiO-66(Ce)@TA-Fe was constructed by coating a metal polyphenol layer (TA-Fe) on the surface of DOX@UiO-66(Ce), which was loaded with the anticancer drug doxorubicin hydrochloride (DOX). It could produce reactive oxygen species to realize chemodynamic therapy and show stimuli-responsive drug release behaviors to realize chemotherapy. In addition, the system displayed biocompatibility to normal cells (L929 cells) and toxicity to cancer cells (MCF-7 cells), implying an ideal effect for multimodal cancer therapy.

Enhancing hepatocellular carcinoma therapy with DOX-loaded SiO2 nanoparticles via mTOR-TFEB pathway autophagic flux inhibition

Chemotherapeutic drugs often fail to provide long-term efficacy due to their lack of specificity and high toxicity. To enhance the biosafety and reduce the side effects of these drugs, various nanocarrier delivery systems have been developed. In this study, we loaded the anticancer drug doxorubicin (DOX) and an MRI contrast agent into silica nanoparticles, coating them with pH-responsive and tumor cell-targeting polymers. These polymers enable the carrier to achieve targeted delivery and controlled drug release in acidic environments. This integrated diagnostic and therapeutic strategy successfully achieved both the diagnosis and treatment of liver cancer. Additionally, we demonstrated that the nanocarrier inhibits autophagic flux in liver cancer cells by targeting the autophagy-lysosome pathway and regulating the nuclear translocation of TFEB, thereby promoting tumor cell death. This novel diagnostic-integrated nanocarrier is expected to be a promising tool for targeted liver cancer treatment.

Development of Mg-Alginate Based Self Disassociative Bio-Ink for Magnetic Bio-Patterning of 3D Tumor Models.

Alginate forms a hydrogel via physical cross-linking with divalent cations. In literature, Ca2+ is mostly utilized due to strong interactions but additional procedures are required to disassociate Ca-alginate hydrogels. On the other hand, Mg-alginate hydrogels disassociate spontaneously, which might benefit certain applications. This study introduces Mg-alginate as the main component of a bio-ink for the first time to obtain 3D tumor models by magnetic bio-patterning technique. The bio-ink contains magnetic nanoparticles (MNPs) for magnetic manipulation, Mg-alginate hydrogel as a sacrificial material, and cells. The applicability of the methodology is tested for the formation of 3D tumor models using HeLa, SaOS-2, and SH-SY5Y cells. Long-term cultures are examined by Live/dead and MTT analysis and revealed high cell viability. Subsequently, Collagen and F-actin expressions are observed successfully in 3D tumor models. Finally, the anti-cancer drug Doxorubicin (DOX) effect is investigated on 3D tumor models, and IC50 values is calculated to assess the drug response. As a result, significantly higher drug resistance is observed for bio-patterned 3D tumor models up to tenfold compared to 2D control. Overall, Mg-alginate hydrogel is successfully used to form bio-patterned 3D tumor models, and the applicability of the model is shown effectively, especially as a drug screening platform.

Physical, biochemical, and biological characterization of olive-derived lipid nanovesicles for drug delivery applications

Extracellular vesicles (EVs) have shown great promise as drug delivery system (DDS). However, their complex and costly production limit their development for clinical use. Interestingly, the plant kingdom can also produce EV-like nanovesicles that can easily be isolated and purified from a large quantity of raw material at a high yield. In this study, olive-derived nanovesicles (ODNVs) were isolated from raw fruits using serial centrifugations and their physical and biological features characterized to demonstrate their promising potential to be used as a DDS. Nanotracking particle analysis indicated an average size of 109.5 ± 3.0 nm and yield of 1012 ODNVs/mL for the purest fraction. Microscopy imaging, membrane fluidity assay and lipidomics analysis showed the presence of a rich lipid bilayer that significantly varied between different sources of ODNVs but showed a distinct signature compared to human EVs. Moreover, ODNVs were enriched in PEN1 and TET8 compared to raw fruits, suggesting an extracellular origin. Interestingly, ODNVs size and yield stayed unchanged after exposure to high temperature (70 °C for 1 h), wide pH range (5–10), and 50–100 nm extrusion, demonstrating high resistance to physical and chemical stresses. This high resistance allowed ODNVs to stay stable in water at 4 °C for a month, or with the addition of 25 mM trehalose for long-term freezing storage. Finally, ODNVs were internalized by both 2D and 3D cell culture without triggering significant cytotoxicity and immunogenicity. Importantly, the anticancer drug doxorubicin (dox) could be loaded by passive incubation within ODNVs and dox-loaded ODNVs decreased cell viability by 90% compared to only 70% for free dox at the same concentration, indicating a higher efficiency of drug delivery by ODNVs. In addition, this high cytotoxicity effect of dox-loaded ODNVs was shown to be stable after a 2-week storage at 4 °C. Together, these findings suggested that ODNVs represent a promising candidate as drug nanocarrier for various DDS clinical applications, as demonstrated by their biocompatibility, high resistance to stress, good stability in harsh environment, and improvement of anticancer drug efficacy.

First Vesicular Self-Assembly of an Apocarotenoid Bixin in Aqueous Liquids and Its Antibacterial Activity.

Bixin 1 is the major constituent of the reddish carotenoids present in the seed-coat of Bixa orellana. The use of the extract of the seed-coat of Bixa orellana in food, cosmetics and garments is well known. The nano-sized long 24 C chain molecule has nine conjugated double bonds having extended conjugation with the '-COOH' and '-COOMe' groups present at the two ends of the molecule. Herein, we report the first self-assembly of bixin in several aqueous liquids. The molecule undergoes spontaneous self-assembly in several liquids yielding vesicular self-assembly. Characterizations of the self-assemblies of bixin were carried out by various microscopic techniques, X-ray diffraction and FTIR studies. The critical vesicular concentrations (CVCs) of the compound carried out in DMSO-water in three different solvent ratios as 2: 1 (v/v), 1: 1 (v/v) and 1: 4 (v/v) were determined to be 100 μM, 90 μM and 60 μM respectively indicating lower CVC values at higher proportion of water. Utilization of the vesicular self-assemblies of bixin have been demonstrated in the entrapment and release of fluorophores including the anticancer drugs doxorubicin and curcumin. Self-assembled bixin and curcumin loaded self-assembled bixin showed significant antibacterial activity with both Gram positive as well as Gram negative bacteria.

Surface Coating of ZIF-8 Nanoparticles with Polyacrylic Acid: A Facile Approach to Enhance Chemical Stability for Biomedical Applications.

Nanoparticles of zeolitic imidazole framework-8 (ZIF-8 NPs), which are the subclass of metal-organic frameworks consisting of Zn ion and 2-methylimidazole, have been identified as promising drug carriers since their large microporous structure is suited for encapsulating hydrophobic drug molecules. However, one of the limitations of ZIF-8 NPs is their low stability in physiological solutions, especially in the presence of water and phosphate anions. These molecules can interact with the coordinatively unsaturated Zn sites at the external surface to induce the degradation of ZIF-8 NPs. In this study, herein a facile approach is reported to enhance the chemical stability of ZIF-8 NPs by surface coating with polyacrylic acid (PAA). The PAA-coated ZIF-8 (PAA-ZIF-8) NPs are prepared by mixing ZIF-8 NPs and PAA in water. PAA coating inhibits the degradation of ZIF-8 NPs in water as well as phosphate-buffered saline over 6 days, which seems to be due to the coordination of carboxyl groups of PAA to the reactive Zn sites. Furthermore, the PAA-ZIF-8 NPs loaded with the anticancer drug doxorubicin (Dox) show cytotoxicity in human colon cancer cells. These results clearly show the feasibility of the PAA coating approach to improve the chemical stability of ZIF-8 NPs without impairing their drug delivery capability.

Self-assembled anticancer drug-loaded nanoparticles of hyaluronic acid conjugated with ursolic acid for enhanced combination chemotherapy

We propose hyaluronic acid (HA)-based nanoparticles for cancer-specific combination therapy, delivering ursolic acid (UA) and the anticancer drug doxorubicin (DOX). HA was conjugated with UA via disulfide bonds (i.e., HA-ss-UA), enabling self-assembly into nanoparticles with a hydrophobic UA core and thereby, effective encapsulation of hydrophobic DOX. The nanoparticles facilitated internalization into cancer cells due to interactions between HA and CD44 receptors. In a cancer-specific, glutathione-rich environment, the disulfide bonds in the nanoparticles were cleaved effectively, releasing more than 90 % of the conjugated UA and DOX sustainably for 2 days. In vitro testing with A549 cancer cells showed enhanced endocytosis and anticancer efficacy of the nanoparticles. Intratumoral delivery of the nanoparticles to A549-bearing mice demonstrated the most potent anticancer effect compared to other delivery formulations. Therefore, the anticancer drug-loaded nanoparticles, composed of HA conjugated with UA via disulfide bonds, represent a promising formulation for cancer-specific combination therapy.

Folic acid conjugated sodium alginate based redox responsive smart functional microgels as a potential targeted anticancer drug carrier

In this study, we have fabricated a sodium alginate-based redox-responsive, and cancer cell-targeted specific microgel using a water in oil (w/o) mini emulsion process and characterized it accordingly. Initially, we synthesized folic acid (FA)-grafted sodium alginate (SA), a biocompatible polysaccharide, followed by the preparation of a semi-interpenetrating polymer network (semi-IPN) microgel by crosslinking polyacrylamide (PAAm) with a disulfide crosslinker. The presence of disulfide linkages in the microgel formulation accelerated the release of the anti-cancer drug Doxorubicin (DOX) in the reducing domain of cancer cells (in vitro) (cumulative drug release amount 11 ± 3 %). Folic acid was incorporated into the microgels to enhance its targeting towards cancer cells due to the presence of the folate receptor on cancer cells. MTT (3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay showed an IC50 of ∼30 μg/mL of the DOX-loaded microgels towards breast cancer cells (MDA-MB-231) and a nontoxic behaviour towards normal mouse fibroblast cells (L929). FACS (Fluorescence-Activated Cell Sorting) and cell uptake studies showed significant cell apoptosis upon application of the drug-loaded microgels. In our opinion, this type of microgel can be a potential drug delivery vector for cancer treatment.

Double Encapsulation of Resveratrol and Doxorubicin in Composite Nanogel-An Opportunity to Reduce Cardio- and Neurotoxicity of Doxorubicin.

The simultaneous encapsulation of drugs into nanosized delivery systems could be beneficial for cancer therapies since it could alleviate adverse reactions as well as provide synergistic effects. However, the encapsulation of hydrophobic drugs into hydrophilic nanoparticles, such as nanogels, could be challenging. Therefore, innovative technological approaches are needed. In this research, a composite nanogel system was prepared from chitosan, albumin, and hydroxypropyl-β-cyclodextrin for co-delivery of the hydrophilic anticancer drug doxorubicin and hydrophobic antioxidant resveratrol. The nanoparticles were characterized using dynamic light scattering and found to have a hydrodynamic diameter of approx. 31 nm, narrow size distribution (PDI = 0.188), positive ƺ-potential (+51.23 mV), and pH-dependent release of the loaded drugs. FTIR and X-ray analyses proved the successful development of the composite nanogel. Moreover, the double-loaded system showed that the loading of resveratrol exerted protection against doxorubicin-induced toxicity in cardioblast H9c2 and neuroblast SH-SY5Y cells. The simultaneous loading did not influence the cytostatic effect of the antitumor agent in lymphoma L5178Y and L5178MDR cell lines.

Design and In Vitro Evaluation of Fluorescent MOF-Core CaCO₃-PEI-FA Shell Nanoparticles for Targeted Therapy of Laryngeal Cancer Cells.

Laryngeal cancer, a common malignant respiratory tumor, is primarily treated through surgery. However, challenges such as recurrence, metastasis, and drug resistance persist. In recent years, multifunctional drug delivery systems (DDS) based on nanoparticles have shown great potential in improving drug loading and release. We developed a biocompatible core-shell nanoparticle system with a zinc-based metal-organic framework (MOF) as the core, named CP1. The shell, composed of polyethyleneimine (PEI), folic acid, and calcium carbonate, forms a composite called CaCO3-PEI-FA. This system enhances biocompatibility and increases the efficacy of biomedical applications. Encapsulating CP1 within the CaCO3-PEI-FA shell allows for the targeted delivery of the anticancer drug doxorubicin (DOX) to laryngeal cancer cells (Hep-2), resulting in the CaCO3-PEI-FA@CP1@DOX system. The CaCO3-PEI-FA composite exhibits strong fluorescence with a peak around 350nm, confirming successful synthesis and demonstrating its potential as a bioimaging probe. Importantly, the nanoparticle system without DOX showed low toxicity to normal human skin fibroblasts (HSF). In vitro cytology experiments revealed a 38% inhibition rate of Hep-2 cells after 24h, highlighting the nanocomposite's significant potential in inhibiting laryngeal cancer cell proliferation and inducing apoptosis, underscoring its promise in targeted laryngeal cancer therapy.

Multifunctional nanoplatforms based on alumina-coated mesoporous silica with potential for cancer theranostics applications

Multifunctional nanoplatforms based on mesoporous silica coated with alumina were successfully and sustainably synthesized using sodium silicate extracted from rice husk ash (RHA), demonstrating the potential for cancer theranostics. The hybrid nanostructures produced (C2-600 and C4-600) from two different calcination times exhibited distinct morphologies, textural parameters, and degrees of mesoscopic organization. As expected, the Al2O3 coating on the mesoporous silica nanoparticles (MSNs) reduced the specific surface area from 720 m2/g to 122 m2/g (C2-600) and 57 m2/g (C4-600), while preserving their mesoporous structure. Additionally, both C2-600 and C4-600 showed relatively good stability across a wide pH interval, with a zeta potential of ζ = −15 mV and hydrodynamic diameter (Dh) ranging from 160 to 670 nm, depending on the pH of the medium. These peculiar characteristics resulted in high encapsulation efficiency (EE ≈ 90 %) for the doxorubicin (DOX) anticancer drug, as well as sustained drug release in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.4). Appreciably, C4-600-DOX released approximately 83 % of the drug over 96 h and demonstrated significant biodegradation in simulated biological media. Furthermore, the hybrid nanoplatforms exhibited strong optical absorption between 250 and 420 nm, along with broad and intense photoluminescence (PL) in the near-infrared (NIR) region (680–900 nm), which is highly desirable for NIR-fluorescence diagnostic imaging. Notably, the hybrid nanoplatforms without DOX were non-cytotoxic to fibroblast and Caco-2 cells, while the DOX-loaded nanoplatforms exhibited selectivity and potent anticancer activity, inhibiting approximately 80 % of Caco-2 colorectal cancer cells after 72 h. These findings demonstrate that C2-600 and C4-600 are innovative, multifunctional and biodegradable nanoplatforms with powerful potential as drug carriers and fluorescence imaging agents, making them promising candidates for cancer theranostics.

In situ growth of ZIF-8 on cellulose microspheres with high doxorubicin loading capacity and pH-sensitive for oral drug delivery

Metal-organic framework (MOF) nanoparticles are a class of porous nanomaterials with wide application prospects. Zeolitic imidazolate framework (ZIF) materials have high loading performance and pH-sensitive characteristics, which means they have great development prospects in the development of drug carrier systems. Herein, cellulose microspheres (CM) were used as a carrier for the nucleation and growth of ZIF-8 nanocrystals. CM@ZIF-8 was prepared in situ, which was more convenient, flexible, cost-effective, and highly safe. CM@ZIF-8, as a novel carrier, was used to monitor the release of the anticancer drug Doxorubicin (DOX) and prevent it from dissipating before reaching its goal. The designed DOX-loaded CM@ZIF-8 (CM@ZIF-8-DOX) system was characterized by FTIR, SEM, N2 sorption isotherm, XRD, and Cytotoxicity assay (cells survival rate 95.08 %). CM@ZIF-8-DOX exhibited controlled drug release behavior in simulated in-vitro tumor microenvironments (81.2 % drug release throughout 72h). CM@ZIF-8 simultaneously had a high loading capacity of DOX (Qe = 159.71 mg∙g−1), and the amount released under acidic conditions (pH 5.0) was greater (63.4 % after 15 h) than under neutral conditions (pH 7.4) due to the detachment of the coordination between metal ions and ligands (37.6 % after 15 h).

High loading and sustained-release system of doxorubicin-carbon dots as nanocarriers for cancer therapeutics

Nanocarriers for drugs have been investigated for decades, yet it is still challenging to achieve sustained release from nanomaterials due to drug loading inefficiency and burst release. In this study, we developed novel functional carbon dots (CDs) and investigated the therapeutic efficacy by studying the loading efficiency and release behavior of the anticancer drug doxorubicin (DOX). CDs were successfully synthesized using a one-step pyrolysis method with varying concentrations of citric acid (CA) and thiourea (TU). Functional groups, morphology, particle size, and zeta potential of synthesized CT-CDs and DOX loaded CT-CDs were investigated by UV-visible, Fluorescence, dynamic light scattering, Zeta Potential measurements, FTIR, and transmission electron microscopy. The zeta potential data revealed DOX loading onto CT-CDs by charge difference, i.e. -24.6 ± 0.44 mV (CT-CDs) and 20.57 ± 0.55 mV (DOX-CT-CDs). DOX was loaded on CDs with a loading efficiency of 88.67 ± 0.36%.In vitrodrug release studies confirmed pH-dependent biphasic drug release, with an initial burst effect and sustained release of DOX was found to be 21.42 ± 0.28% (pH 5), 13.30 ± 0.03% (pH 7.4), and 13.95 ± 0.18% (pH 9) even after 144 h at 37 °C. The CT-CDs were non-toxic and biocompatible with L929 Fibroblasts cells. The cytotoxic effect of DOX-CT-CDs showed a concentration-dependent effect after 48 h with Glioblastoma U251 cells. Flow cytometry was used to examine the cellular uptake of CT-CDs and DOX-CT-CDs in L929 and U251 cells. It was observed that the maximum CT-CDs uptake was around 75% at the end of 24 h. This study showed that the synthesized fluorescent CT-CDs demonstrated a high drug loading capacity, pH-dependent sustained release of DOX, and high cellular uptake by mammalian cells. We believe this work provides practical and biocompatible CDs for chemotherapeutic drug delivery that can be applied to other drugs for certain therapeutic aims.

A Self-Skin Permeable Doxorubicin Loaded Nanogel Composite as a Transdermal Device for Breast Cancer Therapy.

Modern drug delivery research focuses on developing biodegradable nanopolymer systems. The present study proposed a polymer-based composite nanogel as a transdermal drug delivery system for the pH-responsive targeted and controlled delivery of anticancer drug doxorubicin (DOX). Nanogels have properties of both hydrogels and nanomaterials. The β-cyclodextrin-based nanogels can enhance the loading capacity of poorly soluble drugs and promote a sustained drug release. The β-cyclodextrin-grafted methacrylic acid conjugated hyaluronic acid composite nanogel was successfully synthesized. β-Cyclodextrin was first grafted onto methacrylic acid. The composite nanogel-based drug carrier was prepared by controlled radical polymerization (CRP) of β-cyclodextrin-grafted methacrylic acid with hyaluronic acid. The doxorubicin-loaded carrier was characterized by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, zeta potential analysis, dynamic light scattering (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The drug loading and release efficiencies were carried out at different pH levels. The maximum drug loading and encapsulation efficiencies of the synthesized final nanogel composite material at pH 8.0 were 86.44 ± 2.12 and 96.07 ± 2.01%, respectively. The DOX-loaded final material showed a 90.0 ± 2.6% release percentage of DOX at pH 5.5, whereas at pH 7.4, the release percentage of DOX was observed to be only 35.0 ± 0.3%. In vitro swelling, degradation, hemocompatibility, drug release kinetics, cytotoxicity, apoptosis, cell colocalization, skin irritation, and skin permeation studies, along with in vivo pharmacokinetic studies, were performed to prove the efficacy of the synthesized nanogel composite as a transdermal carrier for doxorubicin.

Real-time electro-mechanical profiling of dynamically beating human cardiac organoids by coupling resistive skins with microelectrode arrays

Cardiac organoids differentiated from induced pluripotent stem cells are emerging as a promising platform for pre-clinical drug screening, assessing cardiotoxicity, and disease modelling. However, it is challenging to simultaneously measure mechanical contractile forces and electrophysiological signals of cardiac organoids in real-time and in-situ with the existing methods. Here, we present a biting-inspired sensory system based on a resistive skin sensor and a microelectrode array. The bite-like contact can be established with a micromanipulator to precisely position the resistive skin sensor on the top of the cardiac organoid while the 3D microneedle electrode array probes from underneath. Such reliable contact is key to achieving simultaneous electro-mechanical measurements. We demonstrate the use of our system for modelling cardiotoxicity with the anti-cancer drug doxorubicin. The electro-mechanical parameters described here elucidate the acute cardiotoxic effects induced by doxorubicin. This integrated electro-mechanical system enables a suite of new diagnostic options for assessing cardiac organoids and tissues.

PH-Responsive supramolecular vesicles for imaging-guided drug delivery: Harnessing aggregation-induced emission.

The water-soluble tribenzotriquinacene-based hexacarboxylic acid ammonium salt, TBTQ-C 6 , acts as the host component (H) forming host-guest complexes with tetraphenylethylene (TPE)-functionalized monotopic and tetratopic quaternary ammonium derivatives, G1 and G2, to yield supra-amphiphiles. These supra-amphiphiles self-assemble to form pH-responsive fluorescent vesicles, which have allowed us to capitalize on the aggregation-induced emission (AIE) effect for imaging-guided drug delivery systems. These systems exhibit efficient drug loading and pH-responsive delivery capabilities. Upon encapsulation of the anticancer drug doxorubicin (DOX), both the TPE and DOX chromophores undergo dual-fluorescence deactivation due to the energy transfer relay (ETR) effect. Under acidic conditions, the release of DOX interrupts the ETR effect, resulting in the fluorescence recovery of TPE fluorogens and DOX, allowing for real-time visual monitoring of the drug release process. Cytotoxicity experiments confirmed the low toxicity of the unloaded vectors to normal cells, while the DOX-loaded vectors were found to significantly enhance the anticancer activity of DOX against cancer cells in vitro. The AIE-featured supramolecular vesicles presented in this research hold great potential for imaging-guided drug delivery systems.

Nanocarrier-based drug delivery system with dual targeting and NIR/pH response for synergistic treatment of oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is highly heterogeneous and aggressive, but therapies based on single-targeted nanoparticles frequently address these tumors as a single illness. To achieve more efficient drug transport, it is crucial to develop nanodrug-carrying systems that simultaneously target two or more cancer biomarkers. In addition, combining chemotherapy with near-infrared (NIR) light-mediated thermotherapy allows the thermal ablation of local malignancies via photothermal therapy (PTT), and triggers drug release to improve chemosensitivity. Thus, a novel dual-targeted nano-loading system, DOX@GO-HA-HN-1 (GHHD), was created for synergistic chemotherapy and PTT by the co-modification of carboxylated graphene oxide (GO) with hyaluronic acid (HA) and HN-1 peptide and loading with the anticancer drug doxorubicin (DOX). Targeted delivery using GHHD was shown to be superior to single-targeted nanoparticle delivery. NIR radiation will encourage the absorption of GHHD by tumor cells and cause the site-specific release of DOX in conjunction with the acidic microenvironment of the tumor. In addition, chemo-photothermal combination therapy for cancer treatment was realized by causing cell apoptosis under the irradiation of 808-nm laser. In summary, the application of GHHD to chemotherapy combined with photothermal therapy for OSCC is shown to have important potential as a means of combatting the low accumulation of single chemotherapeutic agents in tumors and drug resistance generated by single therapeutic means, enhancing therapeutic efficacy.