Synergistic Therapy Research Articles

Development of Nitric Oxide-Donating Netarsudil Derivatives as a Synergistic Therapy for Glaucoma with Reduced Ocular Irritation.

Based on the synergistic therapeutic effect of nitric oxide (NO) and Rho-associated protein kinase (ROCK) inhibitors on glaucoma, a series of NO-donating Netarsudil derivatives were designed, synthesized, and their activities in vitro and in vivo were evaluated. Among them, (S)-10e released an appropriate amount of NO in aqueous humor in vitro and displayed potent ROCK inhibition. Topical administration of (S)-10e significantly lowered intraocular pressure in an acute ocular hypertension rabbit model and protected retinal ganglion cells in a magnetic microbead occlusion mouse model. A metabolism investigation revealed that (S)-10e released 7a, a metabolite after NO releasing, and 13, an active metabolite of (S)-Netarsudil, in rabbit eyes. Notably, introducing an NO donor moiety attenuated ROCK inhibition-induced ocular irritation in an sGC-independent manner, suggesting that the attenuated conjunctival hyperemia effect of (S)-10e is related to the NO-induced protein S-nitrosation of phosphodiesterase 3A (PDE3A). Overall, (S)-10e is a promising candidate for glaucoma treatment.

Polydopamine-functionalized calcium-deficient hydroxyapatite 3D-printed scaffold with sustained doxorubicin release for synergistic chemo-photothermal therapy of osteosarcoma and accelerated bone regeneration

Interior bone-tissue regeneration and rapid tumor recurrence post-resection are critical challenges in osteosarcoma and other bone cancers. Conventional bone tissue engineering scaffolds lack inhibitory effects on bone tumor recurrence. Herein, multifunctional scaffolds (named DOX/PDA@CDHA) were designed through the spontaneous polymerization of Dopamine (PDA) on the surface of Calcium Deficient Hydroxyapatite (CDHA) scaffolds, followed by in situ loading of the chemotherapeutic drug Doxorubicin (DOX). The PDA coating endowed the scaffolds with significant photothermal properties, while the gradual release of DOX provided an effective chemotherapeutic effect. The on-demand release of DOX at tumor sites, triggered by dual stimulation (near-infrared (NIR) light and the acidic pH typical of tumor microenvironments), specifically targets cancer cells, thereby mitigating systemic side effects. These unique characteristics facilitated effective osteosarcoma eradication both in vitro and in vivo. Moreover, the scaffold's composition, which mimics the mineral phase of natural bone and is enhanced by PDA's biocompatibility, promotes critical osteogenic and angiogenic processes. This facilitates not only tumor eradication but also the regeneration of healthy bone tissue. Collectively, this study presents a potent candidate for the regeneration of bone defects induced by osteosarcoma.

MnO2 nanozyme boosts synergistic photodynamic/photothermal therapy of bacterial biofilm infections

As a near-infrared (NIR) adsorbing dye approved by the FDA, indocyanine green (ICG) can serve as an attractive therapeutic agent to combat biofilm infections through synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) due to its deep-tissue penetration ability. However, ICG usually suffers from photo/thermal instability. Herein, to tackle the issues, bovine serum albumin (BSA) stabilized nanozyme MnO2 (BSA/MnO2) was synthesized by reducing manganese permanganate (KMnO4) with BSA, which was further loaded with ICG and coated with the positively charged hydroxypropyltrimethyl ammonium chloride chitosan (HACC) as the bacterial targeting moiety through noncovalent interactions. The constructed ICG@BSA/MnO2@HACC (IBMH) displays good photodynamic/thermal effects and bacterial targetability, enabling a synergistic PDT/PTT therapy against biofilm-associated infections. Compared with free ICG, IBMH exhibits enhanced photo/thermal stability owing to the O2-generating and photothermal capacities of MnO2, which significantly promotes biofilm phototherapy. Meanwhile, IBMH can effectively achieve anti-inflammatory effect due to the reactive oxygen species (ROS) scavenging capacity of nanozyme MnO2, thereby greatly accelerating wound healing after synergistic PDT/PTT. Both in vitro and in vivo assays solidly demonstrate its satisfactory anti-biofilm and anti-inflammatory effects. Therefore, our research proposes a promising and convenient strategy for developing multifunctional nanozyme for synergistic PDT/PTT of biofilm infection.

Hydrogel-based formulations for urothelial cancer therapy.

Drug infusion therapy after surgery for urothelial carcinoma is an effective measure to reduce cancer recurrence rate. Hydrogels are drug carriers with good biocompatibility and high drug loading capacity, which can optimize the pharmacokinetics of drugs in the urinary system to improve the therapeutic effect. Compared with the traditional free drug in situ perfusion, the hydrogel drug loading system can still maintain effective drug concentration in the face of continuous urinary flushing due to its good mucosal adhesion effect. The significantly prolonged drug retention time can not only improve the therapeutic effect of drugs, but also reduce the discomfort and risk of urinary tract infections caused by frequent drug infusion, and improve patient compliance. In addition, the combination of hydrogel with nanoparticles and magnetic materials can also improve the mucosal permeability and targeting effect of the hydrogel drug loading system, so as to overcome the mucus layer of urinary epithelium and the physiological barrier of tumor and minimize the impact on normal tissue and cell functions. At present, the research of hydrogels for urothelial cancer treatment involves chemotherapy, immunotherapy, gene therapy, inhibition of metabolism and multi strategy synergistic therapy. This review summarizes the research progress of hydrogels for the treatment of urothelial carcinoma, hoping to provide a reference for the future research of safe, reliable, effective, and advanced hydrogels with little side effects.

Synergistic Therapy of Melanoma by Co-Delivery of Dacarbazine and Ferroptosis-Inducing Ursolic Acid Using Biomimetic Nanoparticles.

Melanoma is one of the most aggressive types of cancer and is prone to metastasis, making current clinical treatment quite difficult. The usage of the first-line medication dacarbazine (DTIC) for melanoma is limited due to harsh side effects, limited water solubility, and a short half-life. To tackle these disadvantages, polylactic acid-hydroxyacetic acid copolymer nanoparticles (NPs) loaded with dacarbazine and ursolic acid (NPs) were fabricated, which were further encapsulated with a red blood cell membrane (RNPs). MTT, apoptosis assay, wound healing assay, colony formation assay, and immunohistochemistry were used to assess the antitumor effect of NPs and RNPs. Ferroptosis evaluation was implemented using GSH detection and the malondialdehyde assay. We found that RNPs exhibited stability and biosafety in vitro and in vivo and achieved superior anticancer ability against xenograft tumors compared with single agents and NPs, which indicated the synergistic and biomimetic efficacy. Furthermore, ferroptotic activity was observed in RNPs-treated tumor cells, and ferroptosis inhibition could partially rescue melanoma cells from RNPs-induced cell death. Collectively, this study evaluated the potential of RNPs as a novel biomimetic nanomedicine for synergistic melanoma therapy by eliciting ferroptosis in tumor cells with both anticancer activity and biosafety.

Site-Specific Location of Black Phosphorus Quantum Dot Cluster-Based Nanocomplexes for Synergistic Ion Channel Therapy and Hypoxic Microenvironment Activated Chemotherapy.

The spatiotemporal regulation of ion transport in living cell membrane channels has immense potential for providing novel therapeutic approaches for the treatment of currently intractable diseases. So far, most strategies suffer from uncontrolled ion transport and limited tumor therapy effects. On the premise of low toxicity to healthy tissues, enhancing the degree of ion overloading and the effect of tumor treatment still remains a challenging concern. Herein, an innovative strategy for synergistic ion channel therapy and hypoxic microenvironment activated chemotherapy is proposed. Biocompatible AQ4N/black phosphorus quantum dot clusters@liposomes (AQ4N/BPCs@Lip) nanocomplexes are site-specifically immobilized on the living cell membrane by a metabolic labeling strategy, eliminating the need for modifying or genetically encoding channel structures. Ascribing to the localized temperature increase of BPCs under NIR light irradiation, Ca2+ overinflux can be remotely controlled and the overloading degree was increased; moreover, the local released AQ4N can only be activated in the tumor cell, while it has no toxicity to normal cells. Compared with single intracellular Ca2+ overloading, the tumor cell viabilities decrease 2-fold with synergetic Ca2+ overloading-induced ion channel therapy and hypoxic microenvironment activated chemotherapeutics. Our study demonstrates the example of a remote-controlled ion influx and drug delivery system for tumor therapy.

Dialdehyde cellulose nanofibrils/polyquaternium stabilized ultra-fine silver nanoparticles for synergistic antibacterial therapy

Dialdehyde cellulose nanofibrils (DACNF) and Polyquaternium-10 (PQ: chloro-2-hydroxy-3-(trimethylamino) propyl polyethylene glycol cellulose) have become increasingly favored as antibacterial substances due to their advantageous characteristics. DACNF exhibits exceptional mechanical properties and biocompatibility, whereas PQ demonstrates a positive charge that enhances its antibacterial activity. Combined in a DACNF/PQ mixture, they provide an excellent template material for preparing and stabilizing ultra-fine (~ 10.3 nm) silver nanoparticles (AgNPs) at room temperature. Here, the dialdehyde group of DACNF functions as a reducing agent, while the quaternary ammonium of PQ and carboxylate groups of DACNF synergistically helped in-situ generation of AgNPs uniformly. The synthesized nanocomposites, namely PQ@AgNPs, AgNPs@DACNF, and AgNPs@DACNF/PQ, were subjected to comprehensive characterization using various advanced analytical techniques. The films containing AgNPs@DACNF and AgNPs@DACNF/PQ, fabricated via vacuum filtration, exhibited excellent mechanical properties of 9.78 ± 0.21 MPa, and demonstrated superior antibacterial activity against both Escherichia coli and Staphylococcus aureus. Additionally, the silver ion leaching from the prepared composite films was well controlled. The fabricated nanocomposites also effectively inhibited bacterial biofilm formation. It was also found to be highly biocompatible and non-toxic to human skin fibroblast cells. Furthermore, the nanocomposites exhibited enhanced migration of human dermal fibroblasts, suggesting their potential in facilitating wound healing processes.

As Aggregation‐Induced Emission Meets with Noncovalent Conformational Locks: Subtly Regulating NIR‐II Molecules for Multimodal Imaging‐Navigated Synergistic Therapies

Phototheranostics is growing into a sparking frontier in disease treatment. Developing single molecular species synchronously featured by powerful absorption capacity, superior second near‐infrared (NIR‐II) fluorescence and prominent photothermal conversion ability is highly desirable for phototheranostics, yet remains formidably challenging. In this work, we propose a molecular design philosophy that the integration of noncovalent conformational locks (NoCLs) with aggregation‐induced emission (AIE) in a single formulation is able to boost multiple photophysical properties for efficient phototheranostics. The introduction of NoCLs skeleton with conformation‐locking feature in the center of molecular architecture indeed elevates the structural planarity and rigidity, which simultaneously promotes the absorption capacity and bathochromic‐shifts the emission wavelength centered in NIR‐II region. Meanwhile, the AIE tendency mainly originated from flexibly propeller‐like geometry at the ends of molecular architecture eventually endows the molecule with satisfactory emission intensity and photothermal conversion in aggregates. Consequently, by utilizing the optimized molecule, unprecedented performance on NIR‐II fluorescence‐photoacoustic‐photothermal trimodal imaging‐guided photothermal‐chemo synergistic therapy is demonstrated by the precise tumor diagnosis and complete tumor ablation.

Fluorinated triphenylamine phthalocyanine @ silica-coated gold nanorods: A photoactivated lysosome escape and targeting mitochondria two-photon probe for imaging-guided photothermal synergistic photodynamic therapy in cancer cells

The timely evasion of nanomedicines from lysosomes is essential to avert premature degradation under the acidic and hydrolytic conditions characteristic of these cellular compartments. However, the development of effective strategies has been hindered by the complexity of design material and the scarcity of practical methods. In this study, we have synthesized a novel nanoparticle, designated as TPA-BPAF-SiPc@AuNR@SiO2. This nanoparticle was prepared by encapsulating near-infrared fluorinated triphenylamine-substituted silicon phthalocyanines (TPA-BPAF-SiPc) within mesoporous silica-coated gold nanorods (AuNR@SiO2). TPA-BPAF-SiPc@AuNR@SiO2 functions as a dual-function two-photon probe, facilitating photoactivated lysosome escape and targeting mitochondria. The inherent aggregation-induced emission (AIE) two-photon fluorescence of TPA-BPAF-SiPc is notably bright when encapsulated in AuNR@SiO2 nanocarriers, a phenomenon not observed in polymer nanocarriers composed of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) or in THF/water mixtures. Upon irradiation, this nanoparticle autonomously escapes from lysosomes and selectively targets mitochondria, a process can be visually monitored in real-time through the two-photon AIE fluorescence of TPA-BPAF-SiPc. Moreover, upon activation, TPA-BPAF-SiPc@AuNR@SiO2 produces a substantial quantity of reactive oxygen species (ROS) and induces hyperthermia effects, showcasing its potential for effective photodynamic therapy (PDT) in conjunction with synergistic hyperthermia. Flow cytometry data corroborate the induction of tumor cell death through both necrosis and apoptosis pathways by TPA-BPAF-SiPc@AuNR@SiO2. This study underscores the potential of TPA-BPAF-SiPc@AuNR@SiO2 as a multifunctional probe capable of enabling lysosome escape, mitochondria targeting, and two-photon fluorescence imaging-guided photothermal synergistic photodynamic therapy, specifically tailored for the treatment of breast cancer.

As Aggregation-Induced Emission Meets with Noncovalent Conformational Locks: Subtly Regulating NIR-II Molecules for Multimodal Imaging-Navigated Synergistic Therapies.

Phototheranostics is growing into a sparking frontier in disease treatment. Developing single molecular species synchronously featured by powerful absorption capacity, superior second near-infrared (NIR-II) fluorescence and prominent photothermal conversion ability is highly desirable for phototheranostics, yet remains formidably challenging. In this work, we propose a molecular design philosophy that the integration of noncovalent conformational locks (NoCLs) with aggregation-induced emission (AIE) in a single formulation is able to boost multiple photophysical properties for efficient phototheranostics. The introduction of NoCLs skeleton with conformation-locking feature in the center of molecular architecture indeed elevates the structural planarity and rigidity, which simultaneously promotes the absorption capacity and bathochromic-shifts the emission wavelength centered in NIR-II region. Meanwhile, the AIE tendency mainly originated from flexibly propeller-like geometry at the ends of molecular architecture eventually endows the molecule with satisfactory emission intensity and photothermal conversion in aggregates. Consequently, by utilizing the optimized molecule, unprecedented performance on NIR-II fluorescence-photoacoustic-photothermal trimodal imaging-guided photothermal-chemo synergistic therapy is demonstrated by the precise tumor diagnosis and complete tumor ablation.

Tumor Microenvironment-Responsive Biodegradable Nanomedicine for Self-Enhanced Synergistic Chemo-, Photothermal, and Chemodynamic Therapy.

The nanoscale multidrug codelivery system for synergistic therapy is an effective strategy for tumor treatment. However, the low drug delivery efficiency and poor therapeutic effects limit its application. Here, based on the coordination effect of Artemisinin (Art), quercetin (Qc), and Fe3+, we had constructed a safe and efficient carrier-free hyaluronic acid (HA)-modified Art-Fe-Qc nanoparticles (AFQ@HA NPs) for enhanced chemotherapy/photothermal therapy (PTT)-chemodynamic therapy (CDT) synergistic therapy, which achieved an ultrahigh drug loading efficiency and a multifunction anticancer strategy. The results showed that high drug loading was achieved based on drug coordination self-assembly, with Art and Qc contents of 38.6 and 42.7%, respectively. At the same time, based on the Qc-Fe coordination molecular network, the system had excellent photothermal conversion performance with an efficiency of 57.3% and could effectively inhibit the expression of HSP70, achieving enhanced PTT. Further, under the stimulation of excessive H2O2 and glutathione (GSH) in the tumor microenvironment, the AFQ@HA NPs were continuously degraded, while releasing Art and Fe3+/Fe2+ to achieve iron ion-enhanced CDT. The results of in vitro and in vivo experiments showed that AFQ@HA NPs could achieve chemotherapy-PTT-CDT synergistic therapy in response to tumor microenvironment by passively targeting and actively targeting tumor cells with CD44, demonstrating its excellent targeted antitumor effects.

Cu2O-SnO2-PDA heterozygous nanozyme doped hydrogel mediated conglutinant microenvironment regulation for wound healing therapy

Bacterial infection significantly hinders the wound healing process. Overuse of antibiotics has led to the rise of drug resistance in bacteria, making the development of smart medical dressings that promote wound healing without antibiotics, a critical need. In this study, Cu₂O-SnO₂-PDA (PCS) nanoenzymes with Fenton-like activity and high photothermal conversion efficiency were developed. These nanoenzymes were then incorporated into a hydrogel through cross-linking of acrylamide (AM) and N-[Tris-(hydroxymethyl)methyl] acrylamide (THMA), forming a tough, highly-adhesive, and self-healing composite hydrogel (AT/PCS) with antimicrobial properties. The AT/PCS hydrogel exhibits excellent mechanical strength and adhesion, facilitating increased oxygen levels and strong adherence to the wound site. Moreover, it effectively regulates the wound microenvironment by combining synergistic chemodynamic therapy (CDT) and photothermal therapy (PTT) for antibacterial treatment. The AT/PCS hydrogel enhances collagen deposition and expedites wound healing in a rat model, largely due to its potent antibacterial properties.

Near-Infrared-II Photoactivated Iron(III) Complexes for Highly Efficient RNS and ROS Synergistic Therapy.

Reactive nitrogen species (RNS) are more lethal than reactive oxygen species (ROS), which gives them a very promising future in the field of cancer treatment. However, there are still a few drugs available for RNS generation. In this work, two 5th-order nonlinear optical materials, FB-Fe(III)/SNP@PEG and FB-Fe(II)-FB/SNP@PEG, are synthesized. The outstanding nonlinear optical properties of FB-Fe(III)/SNP@PEG help to achieve generation of bounteous superoxide anions (O2•-) in deep tissues, while sodium nitroprusside (SNP) provides NO in the body, both of which are prerequisites for RNS generation. Meanwhile, type I and type II ROS were also generated under irradiation of a 1600 nm laser. Based on the synergistic effect of ROS and RNS, FB-Fe(III)/SNP@PEG induced mitochondrial damage and DNA fragmentation and inhibited tumor cells through apoptosis, possessing better therapeutic effects than FB-Fe(II)-FB/SNP@PEG. This work put forward an innovative strategy to achieve the cooperative release of RNS and ROS in deep tissues, which provides insights and ideas for applying nonlinear optical materials to RNS therapy.

A nanotheranostics with hypoxia-switchable fluorescence and photothermal effect for hypoxia imaging-guided immunosuppressive tumor microenvironment modulation

Modulating the immunosuppressive tumor immune microenvironment (TIME) is considered a promising strategy for cancer treatment. However, effectively modulating the immunosuppressive TIME within hypoxic zones remains a significant challenge. In this work, we developed a hypoxia-responsive amphiphilic drug carrier using boron-dipyrromethene (BODIPY) dye-modified chitosan (CsB), and then fabricated a hypoxia-targeted nanotheranostic system, named CsBPNs, through self-assembly of CsB and pexidartinib (5-((5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl), PLX3397), an immunotherapeutic drug targeting tumor-associated macrophages (TAMs), for synergistic photothermal/immunotherapy and hypoxia imaging. CsBPNs demonstrated uniform size, good stability, and hypoxia-switchable fluorescence and photothermal effects, enabling deep penetration and hypoxia imaging capacities in three-dimensional tumor cell spheres and tumor tissues. In vitro and in vivo experiments showed that CsBPNs under laser irradiation promoted TAMs repolarization, reversed the immunosuppressive TIME, and enhanced the therapeutic outcome of PLX3397 in solid tumors by facilitating deep delivery into hypoxic regions and synergistic photothermal therapy. This work provides a new strategy for detecting and modulating the immunosuppressive TIME in hypoxic zones, potentially enabling more precise and effective photo-immunotherapy in the future.

A “precision medicine” nanoplatform for synergistic photothermal therapy and chemotherapy in hepatocellular carcinoma

Targeted peptide-mediated photothermal therapy (PTT) in combination with chemotherapy has great potency in the field of “precision medicine” because of its ability to increase drug enrichment in the focal region, reduce systemic toxicity, and provide the advantages of superb spatial-temporal control and non-invasiveness. In this work, we developed a FoxM1c-targeted nanoplatform (GSDP) for synergistic PTT and chemotherapy for hepatocellular carcinoma (HCC). Under irradiation with an 808-nm laser, the enriched nanodrug in tumor sites could convert near-infrared (NIR) light into heat, causing tumor temperature to exceed the safety threshold, the high temperature triggers the release of Doxorubicin (DOX) correspondingly, which can achiev the synergistic PTT-chemotherapy treatment. More strikingly, the nanoplatform achieved "precision medicine" of tumors due to the modification of 9R-P201 peptide, ultimately achieved a tumor suppression rate of 84.6% in HCC. Hence, the design of this synergistic therapeutic platform offers a new perspective for improving the therapeutic efficacy of HCC.

Photothermal and enhanced chemodynamic reinforced anti-tumor therapy based on PDA@POM nanocomposites

Chemodynamic therapy (CDT) and photothermal therapy (PTT) have both demonstrated considerable efficacy in the tumor treatment individually, owing to their non-invasive nature and excellent selectivity. However, due to the propensity of tumors for metastasis and recurrence, a singular therapeutic approach falls short of achieving optimal treatment outcomes. Polydopamine (PDA) has excellent photothermal conversion ability and polyoxometalates (POMs) possess diverse enzymatic activities. Here, we synthesized PDA@POM nanospheres comprising polydopamine-coated Tungsten-based polyoxometalate (W-POM). These nanospheres leverage dual enzymatic activities that synergistically enhance both chemodynamic and photothermal therapies for tumor treatment. The PDA-mediated PTT effect enables precise tumor cell destruction, while the W-POM nanozymes catalyzes the generation of highly toxic reactive oxygen species (ROS) from hydrogen peroxide within tumor cells through a Fenton-like reaction, which mitigates tumor hypoxia and induces tumor cell death. This synergistic photothermal catalytic therapy shows enhanced efficacy in tumor suppression, providing a promising new approach for tumor treatment.

Development of a sequential release nanomaterial for co-delivery of hypoxia-induced tirapazamine and HIF-1α siRNA in cancer therapy

Unlike traditional drug carriers, sequential drug delivery systems can release different drugs in order, with the first released drug providing a prerequisite for the later released drug to maximize its function, thereby achieving stronger anti-tumor effects. Herein we constructed a temporal sequential system designated TPZ@MSN/HIF-1α siRNA@PDA@GOx (MTRPG) in which mesoporous silica nanoparticles were used as cores to load hypoxia induced chemotherapy drug tirapazamine (TPZ) and gene targeted nucleic acid drug HIF-1α siRNA, polydopamine (PDA) as acid –responsive coating as well as to realize photothermal therapy, and glucose oxidase (GOx) as the outermost layer to achieve starvation therapy and construct a deepened hypoxia to activate TPZ. Through in vitro and in vivo experiments, we demonstrated that the first released glucose oxidase catalyzed the oxidation of glucose, achieving starvation treatment while reducing the acidic environment and further exacerbating hypoxia in tumor cells. The reduced acidic conditions enabled the degradation of PDA, resulting in the release of loaded HIF-1α siRNA and TPZ. At the same time, PDA could also exert photothermal therapy under 808 nm near-infrared (808 nm NIR) laser irradiation. The later released hypoxia induced chemotherapy drug TPZ amplifies its anti-tumor activity under intensified hypoxia conditions. Meanwhile, the released HIF-1α siRNA interfered with the up-regulated HIF-1α induced by the deepened hypoxia condition, which caused hypoxia tolerance in tumors, reduced its expression activity, and achieved synergistic killing of tumor cells with chemotherapy. This work provides an effective multimodal synergistic therapy strategy to promote tumor therapeutic index, which may possess a promising future in clinical application.

Highly Efficient Synergistic Chemotherapy and Magnetic Resonance Imaging for Targeted Ovarian Cancer Therapy Using Hyaluronic Acid-Coated Coordination Polymer Nanoparticles.

The diagnosis and treatment of ovarian cancer (OC) are still a grand challenge, more than 70% of patients are diagnosed at an advanced stage with a dismal prognosis. Magnetic resonance imaging (MRI) has shown superior results to other examinations in preoperative assessment, while cisplatin-based chemotherapy is the first-line treatment for OC. However, few previous studies have brought together the two rapidly expanding fields. Here a technique is presented using cisplatin prodrug (Pt-COOH), Fe3+, and natural polyphenols (Gossypol) to construct the nanoparticles (HA@PFG NPs) that have a stable structure, controllable drug release behavior, and high drug loading capacity. The acidic pH values in tumor sites facilitate the release of Fe3+, Pt-COOH, and Gossypol from HA@PFG NPs. Pt-COOH with GSH consumption and cisplatin-basedchemotherapy plus Gossypol with pro-apoptotic effects displays asynergisticeffect forkillingtumorcells. Furthermore, the release of Fe3+ at the tumor sites promotes ferroptosis and enables MRI imaging of OC. Inthe patient-derived tumor xenograft (PDX)model, HA@PFG NPs alleviate the tumor activity. RNA sequencing analysis reveals that HA@PFG NPs ameliorate OC symptoms mainly through IL-6 signal pathways. This work combines MRI imaging with cisplatin-based chemotherapy, which holds great promise for OC diagnosis and synergistic therapy.

Calcium ion rapid release and dual-mode synergistic regulation influx for enhanced therapeutic efficacy

Calcium ion-intervention therapy, predicated on the principle of intracellular Ca2+ overload, has emerged as a promising non-invasive strategy for oncological treatment. However, the precise delivery of Ca2+ to the tumor site and the effective modulation of Ca2+ influx is critical for enhancing the therapeutic effect of ionic interventions. Herein, we report the development of a novel endogenous hydrogen sulfide (H2S)-responsive nanoplatform, denoted as Ca2+@HKUST-1@PVP, which enables H2S-rapid responsive, targeted Ca2+ delivery, rapid ion release, and the synergistic modulation of calcium ion channels through photothermal and reactive oxygen species (ROS) mechanisms. The integration of HKUST-1 within the nanoplatform allows for selective reaction with tumor-associated H2S, triggering the rapid release of Ca2+ (around 80 % within two hours) and the concurrent generation of cooper sulfide (CuS) with near infrared (NIR) absorbance properties. These CuS serve a dual role as highly efficient photothermal agents and Fenton-like catalysts, which act in concert to modulate Ca2+ channels. The orchestrated cascade of events—encompassing rapid ion release, controllable photothermal effect and ROS-mediated modulation of Ca2+ influx—subverts the tumor’s calcium homeostasis and significantly amplifies the cytotoxic effects of calcium overload. Both in vitro and in vivo studies demonstrate that Ca2+@HKUST-1@PVP induces remarkable cytotoxicity and therapeutic efficacy through photothermal and ROS-enhanced calcium overload, surpassing the performance of HKUST-1 without Ca2+ loading. This study, therefore, presents a colon cancer-specific nanoplatform for photothermal and ROS synergistic ion-interference therapy, offering a novel avenue for the treatment of malignancies.

Engineering optimal gold nanorod-loaded hollow mesoporous organosilica nanotheranostics for NIR-II photoacoustic microscopy imaging and tumor synergistic therapy

Biodegradable hollow mesoporous organosilica nanoparticles (HMON)-based nanotheranostics has recently gained growing interests due to their tremendous potential as an attractive platform for cancer imaging and therapy. However, the engineering of HMON-based nanotheranostics for size-dependent biological profile on in vivo tumor uptake, biodistribution and retention in tumor region have not been achieved to date. Here, a novel tumor microenvironment (TME)-activated nanoplatform employing miniature gold nanorod-loaded HMON (Au@HMON) with tunable hollow cavity of HMON coating is presented, and its application in the second near infrared (NIR-II, 1000–1700 nm) window photoacoustic microscopy (PAM) imaging-guided synergistic chemo-photothermal therapy is studied by loading doxorubicin (DOX). The cancer cell membrane (CCM) biomimetic nanotheranostics (Au@HMON-DOX@CCM) exhibited a high photothermal conversion efficiency of 41.1 % for photothermal therapy (PTT) and PAM imaging. Among the three investigated nanotheranostics, the 221 nm-nanotheranostics exhibited stronger PAM signal and higher drug loading efficacy than the small counterparts (156- and 186-nm) due to the thicker HMON coating layer, larger surface area and intermediate void structure. Therefore, synergistic chemo-photothermal therapy using 221 nm-nanotheranostics is achieved to efficiently inhibit tumor growth. This strategy affords design parameters for engineering HMON-based “all-in-one” nanotheranostics for photoacoustic imaging-guided cancer treatment.