Tumor-targeted delivery of hyaluronic acid/polydopamine-coated Fe2+-doped nano-scaled metal-organic frameworks with doxorubicin payload for glutathione depletion-amplified chemodynamic-chemo cancer therapy.

Chemodynamic therapy (CDT), an emerging cancer treatment modality, uses multivalent metal elements to convert endogenous hydrogen peroxide (H2O2) to toxic hydroxyl radicals (•OH) via a Fenton or Fenton-like reaction, thus eliciting oxidative damage of cancer cells. However, the antitumor potency of CDT is largely limited by the high glutathione (GSH) concentration and low catalytic efficiency in the tumor sites. The combination of CDT with chemotherapy provides a promising strategy to overcome these limitations. In this work, to enhance antitumor potency by tumor-targeted and GSH depletion-amplified chemodynamic-chemo therapy, the hyaluronic acid (HA)/polydopamine (PDA)-decorated Fe2+-doped ZIF-8 nano-scaled metal-organic frameworks (FZ NMs) were fabricated and utilized to load doxorubicin (DOX), a chemotherapy drug, via hydrophobic, π-π stacking and charge interactions. The attained HA/PDA-covered DOX-carrying FZ NMs (HPDFZ NMs) promoted DOX and Fe2+ release in weakly acidic and GSH-rich milieu and exhibited acidity-activated •OH generation. Through efficient CD44-mediated endocytosis, the HPDFZ NMs internalized by CT26 cells not only prominently enhanced •OH accumulation by consuming GSH via PDA-mediated Michael addition combined with Fe2+/Fe3+ redox couple to cause mitochondria damage and lipid peroxidation, but also achieved intracellular DOX release, thus eliciting apoptosis and ferroptosis. Importantly, the HPDFZ NMs potently inhibited CT26 tumor growth in vivo at a low DOX dose and had good biosafety, thereby showing promising potential in tumor-specific treatment.

Pt/Pd dual-modified porphyrin metal-organic frameworks for NIR-II photothermal-enhanced photodynamic/catalytic therapy.

Photodynamic therapy (PDT) and catalytic therapy were promising treatment modes, but tumor hypoxia and poor catalytic activity severely limited their efficacies. Herein, using a porphyrin metal-organic framework (PCN-224) as nanocarrier, a platinum/palladium (Pt/Pd) dual-modified PCN-224 nanoprobe (PCN-224-Pt@Pd) with strong peroxidase (POD)/catalase (CAT)-like activities was developed, achieving photothermal-promoted PDT/catalytic therapy. Compared with single ultrasmall Pt modifying, CAT-like activity of Pt/Pd dual-modifying increased oxygen concentration from 6.24 to 9.35 mg/L, which improved singlet oxygen (1O2) yield from 63.8 % to 82.9 %. Moreover, POD-like activity of Pt/Pd dual-modifying significantly accelerated hydroxyl radicals (·OH) generation. Importantly, PCN-224-Pt@Pd possessed near-infrared II (NIR-II) photothermal effect with a high efficiency (55.6 %), which further promoted ·OH production. Under combined therapy of PCN-224-Pt@Pd, the cell survival rate greatly reduced to 5.8 %, and the tumors were cured, suggesting NIR-II photothermal-enhanced PDT/catalytic therapy.

X-ray triggered scintillator versatile nanocatalytic platform for synergistic photodynamic/chemodynamic therapy.

Nanocatalysts with photodynamic therapy (PDT) and chemodynamic therapy (CDT) are excellent for tumor therapy. However, it is still challenging to achieve complete tumor eradication due to the drawbacks of limited penetration depth of intratumoural tissues, hypoxia and complexity of the tumor microenvironment (TME). Herein, we fabricated an integrated multifunctional nanoreactor (LuAG:Tb/Ce-RB@ZIF-8-Au2Pt-HA, LRZAPH) combining scintillating nanoparticles (SCNPs, LuAG:Tb/Ce), a metal-organic framework (ZIF-8), and bimetallic Au2Pt for X-ray-triggered PDT and dual noble-metal nanozyme catalyzed CDT. Such a nanoreactor not only significantly enhanced the PDT effect under X-ray irradiation through full resonance energy transfer from LuAG:Tb/Ce scintillator to Ross Bengal (RB), but also facilitated the reactive oxygen species (ROS) and oxygen (O2) production through the excellent peroxidase-like (POD-like) and catalase-like (CAT-like) catalytic properties of Au2Pt nanozymes. O2 also alleviates hypoxia in intratumoural tissues during coordinated PDT. In addition, the dissociation behavior of ZIF-8 with pH-responsive and targeted of hyaluronic acid (HA) in acidic TME significantly enhanced the therapeutic efficacy of LRZAPH nanocatalysts. Significantly, the high tumor growth inhibition rate of 93 % was revealed due to radiotherapy (RT)/PDT/CDT synergetic therapy in vivo, which minimized the toxic and side effects of conventional clinical radiotherapy/chemotherapy on human. The synergistic effect of LRZAPH nanocatalysts on PDT and catalytically induced CDT is expected to provide new pathways for effective treatment of deep tumors.

Modified Ce/Zr-MOF Nanoparticles Loaded with Curcumin for Alzheimer's Disease via Multifunctional Modulation.

Introduction: Alzheimer's disease (AD), a neurodegenerative condition, stands as the most prevalent form of dementia. Its complex pathological mechanisms and the formidable blood-brain barrier (BBB) pose significant challenges to current treatment approaches. Oxidative stress is recognized as a central factor in AD, underscoring the importance of antioxidative strategies in its treatment. In this study, we developed a novel brain-targeted nanoparticle, Ce/Zr-MOF@Cur-Lf, for AD therapy. Methods: Layer-by-layer self-assembly technology was used to prepare Ce/Zr-MOF@Cur-Lf. In addition, the effect on the intracellular reactive oxygen species level, the uptake effect by PC12 and bEnd.3 cells and the in vitro BBB permeation effect were investigated. Finally, the mouse AD model was established by intrahippocampal injection of Aß1-42, and the in vivo biodistribution, AD therapeutic effect and biosafety of the nanoparticles were researched at the animal level. Results: As anticipated, Ce/Zr-MOF@Cur-Lf demonstrated efficient BBB penetration and uptake by PC12 cells, leading to attenuation of H2O2-induced oxidative damage. Moreover, intravenous administration of Ce/Zr-MOF@Cur-Lf resulted in rapid brain access and improvement of various pathological features of AD, including neuronal damage, amyloid-ß deposition, dysregulated central cholinergic system, oxidative stress, and neuroinflammation. Conclusion: Overall, Ce/Zr-MOF@Cur-Lf represents a promising approach for precise brain targeting and multi-target mechanisms in AD therapy, potentially serving as a viable option for future clinical treatment.

Therapeutic effects of DOX-loaded hydrogel MOF nanocarriers on triple negative breast cancer and derivative design via reinforcement learning.

Triple negative breast cancer (TNBC) is one of the most difficult of all types of breast cancer to treat. TNBC is characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The development of effective drugs can help to alleviate the suffering of patients. The novel nickel(II)-based coordination polymer (CP), [Ni2(HL)(O)(H2O)3·H2O] (1) (where H4L=[1,1':2',1''-triphenyl]-3,3'',4',5'-tetracarboxylic acid), was synthesized via solvothermal reaction in this study. The overall structure of CP1 was fully identified by SXRD, Fourier transform infrared spectroscopy and elemental analysis. Using advanced chemical synthesis, we developed Hyaluronic Acid/Carboxymethyl Chitosan-CP1@Doxorubicin (HA/CMCS-CP1@DOX), a nanocarrier system encapsulating doxorubicin (DOX), which was thoroughly characterized using Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and Thermogravimetric Analysis (TGA). These analyses confirmed the integration of doxorubicin and provided data on the nanocarriers' stability and structure. In vitro experiments showed that this system significantly downregulated Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) in triple-negative breast cancer cells and inhibited their proliferation. Molecular docking simulations revealed the biological effects of CP1 are derived from its carboxyl groups. Using reinforcement learning, multiple new derivatives were generated from this compound, displaying excellent biological activities. These findings highlight the potential clinical applications and the innovative capacity of this nanocarrier system in drug development.

Co-Delivery of VEGF siRNA and THPP via Metal-Organic Framework Reverses Cisplatin-Resistant Non-Small Cell Lung Cancer and Inhibits Metastasis through a MUC4 Regulating Mechanism.

Cisplatin resistance significantly impacts the antitumor efficacy of cisplatin chemotherapy and contributes to poor prognosis, including metastasis. In this study, we present the utilization of metal-organic framework (MOF) nanoparticles as the therapeutic component and drug loading scaffold for implementing a ternary combination therapeutic strategy to combat cisplatin-resistant lung cancer and metastasis. Specifically, by engineering MOFs (Cis@MOF-siVEGF) through the self-assembly of THPP as photosensitizer for photodynamic therapy (PDT), along with the incorporation of cisplatin (DDP) and VEGF siRNA (siVEGF), we propose the leverage of photodynamic-induced oxidative damage and gene silencing of the angiogenic factor to reverse cisplatin resistance and sensitize therapeutic potency. Our findings demonstrated that the chemo/photodynamic/antiangiogenic triple combination therapy via Cis@MOF-siVEGF under irradiation effectively inhibits cisplatin-resistant tumor growth and induces abscopal effects. Importantly, molecular mechanistic exploration suggested that MUC4 exerted regulatory effects on governing cancer metastasis, thus representing a potential immunotherapeutic target for cancer intervention. Overall, our study creates a MOFs-based multicomponent delivery platform for complementary therapeutic modules with synergistically enhanced antitumor efficacy and sheds light on potential regulatory mechanisms on cisplatin-resistance cancers.

A Tumor-Homing Nanoframework for Synergistic Microwave Tumor Ablation and Provoking Strong Anticancer Immunity Against Metastasis.

Microwave thermotherapy (MT) is a clinical local tumor ablation modality, but its applications are limited by its therapeutic efficacy and safety. Therefore, developing sensitizers to optimize the outcomes of MT is in demand in clinical practice. Herein, we engineered a special nanoframework (i.e., FdMI) based on a fucoidan-decorated zirconium metal-organic framework incorporating manganese ions and liquid physisorption for microwave tumor ablation. The monodisperse nanoframework exhibited both microwave thermal effects and microwave dynamic effects, which could effectively kill cancer cells by efficient intracellular drug delivery. Through fucoidan-mediated targeting of P-selectin in the tumor microenvironment (TME), the FdMI effectively accumulated in tumor regions, leading to significant eradication of orthotropic triple-negative breast cancer (TNBC) and aggressive Hepa1-6 liver tumors by the synergistic effects of microwave thermotherapy/dynamic therapy (MT/MDT). The eradication of primary tumors could activate systemic immune responses, which effectively inhibited distant TNBC tumors and lung metastasis of Hepa1-6 liver tumors, respectively. This work not only engineered nanoparticle sensitizers for tumor-targeted synergistic MT/MDT but also demonstrated that nanocarrier-based microwave tumor ablation could stimulate antitumor immunity to effectively inhibit distant and metastatic tumors, demonstrating the high potential for effectively managing advanced malignant tumors.

Metal-Organic Nanomaterials for Tumor Metabolic Blockade and Image to Increase Tumor Therapy.

The abnormal energy metabolism level of a tumor reduces the efficiency of chemotherapy. Metal-organic nanomaterials (MONs) with high drug loading efficiency, easy processes of synthesis, and controlled drug release have shown great potential in metabolic blocking and enhancement of tumor therapy. These metal-organic nanomedicines have been reported to modulate glycolysis or oxidative phosphorylation to provide monotherapy or combined therapies in tumorous treatments. In addition, the encapsulation or coordination of fluorescent dyes into MONs endowed them with the imaging ability of tumor metabolism. Herein, this Perspective summarizes the progress of MONs as therapeutic agents or imaging probes for application during tumor metabolic blocking or imaging, providing solid inspiration for biomedical applications of effective biomaterials. In addition, the current drawbacks of MONs for further biological applications in the future were discussed, giving stimulation of innovation and development in biomedical applications of MONs.

Metal-organic frameworks: potential synergies with cold atmospheric plasmas for cancer control.

Metal-organic frameworks (MOFs) have attracted increasing attention for cancer treatment due to their unique characteristics such as crystallized porous structures, high surface area, and diverse and modifiable chemical properties. Despite the plethora of reports on MOF-based onco-therapeutic designs, these nanocomposites have rarely been launched for clinical use, given, at least, one unavoidable concern, i.e., biosafety. Among the diverse possibilities that MOFs can be engaged for cancer treatment, one unignorable opportunity is how MOFs can be combined with other emerging anti-cancer approaches as one treatment modality to resolve issues of either one for surpassed treatment efficacy. Taking cold atmospheric plasmas (CAPs) as an example, this review delineates the unique features of MOFs and discusses the possible synergies they can create with CAPs for mutual benefits. By providing one example on how MOFs can help overcome the issues of other pre-clinical cancer treatment regimens, this review identifies one research niche that may thrive the field of plasma medicine and revolutionize the schema of MOFs for biological applications.

Fe-HCOF-PEG2000 as a Hypoxia-Tolerant Photosensitizer to Trigger Ferroptosis and Enhance ROS-Based Cancer Therapy.

Background: The hypoxic tumor microenvironment and single mechanisms severely limit the photodynamic therapy (PDT) efficiency of covalent organic framework (COF) nanoparticles in cancer treatment. Purpose: Here, we propose an iron-loaded, hydrophilic 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000)-modified hollow covalent organic framework (HCOF), Fe-HCOF-PEG2000, for use in hypoxic PDT and ferroptosis therapy owing to its type I and II photodynamic ability and iron nanoparticle loading property. Results: Fe-HCOF-PEG2000 nanoparticles (Fe-HCOFs-PEG2000) with semiconducting polymers and microporous skeletons allow efficient photophysical properties. Moreover, the iron nanoparticles on Fe-HCOF-PEG2000 caused ferroptosis and further enhanced tumor elimination under normoxic and hypoxic conditions. DSPE-PEG2000 endowed Fe-HCOF-PEG2000 with hydrophilicity, allowing it to circulate and accumulate in organs rich in blood supply, especially tumors. 808 nm NIR activated Fe-HCOF-PEG2000 aggregated in tumors and significantly inhibited tumor growth under hypoxia. Conclusion: To our knowledge, Fe-HCOF-PEG2000 is the leading combination of type I/II PDT and ferroptosis. The strong antitumor effects of this nanomaterial suggest prospects for clinical translation as a tumor nanotherapy drug.

Metal-organic-framework-based sitagliptin-release platform for multieffective radiation-induced intestinal injury targeting therapy and intestinal flora protective capabilities.

In patients with abdominal or pelvic tumors, radiotherapy can result in radiation-induced intestinal injury (RIII), a potentially severe complication for which there are few effective therapeutic options. Sitagliptin (SI) is an oral hypoglycemic drug that exhibits antiapoptotic, antioxidant, and anti-inflammatory activity, but how it influences RIII-associated outcomes has yet to be established. In this study, a pH-responsive metal-organic framework-based nanoparticle platform was developed for the delivery of SI (SI@ZIF-8@MS NP). These NPs incorporated mPEG-b-PLLA (MS) as an agent capable of resisting the effects of gastric acid, and are capable of releasing Zn2+ ions. MS was able to effectively shield these SI@ZIF-8 NPs from rapid degradation when exposed to an acidic environment, enabling the subsequent release of SI and Zn2+ within the intestinal fluid. Notably, SI@ZIF-8@MS treatment was able to mitigate radiation-induced intestinal dysbiosis in these mice. restored radiation-induced changes in bacterial composition. In summary, these data demonstrate the ability of SI@ZIF-8@MS to protect against WAI-induced intestinal damage in mice, suggesting that these NPs represent a multimodal targeted therapy that can effectively be used in the prevention or treatment of RIII.

Investigating the Size Effect of Metal-Organic Frameworks in Drug Delivery and Anticancer Properties.

Here, we show particle size-dependent therapeutic efficacy with a Zn-based metal-organic framework (MOF). The size of MOFs was tuned in specific ranges (∼100, 200, and 300 nm) built upon the manipulation of synthetic conditions. X-ray photoelectron spectroscopy, infrared, PXRD, and dynamic light scattering and scanning electron microscopy analyses were used to identify the synthesized structures. The various analyses revealed minimal changes in the molecular properties of these structures regardless of their size, confirming our hypothesis regarding the preservation of the identity of MOF nanoparticles despite size variation. The synthesized carriers undergo structure relative destruction in response to a weak acidic tumor microenvironment, and this relative degradation allows the release of the Nimesulide drug into the environment. Interestingly, anticancer studies resulting in SKBR3 (Human breast cancer cell) cells indicate that the different sizes resulted in various inhibition capacities against cancer cells. This work shows the importance of optimizing the geometry of the drug carrier, such as size and shape, to achieve the highest cellular uptake and therapeutic performance. Besides, theoretical studies were carried out using B3LYP/6-31G (d,p) and density functional theory methods to more consider the drug adsorption mechanism.

Tailored Metal-Based Catalysts: A New Platform for Targeted Anticancer Therapies.

Innovative strategies for targeted anticancer therapies have gained significant momentum, with metal complexes emerging as tunable catalysts for more effective and safer treatments. Rational design and engineering of metal complexes enable the development of tailored molecular structures optimized for precision oncology. The strategic incorporation of metal complex catalysts within combinatorial therapies amplifies their anticancer properties. This perspective highlights the advancements in synthetic strategies and rational design since 2019, showing how tailored metal catalysts are optimized by designing structures to release or in situ synthesize active drugs, leveraging the target-specific characteristics to develop more precise cancer therapies. This review explores metal-based catalysts, including those conjugated with biomolecules, nanostructures, and metal-organic frameworks (MOFs), highlighting their catalytic activity in biological environments and their in vitro/in vivo performance. To sum up, the potential of metal complexes as catalysts to reshape the landscape of anticancer therapies and foster novel avenues for therapeutic advancement is emphasized.

A dual-pathway pyroptosis inducer based on Au-Cu2-xSe@ZIF-8 enhances tumor immunotherapy by disrupting the zinc ion homeostasis.

The regulation of intracellular ionic homeostasis to trigger antigen-specific immune responses has attracted extensive interest in tumor therapy. In this study, we developed a dual-pathway nanoreactor, Au-Cu2-xSe@ZIF-8@P18 NPs (ACS-Z-P NPs), which targets danger-associated molecular patterns (DAMPs) and releases Zn2+ and reactive oxygen species (ROS) within the tumor microenvironment (TME). Zn2+ released from the metal-organic frameworks (MOFs) was deposited in the cytoplasm, leading to aberrant transcription levels of intracellular zinc-regulated proteins and DNA damage, thereby inducing pyroptosis and immunogenic cell death (ICD) dependent on caspase1/gasdermin D (GSDMD) pathway. Furthermore, upon laser irradiation, ACS-Z-P NPs could break through the limitations of inherent defects of immunosuppression in TME, enhance ROS generation through a Fenton-like reaction cascade, which subsequently triggered the activation of inflammatory vesicles and the release of damage-associated molecular patterns (DAMPs). This cascade effect led to the amplification of pyroptosis and immunogenic cell death (ICD), thereby remodeling the immunosuppressed TME. Consequently, this process improved dendritic cell (DC) antigen presentation and augmented anti-tumor T-cell responses, effectively initiating antigen-specific immune responses and further enhancing pyroptosis and ICD. This study explores the therapeutic properties of these mechanisms in detail. STATEMENT OF SIGNIFICANCE: The synthesized Au-Cu2-xSe@ZIF-8@P18 nanoparticles (ACS-Z-Ps) can effectively enhance the body's immune response by regulating zinc ion levels within cells. This regulation leads to abnormal levels of zinc-regulated protein transcription and DNA damage, which induces cellular pyroptosis. As a result, antigen presentation to dendritic cells (DCs) is improved, and anti-tumor T-cell responses are enhanced. The ACS-Z-P NPs overcome the limitations of ROS deficiency and immunosuppression in the tumor microenvironment by using H2O2 in the tumor microenvironment through a Fenton-like reaction. This leads to an increased production of ROS and O2, remodeling of the immunosuppressed tumor microenvironment, and enhanced induction of cell pyroptosis and immunogenic cell death. ACS-Z-P NPs targeted B16 cells using the photosensitizer P18 in combination with PDT treatment. This approach significantly inhibited the proliferation of B16 cells and effectively inhibited tumor growth.

Synergistic bactericidal effect of antimicrobial peptides and copper sulfide-loaded zeolitic imidazolate framework-8 nanoparticles with photothermal therapy.

Antimicrobial resistance (AMR) has emerged as a significant threat to human health. Antimicrobial peptides (AMPs) have proven to be an effective strategy against antibiotic-resistant bacteria, given their capacity to swiftly disrupt microorganism membranes and alter cell morphology. A common limitation, however, lies in the inherent toxicity of many AMPs and their vulnerability to protease degradation within the body. Photothermal therapy (PTT) stands out as a widely utilized approach in combating antibiotic-resistant bacterial infections, boasting high efficiency and non-invasive benefits. To enhance the stability and antibacterial efficacy of AMPs, a novel approach involving the combination of AMPs and PTT has been proposed. This study focuses on the encapsulation of At10 (an AMP designed by our group), and copper sulfide nanoparticles (CuS NPs) within zeolitic imidazolate framework-8 (ZIF-8) to form nanocomposites (At10/CuS@ZIF-8). The encapsulated CuS NPs exhibit notable photothermal properties upon exposure to near-infrared radiation. This induces the cleavage of ZIF-8, facilitating the release of At10, which effectively targets bacterial membranes to exert its antibacterial effects. Bacteria treated with At10/CuS@ZIF-8 under light radiation exhibited not only membrane folding and intracellular matrix outflow but also bacterial fracture. This synergistic antibacterial strategy, integrating the unique properties of AMPs, CuS NPs, and pH responsiveness of ZIF-8, holds promising potential for widespread application in the treatment of bacterial infections.

A metal-organic nanoframework for efficient colorectal cancer immunotherapy by the cGAS-STING pathway activation and immune checkpoint blockade.

Immunotherapy has shown marked progress in promoting systemic anti-colorectal cancer (CRC) clinical effects. For further effectively sensitizing CRC to immunotherapy, we have engineered a pH-sensitive zeolitic imidazolate framework-8 (CS/NPs), capable of efficient cGAS-STING pathway activation and immune checkpoint blockade, by encapsulating the chemotherapeutic mitoxantrone (MTX) and immunomodulator thymus pentapeptide (TP5) and tailoring with tumor-targeting chondroitin sulfate (CS). In this nanoframework, CS endows CS/NPs with specific tumor-targeting activity and reduced systemic toxicity. Of note, the coordinated Zn2+ disrupts glycolytic processes and downregulates the expression of glucose transporter type 1 (GLUT1), thus depriving the cancer cells of their energy. Zn2+ further initiates the adenosine 5'-monophosphate activated protein kinase (AMPK) pathway, which leads to PD-L1 protein degradation and sensitizes CRC cells to immunotherapy. Moreover, the damaged double-stranded DNA during MTX treatment activates the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, which works together with TP5 induced the proliferation and differentiation of T lymphocytes and dendritic cells to further enhance the anti-CRC immune response. Therefore, CS/NPs efficiently sensitize cells to chemotherapy and stimulate systemic antitumor immune responses both in vitro and in vivo, representing a promising strategy to increase the feasibility of CRC immunotherapy.

Triple-negative breast cancer treatment with core-shell Magnetic@Platinium-Metal organic framework/epirubicin nano-platforms for chemo-photodynamic based combinational therapy: A review.

The combination of chemotherapy and photodynamic therapy (PDT), enabled by core-shell nano-platforms, is a promising method to improve cancer therapy by overcoming hypoxia and boosting drug penetration in breast tumor. Core-shell magnetic (iron oxide: Fe3O4)@platinum-metal organic framework/epirubicin (abbreviated as M@Pt-MOF/EPI) nano-platform is considered an effective cancer therapeutic agent. Relatively small particle size, round shape, and specific response to pH, are the key features of these nanomaterials to be used as promising therapeutic agents. Chemotherapy and photodynamic therapy, when applied in addition to the anticancer effects of nanomaterials, further enhance the therapeutic efficacy. The extensive use, utilization, and efficacy of Core-Shell Magnetic@Platinium-Metal Organic Framework/epirubicin Nano-Platforms for chemo-photodynamic combination therapy in the treatment of several cancers, including triple-negative breast cancer, are examined in this in-depth investigation.

Engineering a porphyrin COFs encapsulated by hyaluronic acid tumor-targeted nanoplatform for sequential chemo-photodynamic multimodal tumor therapy.

Numerous barriers hinder the entry of drugs into cells, limiting the effectiveness of tumor pharmacotherapy. Effective penetration into tumor tissue and facilitated cellular uptake are crucial for the efficacy of nanotherapeutics. Photodynamic therapy (PDT) is a promising approach for tumor suppression. In this study, we developed a size-adjustable porphyrin-based covalent organic framework (COF), further modified with hyaluronic acid (HA), to sequentially deliver drugs for combined chemo-photodynamic tumor therapy. A larger COF (P-COF, approximately 500 nm) was loaded with the antifibrotic drug losartan (LST) to create LST/P-COF@HA (LCH), which accumulates at tumor sites. After injection, LCH releases LST, downregulating tumor extracellular matrix (ECM) component levels and decreasing collagen density, thus reducing tumor solid stress. Additionally, the reactive oxygen species (ROS) generated from LCH under 660 nm laser irradiation induce lipid peroxidation of cell membranes. Owing to its larger particle size, LCH primarily functions extracellularly, paving the way for subsequent treatments. Following intravenous administration, the smaller COF (p-COF, approximately 200 nm) loaded with doxorubicin (DOX) and modified with HA (DOX/p-COF@HA, DCH) readily enters cells in the altered microenvironment. Within tumor cells, ROS generated from DCH facilitates PDT, while the released DOX targets cancer cells via chemotherapy, triggered by disulfide bond cleavage in the presence of elevated glutathione (GSH) levels. This depletion of GSH further enhances the PDT effect. Leveraging the size-tunable properties of the porphyrin COF, this platform achieves a multifunctional delivery system that overcomes specific barriers at optimal times, leading to improved outcomes in chemo-photodynamic multimodal tumor therapy in vivo.

One-Pot Synthesis of a pH-Sensitive MOF Integrated with Glucose Oxidase for Amplified Tumor Photodynamic/Photothermal Therapy.

Photothermal therapy (PTT) and photodynamic therapy (PDT) provide targeted approaches to cancer treatment, but each therapy has inherent limitations such as insufficient tissue penetration, uneven heat distribution, extreme hypoxia, and overexpressed HSP90 in tumor cells. To address these issues, herein, by encapsulating the IR780 dye and glucose oxidase (GOx) enzyme within ZIF-8 nanoparticles, we created a versatile system capable of combining photodynamic and enhanced photothermal therapy. The integration of the IR780 dye facilitated the generation of reactive oxygen species and hyperthermia upon light activation, enabling dual-mode cancer cell ablation. Moreover, GOx catalyzes the decomposition of glucose into gluconic acid and hydrogen peroxide, leading to the inhibition of ATP production and downregulation of heat shock protein 90 (HSP90) expression, sensitizing cancer cells to heat-induced cytotoxicity. This synergistic combination resulted in significantly improved therapeutic outcomes. Both in vitro and in vivo results validated that the nanoplatform demonstrated superior specificity and favorable therapeutic responses. Our innovative approach represents a promising strategy for overcoming current limitations in cancer treatments and offers the potential for clinical translation in the future.

ZIF-8 as a pH-Responsive Nanoplatform for 5-Fluorouracil Delivery in the Chemotherapy of Oral Squamous Cell Carcinoma.

5-fluorouracil (5-FU), a chemotherapeutic agent against oral squamous cell carcinoma (OSCC), is limited by poor pharmacokinetics and toxicity. The pH-sensitive zeolite imidazolate framework-8 (ZIF-8) may increase the selectivity and length of 5-FU released into the acidic tumor microenvironment. This study examined the in vitro 5-FU absorption and release profiles of ZIF-8, and then progressed to cytotoxicity assays using the OSCC primary cell line SCC7. The 5-FU loading capacity of ZIF-8 was calculated with UV-vis spectroscopy (λ = 260 nm). 5-FU release was quantified by submerging 5-FU@ZIF-8 in pH 7.4 and 5.5 acetate buffer over 48 h. For the cytotoxicity assays, 5-FU, ZIF-8, and 5-FU@ZIF-8 were added to SCC7 cultures at 25, 50, and 100 µg/mL. Cell viability was assessed through toluidine blue staining and further quantified through transcriptomic RNA sequencing. ZIF-8 stabilized at a maximum absorption of 2.71 ± 0.22 mg 5-FU, and released 0.66 mg more 5-FU at pH 5.5 than 7.4 for at least 72 h. The cytotoxicity assays showed that 5-FU@ZIF-8 had a synergistic inhibitory effect at 50 µg/mL. The RNA sequencing analysis further revealed the molecular targets of 5-FU@ZIF-8 in SCC7. 5-FU@ZIF-8 may release 5-FU based on the pH of the surrounding microenvironments and synergistically inhibit OSCC.