Release Of Doxorubicin Research Articles

Research on the Inhibitory Effect of Doxorubicin-loaded Liposomes Targeting GFAP for Glioma Cells.

Glioma is the most common and devastating brain tumor. In recent years, doxorubicin (DOX) is one of the drugs used in the treatment of gliomas, but it has side effects and poor clinical outcomes. Therefore, the delivery of drugs to the tumor site by targeted transport is a new approach to tumor treatment. This study focuses on the anti-tumor effects of GFAP-modified drug-carrying liposomes loaded with DOX (GFAP-DOX-LPs) on gliomas. GFAP-DOX-LPs were prepared by solvent evaporation method. After characterization analysis of GFAP-DOX-LPs, the encapsulation efficiency, the drug loading capacity and in vitro release performance were determined. Then, the MTT method was used to investigate the cytotoxicity and proliferative behavior of U251 and U87 cell lines. After that, flow cytometry was used to investigate the effect of the drug administration group on tumor cell apoptosis. Eventually, the anti-tumor activity was tested in vivo. The average particle size of GFAP-DOX-LPs was determined to be 116.3 ± 6.2 nm, and the average potential was displayed as 22.8 ± 7.2 mv. Besides, the morphology of the particle indicated a spherical shape. The encapsulation rate and drug loading were calculated and determined, which were 91.84 ± 0.41% and 9.27 ± 0.55%. In an acidic medium, the DOX release rate reached about 87%. GFAP-DOX-LPs could target glioma cells with low cytotoxicity and inhibit glioma cell proliferation with high efficiency, resulting in promoting apoptosis. The anti-tumor effect of GFAP-DOX-LPs was significantly enhanced. At the same time, the number of GFAPpositive cells in tumor tissues was significantly lower after treatment. Therefore, the overall survival time could be significantly prolonged. The prepared GFAP-DOX-LPs had good targeting and glioma cell inhibition ability. This demonstrated the promising application of the prepared liposomes in tumor targeting, especially in the field of targeted drug delivery for the treatment of brain tumor.

Multifunctional ZnO@DOX/ICG-LMHP Nanoparticles for Synergistic Multimodal Antitumor Activity.

Multifunctional nanoparticles are of significant importance for synergistic multimodal antitumor activity. Herein, zinc oxide (ZnO) was used as pH-sensitive nanoparticles for loading the chemotherapy agent doxorubicin (DOX) and the photosensitizer agent indocyanine green (ICG), and biocompatible low-molecular-weight heparin (LMHP) was used as the gatekeepers for synergistic photothermal therapy/photodynamic therapy/chemotherapy/immunotherapy. ZnO was decomposed into cytotoxic Zn2+ ions, leading to a tumor-specific release of ICG and DOX. ZnO simultaneously produced oxygen (O2) and reactive oxygen species (ROS) for photodynamic therapy (PDT). The released ICG under laser irradiation produced ROS for PDT and raised the tumor temperature for photothermal therapy (PTT). The released DOX directly caused tumor cell death for chemotherapy. Both DOX and ICG also induced immunogenic cell death (ICD) for immunotherapy. The in vivo and in vitro results presented a superior inhibition of tumor progression, metastasis and recurrence. Therefore, this study could provide an efficient approach for designing multifunctional nanoparticles for synergistic multimodal antitumor therapy.

Modulation of macrophage polarity with carboxymethyl chitin gated hollow mesoporous silica nanoparticles for elevating anti-tumor chemotherapy

The weak immunity of tumors after chemotherapy could cause tumor metastasis and progression. Therefore, to overcome the dilemma of obvious immune deficiency caused by chemotherapy, a nanosystem (N-IL-12/DOX/α-TOS) consisted of thioketal (TK) bonds linked-hollow mesoporous silica nanoparticles (HMSNs) coated with carboxymethyl chitin (CMCH) by electrostatic interaction, and surface-functionalized glucose-regulated protein 78 binding peptide was prepared for loading doxorubicin (DOX), IL-12 and α-tocopheryl succinate (α-TOS). N-IL-12/DOX/α-TOS displayed a mean size of 275 nm after encapsulated DOX, IL-12 and α-TOS with loading contents of 2.04 × 10−4, 4.01 × 10−2 and 7.12 × 10−2, respectively. The drug-free nanoparticles (NPs) showed good biocompatibility to both 4 T1 cells and RAW264.7 macrophages. N-IL-12/DOX/α-TOS could achieve localized release of IL-12, DOX and α-TOS by pH and H2O2 trigger in the tumor microenvironment (TME). Moreover, the combined therapy by N-IL-12/DOX/α-TOS remarkably elevated the anti-tumor therapeutic efficacy, enhanced immune responses via promoting tumor-associated macrophage (TAM) polarization into tumoricidal M1 phenotypes, and decreased lung metastasis with reduced side effects. N-IL-12/DOX/α-TOS exhibited as a promising strategy for combining chemotherapy and local macrophage modulation-immunotherapy for anti-tumor therapy.

NIR-responsive carboxymethyl-cellulose hydrogels containing thioketal-linkages for on-demand drug delivery system

Near-infrared (NIR) light-responsive hydrogels have emerged as a highly promising strategy for effective anticancer therapy owing to the remotely controlled release of chemotherapeutic molecules with minimal invasive manner. In this study, novel NIR-responsive hydrogels were developed from reactive oxygen species (ROS)-cleavable thioketal cross-linkers which possessed terminal tetrazine groups to undergo a bio-orthogonal inverse electron demand Diels Alder click reaction with norbornene modified carboxymethyl cellulose. The hydrogels were rapidly formed under physiological conditions and generated N2 gas as a by-product, which led to the formation of porous structures within the hydrogel networks. A NIR dye, indocyanine green (ICG) and chemotherapeutic doxorubicin (DOX) were co-encapsulated in the porous network of the hydrogels. Upon NIR-irradiation, the hydrogels showed spatiotemporal release of encapsulated DOX (>96 %) owing to the cleavage of thioketal bonds by interacting with ROS generated from ICG, whereas minimal release of encapsulated DOX (<25 %) was observed in the absence of NIR-light. The in vitro cytotoxicity results revealed that the hydrogels were highly cytocompatible and did not induce any toxic effect on the HEK-293 cells. In contrast, the DOX + ICG-encapsulated hydrogels enhanced the chemotherapeutic effect and effectively inhibited the proliferation of Hela cancer cells when irradiated with NIR-light.

Preparation, Optimization and In vitro Evaluation of Doxorubicin-loaded into Hyaluronic Acid Coated Niosomes Against Breast Cancer.

Doxorubicin (DOX) is widely used against solid tumors. Niosomes are self-assembled nanocarriers of non-ionic surfactants. DOX loaded into cationic niosomes (DOX-Nio) was prepared via thin film hydration method. DOX-Nio was then decorated with a hyaluronic acid (DOX-HA-Nio) via electrostatic interaction. DOX-Nio and DOX-HA-Nio displayed a particle size of 120.0±1.02 and 182.9±2.3 nm, and charge of + 35.5±0.15 and -15.6±0.25 mV, respectively, with PDI < 0.3. DOX-HA-Nio showed a good stability regarding size and charge over 4 weeks at 4 °C and maintain their integrity after lyophilization. HPLC results showed a 94.1±4.2 % encapsulation efficiency of DOX with good entrapment and slow, prolonged DOX release even after 48 hrs. Cell viability assay showed an IC50 of 14.26 nM for the DOX-HA-Nio against MCF-7 cell line with micromolar IC50 results against CD-44 negative cell lines (NIH/3T3). DOX-HA-Nio was proven to be an effective, targeted nanocarrier for DOX against MCF-7 cell line.

Preparation and antitumor study of intelligent injectable hydrogel: Carboxymethyl chitosan–aldehyde gum Arabic composite graphene oxide hydrogel

In this study, we used polyaldehyde gum Arabic (OGA) and carboxymethyl chitosan (CMCS) as a gel matrix to form an injectable self-healing hydrogel by Schiff-base bonding. Further, graphene oxide (GO) was loaded with doxorubicin (DOX) to the hydrogel, which resulted in a CMCS-OGA/GO@DOX hydrogel. We achieved a DOX drug loading capacity of 43.80 ± 1.13 %. Rheological studies showed that GO hydrogels have improved mechanical properties. The in vitro release profile showed pH responsiveness with 88.21 % DOX release at pH 5.5. Biocompatibility studies showed that the hydrogel composition had good cytocompatibility with L929 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed a cell survival rate of 93.88 % within 48 h. The DOX-loaded hydrogel exhibited higher cell mortality in breast cancer cells (4 T1), with an inhibition rate of 79.4 % at 48 h. Acridine orange/ethidium bromide staining experiments on 4 T1 cells showed that when loaded with the same DOX concentration, the hydrogel significantly reduced the toxic effects on normal cells, whereas it had significant cytotoxic effects on cancer cells. This result indicates that the prepared GO hydrogel drug delivery system can serve as a novel approach for localized breast cancer treatment.

Synthesis of cationic gel-coated hydroxyapatite composites for pH- and thermo-responsive drug delivery in tumor microenvironments

Nanomedicine has gained a significant attention in biomedical science and engineering. It involves design and applications of engineered composites for targeted delivery, diagnostics, imaging, and therapeutic efficacy assessment. Herein, multi-stimuli responsive doxorubicin (DOX) loaded composites were prepared and used for controlled anticancer drug release for antitumor efficacy. In this study, we synthesized the HAp@PP composites by coating Pluronic® P123 and branched polyethylenimine (PP nanogel) on hydroxyapatite (HAp) particles. In-vitro cytotoxicity tests emphasized that HAp@PP composites presented a cell viability of more than 80 % before DOX loading. The fabricated HAp@PP–DOX composites indicated a pH-/thermo-reliant DOX release under tumor microenvironment conditions. Furthermore, the Korsmeyer-Peppas kinetic model yielded the best fit for the release of DOX under the conditions studied. The in-vitro assessment revealed that HAp@PP–DOX had a higher effect that free DOX, with a cell viability less than 25 % and 15 %, respectively, at a DOX concentration of 50 μg/mL. In the context of cancer treatment, the composites have the potential to be more effective than traditional chemotherapy by delivering drugs efficiently.

Visible light and pH-responsive star copolymer and doxorubicin-polymer conjugate micelles for combination drug delivery and bioimaging

Amphiphilic 3-arm star copolymer containing visible light-cleavable BODIPY group and pH-responsive imine bonds at the junction of hydrophilic poly(ethylene glycol) (PEG) and two poly(ε-caprolactone) (PCL) arms was synthesized by the combination of ring-opening polymerization (ROP) and click chemistry. The formation and stimuli-responsive disruption of micelles were analyzed using dynamic light scattering and transmission electron microscopy. Dual stimuli-responsive release of anticancer drugs Doxorubicin (Dox) and Camptothecin (CPT) from the micelles was studied. Micellar assemblies containing Dox conjugated to PEG-BODIPY through imine bonds were prepared and controlled release of Dox in response to visible light and pH was shown. CPT and Dox-loaded star copolymer micelles as well as CPT loaded Dox-conjugated micelles were used in cellular uptake studies on MDA-MB 231 cells, and the synergistic effect of the two stimuli on the release of the two drugs was demonstrated inside the cells. Micellar assemblies also showed excellent bioimaging properties in the cellular uptake studies.

A chemo/chemodynamic nanoparticle based on hyaluronic acid induces ferroptosis and apoptosis for triple-negative breast cancer therapy

Triple-negative breast cancer (TNBC) poses a serious threat to women's life and health due to its high malignancy, strong invasiveness, and propensity for early recurrence and metastasis. Therefore, there is an urgent need to develop a highly effective and low-toxic TNBC treatment scheme to enhance the anti-cancer efficacy and prolong the survival of patients. In this work, we designed and synthesized a chemodynamic therapy (CDT) agent (HA-Fc-Mal). The chemo/chemodynamic (CT/CDT) nanoparticle (HCM@DOX) based on hyaluronic acid induces ferroptosis and apoptotic for TNBC therapy was constructed via self-assembled of HA-Fc-Mal and doxorubicin (DOX). HCM@DOX orderly realized the TNBC targeting, controlled DOX release, GSH depletion and induce ROS erupt. In vivo and in vitro experiments confirmed that HCM@DOX inhibited the growth of 4 T1 tumors through ferroptosis and apoptosis, and the tumor inhibition rate was as high as 81.87 %. In addition, HCM@DOX significantly inhibited lung metastasis and exhibited excellent biosafety. Overall, our findings offer a new strategy for TNBC therapy using a CT/CDT nanoparticle that induces ferroptosis and apoptosis.

Metal-polyphenol network coated photothermal nanocarriers for pH-activated drug delivery

The combination of photothermal and chemotherapy is a promising strategy for the synergistic inhibition of tumor cells. By exploiting the tumor microenvironment, chemotherapeutic drugs can target the tumor site, thereby enhancing their efficacy. This study focused on the development of nanodrugs, aiming to harness the synergistic photothermal and chemotherapy capabilities for enhanced anti-tumor effects. The core material was made of copper sulfide (CuS), which possesses photothermal conversion properties, while doxorubicin (DOX) was loaded on mesoporous polydopamine (MPDA). The drug-loaded nanoparticles were then encapsulated in acid-sensitive tannic acid and an Fe complex (TA-Fe). The photothermal conversion properties, drug loading, and release of DOX from CuS-MPDA-DOX@TA-Fe were then investigated. The results showed that DOX had an encapsulation ratio of 82.2 % and a release ratio of 43.49 % in an acidic environment (pH 5.2). In vitro studies showed that CuS-MPDA-DOX@TA-Fe triggered by NIR effectively inhibited tumor cell proliferation and that the tumor cells showed suitable levels of nanoparticle uptake. The results thus show that CuS-MPDA-DOX@TA-Fe nanodrugs could be utilized as a promising therapeutic strategy for cancer treatment with synergistic photothermal/chemotherapeutic anti-tumor effects.

Photo-induced drug release at interfaces with arylazopyrazoles.

Smart responsive materials have spurred the progress in high-precision drug delivery. Enormous attention has been given to characterizing drug release in bulk aqueous solutions, however, aqueous-hydrophobic interfaces are vital components of biological systems which serve as the point of entry into cells. These interfaces are involved in many key biomolecular interactions, and while the potential for drug molecules to adsorb to these interfaces is recognized, their specific role in the context of drug release remains largely unexplored. We present a fundamental investigation on the release of encapsulated drugs at the air-water interface as a representative model to mimic the organic/aqueous interface of cells. Combining the advantages of light as an external stimulus and the superiority of arylazopyrazoles (AAP) over conventional azobenzene photoswitches, we report a micellar nanocarrier for the capture and release of the chemotherapeutic drug doxorubicin. Using a powerful combination of interface-sensitive techniques such as the Langmuir-Blodgett technique, surface tensiometry, and the interface-specific vibrational sum-frequency generation spectroscopy, we demonstrate the photoresponsive release of doxorubicin encapsulated in the micelles of AAP photosurfactants to the air-water interface. Complementary fluorescence measurements corroborate additional drug release in bulk aqueous solutions.

Dual stimuli-responsive biotinylated polymer-drug conjugate for dual drug delivery.

Stimuli-responsive nanoscale polymer-drug conjugates are one of the most promising alternatives in the realm of advanced therapeutics, rendering several characteristics such as spatio-temporal control over drug release, reduced off-target toxicity, enhanced bioavailability, and longer blood circulation time of the drug. Fostered by the aforementioned conceptualization, our quest to develop an ideal polymer-drug conjugate has originated the present investigation of developing a reactive oxygen species (ROS) and esterase-responsive self-assembled polymer-drug (chlorambucil, CBL) conjugate with biotin pendants (DP2) for cancer cell targeting, surrogating another antineoplastic drug, doxorubicin (DOX) via physical encapsulation (DP2@DOX). The ROS and esterase trigger not only released the covalently stitched CBL but also resulted in DOX release by dismantling the amphiphilic balance of the nanoaggregates. Biotinylation-mediated enhancement of cellular uptake of DP2@DOX was reflected in the synergistic anticancer activity of both the drugs (CBL and DOX) in HeLa cells (biotin receptor-positive cells) compared to HEK 293T cells (biotin receptor-negative cells). Furthermore, the selective internalization of the fluorophore-tagged DOX-loaded polymer (DP4@DOX) in HeLa cells compared to HEK 293T cells was confirmed by confocal microscopy and flow cytometry. In summary, the present investigation demonstrates a state-of-the-art self-assembled polymer-drug conjugate as a next-generation dual stimuli-responsive drug delivery vehicle.

Advanced hybrid silica nanoparticles with pH-responsive diblock copolymer brushes: optimized design for controlled doxorubicin loading and release in cancer therapy.

This study delves into the development, characterization, and application of modified mesoporous silica nanoparticles (MSNs) for targeted drug delivery in cancer therapy. MSNs were functionalized with poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) and poly(glycidyl methacrylate) (PGMA), and further modified with cross-linkers DAE and Ornithine. Characterization using FT-IR, SEM, TEM, DLS, and XPS confirmed the successful surface modifications, revealing particle sizes primarily within the 63-94 nm range. The MSNs demonstrated a pH-responsive behavior, crucial for smart drug delivery. Loading and release studies using Doxorubicin (DOX) showed a controlled release, with an 8 μg mg-1 loading capacity. Cytotoxicity assays on Caco2 colon cancer cells revealed that unloaded nano-systems, at concentrations above 45 μM, resulted in approximately 60% cell death, indicating inherent anti-cancer properties. However, variations in cytotoxic effects were observed in drug-loaded MSNs, with some modifications showing reduced anti-cancer activity. These findings highlight the potential of MSNs in drug delivery and cancer treatment, emphasizing the importance of nanoparticle design in therapeutic efficacy.

ATP-responsive copper(II)-doped ZIF-nanoparticles for synergistic cancer therapy: combining cuproptosis and chemo/chemodynamic therapy.

Cancer, a pressing global health challenge, is characterized by its rapid onset and high mortality rates. Conventional treatment methods prove insufficient in achieving the desired therapeutic outcomes, underscoring the critical need to identify an effective and safe approach for cancer treatment. In this study, a copper-doped nanoparticle known as Cu2+-DOX@ZIF-90 is designed by incorporating copper(II) (Cu(II)) and encapsulating doxorubicin (DOX) within ZIF-90. Leveraging the elevated ATP levels in cancer cells relative to normal cells, Cu2+-DOX@ZIF-90 undergoes intracellular degradation, leading to the release of DOX and Cu(II). DOX, a traditional chemotherapy drug for clinical use, induces apoptosis in cancer cells. Cu(II) interacts with glutathione (GSH) to generate Cu(I), catalyzing H2O2 to produce ˙OH, thereby prompting apoptosis in cancer cells. Concurrently, the reduction of GSH enhances the therapeutic effect of chemodynamic therapy (CDT). Furthermore, Cu(II) triggers the aggregation of lipoylated mitochondrial proteins, leading to the formation of DLAT oligomers and ultimately promoting cuproptosis in cancer cells. In vivo experimental findings demonstrate that Cu2+-DOX@ZIF-90 does not cause damage to normal tissues and organs in tumor-bearing mice, with a notable tumor inhibition rate of 86.18%. This synergistic approach, combining chemotherapy, CDT, and cuproptosis, holds significant promise for the effective and safe treatment of cancer.

A potent multifunctional ZIF-8 nanoplatform developed for colorectal cancer therapy by triple-delivery of chemo/radio/targeted therapy agents.

Multimodal cancer therapy has garnered significant interest due to its ability to target tumor cells from various perspectives. The advancement of novel nano-delivery platforms represents a promising approach for improving treatment effectiveness while minimizing detrimental effects on healthy tissues. This study aimed to develop a multifunctional nano-delivery system capable of simultaneously delivering an anti-cancer drug, a radiosensitizer agent, and a targeting moiety (three-in-one) for the triple combination therapy of colorectal cancer (CRC). This unique nano-platform, called Apt-PEG-DOX/ZIF-8@GQD, encapsulated both doxorubicin (DOX) and graphene quantum dots (GQDs) within the zeolitic imidazolate framework-8 (ZIF-8). To enhance the safety and anti-cancer potential of the platform, heterobifunctional polyethylene glycol (PEG) and an epithelial cell adhesion molecule (EpCAM) aptamer were conjugated with the system, resulting in the formation of targeted Apt-PEG-DOX/ZIF-8@GQD NPs. The physical and chemical characteristics of Apt-PEG-DOX/ZIF-8@GQD were thoroughly examined, and its therapeutic efficacy was evaluated in combination with radiotherapy (RT) against both EpCAM-positive HT-29 and EpCAM-negative CHO cells. Furthermore, the potential of Apt-PEG-DOX/ZIF-8@GQD as a tumor-specific, radio-enhancing, non-toxic, and controllable delivery system for in vivo cancer treatment was explored using immunocompromised C57BL/6 mice bearing human HT-29 tumors. The large surface area of ZIF-8 (1013 m2 g-1) enabled successful loading of DOX with an encapsulation efficiency of approximately ∼90%. The synthesis of Apt-PEG-DOX/ZIF-8@GQD resulted in uniform particles with an average diameter of 100 nm. This targeted platform exhibited rapid decomposition under acidic conditions, facilitating an on-demand release of DOX after endosomal escape. In vitro experiments revealed that the biocompatible nano-platform induced selective toxicity in HT-29 cells by enhancing X-ray absorption. Moreover, in vivo experiments demonstrated that the therapeutic efficacy of Apt-PEG-ZIF-8/DOX@GQD against HT-29 tumors was enhanced through the synergistic effects of chemotherapy, radiotherapy, and targeted therapy, with minimal side effects. The combination of Apt-PEG-DOX/ZIF-8@GQD with RT as a multimodal therapy approach demonstrated promising potential for the targeted treatment of CRC and enhancing therapeutic effectiveness. The co-delivery of DOX and GQD using this nano-platform holds great promise for improving the outcome of CRC treatment.

A Novel pH-sensitive Nanocomposite Based on Graphene Oxide for Improving Doxorubicin Release.

Doxorubicin (DOX) as a chemotherapeutic drug has been widely used for treatment of cancer but because of adverse side effects of this drug, different drug delivery systems have been tested. One of them has been immobilization of DOX on the graphene oxide (GO) sheets through non-covalent interactions (GO-DOX) with high efficiency however the release was very low and slow due to strong forces between DOX and GO. The aim of this research was to increase the release of DOX and this goal was achieved through the covalent binding of DOX to the GO-poly(ethyleneimine) 2KDa conjugate. A novel nanocarrier for delivering DOX was fabricated using GO as a basic plane for conjugating and assembling other compounds. DOX was attached to GO-poly(ethyleneimine) 2KDa conjugate via</i> a linker containing hydrazide bond. Drug loading and release was investigated at pH 7.5 and pH 5.5. Cytotoxicity was determined by MTT on MCF7 cells and compared with previous nanocarrier. The fabrication of the nanocarrier and the covalent attachment of DOX to the nanocarrier were confirmed through FT-IR spectroscopy. The capacity of nanocarrier to load drug was as high as 383%. 96% of initial drug was loaded in the nanocarrier. The weight percentage of the drug in the nanocarrierdrug conjugate was 79%. Release of drug at pH 5.5 was two times more than release at pH 7.5 and this evidence supports conjugation of DOX to nanocarrier through hydrazide bond and pH-sensitivity of related bond. Because of the reliable results, ease of operation, safety and high reproducibility, MTT was chosen to evaluate the cytotoxicity of samples. Nanocarrier didn't show significant toxicity even at high concentrations. IC50 value for chemically-bound DOX to hydrazide-containing GO nanocomposite was 9.5 μg/ml whereas the IC50 value for GO-DOX was 39 μg/ml after 72 h. Loading of DOX via hydrazide bond was as low as 4% versus near 75% physical loading of drug while hydrazide bondcontaining nanocomposite was 4 to 6 fold more toxic than GO-DOX. Based on the obtained data, the covalent attachment of DOX to the nanocarrier through hydrazide linkers was an interesting idea that increased drug release and toxicity despite much lower percentage of covalent attachment compared to non-covalent immobilization. As could be concluded from this study, nanocarriers based on hydrazide bond could be a good candidate for drug delivery.

A hierarchically acidity-unlocking nanoSTING stimulant enables cascaded STING activation for potent innate and adaptive antitumor immunity.

Rationale: Neoadjuvant chemotherapy (NAC) has been recognized as an indispensable strategy for advanced malignancies. Nevertheless, the enhancement of overall patient survival in NAC recipients has encountered challenges due to the limited sustainability of its efficacy and the inability to prevent postoperative tumor recurrence and metastasis. Methods: We devise a hierarchically unlocking nanoSTING stimulant liposome (AUG) as a neoadjuvant chemoimmunotherapy agent in the debulking of tumors prior to surgery and prevention of postoperative tumor recurrence and metastasis by simultaneously activating innate and adaptive antitumor immune responses. In the weakly acidic tumor microenvironment, the hydrazone bond within AUG is initially cleaved, leading to the release of a cyclic seven-membered ring containing tertiary amine that serve to activate the stimulator of interferon genes (STING) pathway. Following this, AUG undergoes degradation within lysosomes, facilitating the release of doxorubicin and ultimately inducing immunogenic cell death along with leakage of double-stranded DNA into the cytoplasm. Results: The hierarchically acidity-unlocking pattern enables cascaded STING activation, achieving over 90% tumor growth inhibition in subcutaneous xenograft model and preventing 75% of mice from postsurgical metastasis or recurrence when combined with immune checkpoint inhibitors. Conclusion: Our strategy highlights the potency of AUG as a neoadjuvant paradigm for presurgical tumor debulking and as a preventive measure against postoperative tumor recurrence and metastasis.

Controlled release of doxorubicin from gelatin-based nanoparticles: theoretical and experimental approach

Doxorubicin (DOX), a well-known chemotherapeutic agent, is extensively used for cancer therapy.

Metal organic framework coated vesicular nano-aggregates: an intelligent ‘vehicle’ for sustained and leakage proof release of doxorubicin

ZIF-8 coated ionic liquid based vesicular nano-aggregates as drug vehicle for the chemotherapeutic drug doxorubicin in cancer treatment.

Active targeted delivery of theranostic thermo/pH dual-responsive magnetic Janus nanoparticles functionalized with folic acid/fluorescein ligands for enhanced DOX combination therapy of rat glioblastoma.

Doxorubicin (DOX), a chemotherapy drug, has demonstrated limited efficacy against glioblastoma, an aggressive brain tumor with resistance attributed to the blood-brain barrier (BBB). This study aims to overcome this challenge by proposing the targeted delivery of magnetic Janus nanoparticles (MJNPs) functionalized with folic acid ligands, fluorescent dye, and doxorubicin (DOX/MJNPs-FLA). The properties of these nanoparticles were comprehensively evaluated using bio-physiochemical techniques such as Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), zeta potential analysis, high-resolution transmission electron microscopy (HR-TEM), vibrating sample magnetometry (VSM), fluorescence microscopy, MTT assay, hemolysis assay, and liver enzyme level evaluation. Dual-controlled DOX release was investigated under different pH and temperature conditions. Additionally, the impact of DOX/MJNPs-FLA on apoptosis induction in tumor cells, body weight, and survival time of cancerous animals was assessed. The targeted delivery system was assessed using C6 and OLN-93 cell lines as representatives of cancerous and healthy cell lines, respectively, alongside Wistar rat tumor-bearing models. Results from Prussian blue staining and confocal microscopy tests demonstrated the effective targeted internalization of MJNPs-FLA by glioblastoma cells. Additionally, we investigated the biodistribution of the nanoparticles utilizing fluorescence imaging techniques. This enabled us to track the distribution pattern of MJNPs-FLA in vivo, shedding light on their movement and accumulation within the biological system. Furthermore, the combination of chemotherapy and magnetic hyperthermia exhibited enhanced efficacy in inducing apoptosis, as evidenced by the increase of the pro-apoptotic Bax gene and a decrease in the anti-apoptotic Bcl-2 gene. Remarkably, this combination treatment did not cause any hepatotoxicity. This study highlights the potential of DOX/MJNPs-FLA as carriers for therapeutic and diagnostic agents in the context of theranostic applications for the treatment of brain malignancies. Additionally, it demonstrates the promising performance of DOX/MJNPs-FLA in combination treatment through passive and active targeting.