Release Of Doxorubicin Research Articles

Self-propelled enzyme-controlled IR-mesoporous silica Janus nanomotor for smart delivery

Here, we report the preparation of a novel Janus nanoparticle with opposite Ir and mesoporous silica nanoparticles through a partial surface masking with toposelective modification method. This nanomaterial was employed to construct an enzyme-powered nanomachine with self-propulsion properties for on-command delivery. The cargo-loaded nanoparticle was provided with a pH-sensitive gate and unit control at the mesoporous face by first attaching boronic acid residues and further immobilization of glucose oxidase through reversible boronic acid esters with the carbohydrate residues of the glycoenzyme. Addition of glucose leads to the enzymatic production of H2O2 and gluconic acid, being the first compound catalytically decomposed at the Ir nanoparticle face producing O2 and causing the nanomachine propulsion. Gluconic acid leads to a pH reduction at the nanomachine microenvironment causing the disruption of the gating mechanism with the subsequent cargo release. This work demonstrates that enzyme-mediated self-propulsion improved release efficiency being this nanomotor successfully employed for the smart release of Doxorubicin in HeLa cancer cells.

Hollow-structured covalent organic framework decorated with FA-PEG: A biocompatible nanocarrier for targeted and pH-responsive release of doxorubicin

Hollow nanostructures hold great promise for drug delivery applications due to their considerable capabilities for efficient drug encapsulation alongside distinct physicochemical attributes. Herein, an imine-linked hollow nanosphere covalent organic framework (COF) with high surface area and well-structured porosity was developed serving as a versatile drug delivery system (DDS) to achieve targeted and effective delivery of doxorubicin (DOX) as a chemotherapeutic agent. The production of COF hollow nanoparticles included the use of a heterogeneous nucleation and growth method, followed by the subsequent encapsulation of DOX. Following this, the nanoparticles underwent functionalization with folate-poly (ethylene glycol)-amine (FA-PEG) using a bonding defect strategy. An in vitro cytotoxicity assay and flow cytometry study against FR-negative HEK293 and FR-positive MCF7 cells were performed, revealing that FA-PEG-functionalized HCOF exhibited a unique targeting effect on cancer cells, surpassing the impact of DOX@HCOF on FR-positive MCF7 cancer cells. Additionally, the hollow architecture of the COF is engineered to undergo disintegration selectively under conditions of cancer cell pH, facilitating the comprehensive release of DOX. The pH-responsive and tumor-targeted attributes of the DOX@HCOF-PEG-FA open new avenues for incorporating structural engineered HCOFs as a promising drug carrier capable of regulating drug release and augmenting therapeutic efficacy.

Biodegradable chitin nanofiber-alginate dialdehyde hydrogel: An injectable, self-healing scaffold for anti-tumor drug delivery

Injectable hydrogels fabricated from natural polymers have attracted increasing attentions for their potential in biomedical application owing to the biocompatibility and biodegradability. A new class of natural polymer based self-healing hydrogel is constructed through dynamic covalent bonds. The injectable self-healing hydrogels are fabricated by introducing alginate aldehyde to form Schiff base bonds with the chitin nanofibers. These hydrogels demonstrate excellent self-healing properties, injectability, and pH-responsive sol-gel transition behaviors. As a result, they can serve as carriers to allow an effective encapsulation of doxorubicin (DOX) for drug delivery. Furthermore, these hydrogels exhibit excellent biocompatibility and degradability in vitro and in vivo. The sustained release of DOX from the hydrogels effectively suppresses tumor growth in animal models without causing significant systemic toxicity, suggesting their potential application in anti-tumor therapies.

Nanoparticle-functionalized acrylic bone cement for local therapeutic delivery to spine metastases

Aim: Polymethylmethacrylate bone cement is often used to reconstruct critical-sized defects generated by the surgical resection of spinal metastases. Residual tumor cells after a resection can drive recurrence and destabilization. Doxorubicin (DOX) is a common chemotherapeutic drug with unwanted side-effects when administered systemically. Mesoporous silica nanoparticles (NPs) are gaining attention for targeted drug delivery to bypass the negative side effects associated with systemic drug administration. An NP-functionalized cement was developed for the local release of DOX and its ability to suppress cancer cells was tested. Methods: DOX was loaded onto NPs which were then mixed into the cement. Static contact angles were measured. Drug release profiles were obtained over a period of 4 weeks. Cement constructs were incubated with two-dimensional (2D) cultures of human bone-marrow derived mesenchymal stem cells and human osteoblasts, as well as 2D and three-dimensional (3D) cultures of breast and prostate cancer cell lines. Cell metabolic activity and viability were evaluated. Cell migration and spheroid growth of cancer cell lines were assessed in collagen-coated spheroid cultures. Results: NPs were homogenously dispersed and did not alter the mechanical strength nor the wettability of the cement. A sustained DOX release profile was achieved with the addition of NPs to the bone cement. The release profile of DOX from NP cement may be modified by varying the amount of the drug loaded onto the NPs and the proportion of NPs in the cement. Cancer cells treated with the cement constructs showed a dose- and time-dependent inhibition, with minimal toxicity against healthy cells. Cancer cell migration and spheroid growth were impaired in 3D culture. Conclusions: NPs were shown to be essential for sustained DOX release from bone cement. DOX-loaded NP cement can inhibit cancer cells and impair their migration, with strong potential for in vivo translation studies.

Core-shell nanomedicine based on multifunctional tetrahedral DNA nanostructures for synergistic enhancement of tumor chemodynamic/chemo-immunotherapy

Immune checkpoint blockade therapy has made great strides in cancer treatment, but conventional immune checkpoint blockade antibodies often lead to overactivation of the immune system and severe immune-related adverse effects. Herein, we report the design of a nanomedicine (denoted as CPD@M−TDN) based on multifunctional tetrahedral DNA nanostructures (M−TDN). In this system, a bimetallic metal–organic framework (Cu/ZIF-8) is synthesized as the core; doxorubicin-loaded polydopamine acts as a shell to reduce the immunogenicity of the nanomaterials in peripheral blood. Finally, the CpG oligodeoxynucleotides and PD-L1 aptamer-based M−TDN are coupled to the core–shell structure nanomedicine through the biotin-avidin-system. Under the acidic tumor microenvironment, the decomposition of Cu/ZIF-8 and the release of copper ions and doxorubicin can lead to immunogenic death of tumor cells through chemodynamic/chemotherapy. Furthermore, the M−TDN has the dual effects of weakening the immunosuppressive microenvironment with PD-L1 aptamer and promoting dendritic cell activation with the immunostimulant CpG. Overall, the developed CPD@M−TDN can effectively enhance the response rate to immunotherapy and has excellent potential in the field of integrated tumor treatment.

Multifunctional rare earth oxide/MBG composite microspheres as a carrier for bone tumor treatment

With the development of advanced composites, biomaterials have brought the field of tissue engineering and regeneration into a new era. Among them, composites of inorganic nonmetallic materials and rare earth oxides have unique structures and biochemical properties and have attracted widespread interest. In this work, rare earth oxides (CeO2)/inorganic nonmetallic materials (mesoporous bioactive glass, MBG) composite microspheres (CeO2/MBGs) were synthesized by a sol-gel method, and the in vitro biological effect of CeO2/MBGs was systematically studied. The filling of CeO2/MBGs in irregular bone tumor defects not only promoted osteogenic mineralization in MG63 cells but also had significant antibacterial effects on E. coli and S. aureus. CeO2 enters the MBG network as a network modifier, while doxorubicin (DOX) is adsorbed into the mesoporous structure through electrostatic interactions, which endows CeO2/MBGs with excellent bioactivity and controlled DOX release behavior. Moreover, the results of in vitro experiments showed that the proper addition of rare earth oxides had no toxic effect on normal cells, and the combination of rare earth oxides with antitumor drugs could slow the release of DOX through the use of an intelligent response design system, thus inducing the apoptosis of MG63 cells. This work suggested that combination chemotherapy and the design of a rare earth oxide/MBG composite microspheres may be potential therapeutic approaches for the postoperative repair of bone tumor defects. The construction of this multifunctional rare earth oxide/inorganic biocomposite provides a way to apply the material to bone tissue.

Preparation of Liposome Gel by Calcium Cross-Linking Induces the Long-Term Release of DOX to Improve the Antitumor Effect.

Doxorubicin (DOX) is one of the most commonly used anticancer drugs; however, its clinical application is greatly limited due to its toxicity and chemotherapy resistance. The delivery of DOX by liposomes (Lipos) can improve the blood circulation time in vivo and reduce toxic side effects, but the drug's accumulation in the tumor is often insufficient for effective treatment. In this study, we present a calcium cross-linked liposome gel for the encapsulation of DOX, demonstrating its superior long-term release capabilities compared to conventional Lipos. By leveraging this enhanced long-term release, we can enhance drug accumulation within tumors, ultimately leading to improved antitumor efficacy. Lipos were prepared using the thin-film dispersion method in this study. We utilized the ion-responsiveness of glutathione-gelatin (GSH-GG) to form the gel outside the Lipos and named the nanoparticles coated with GSH-GG on the outside of Lipos as Lipos@GSH-GG. The average size of Lipos@GSH-GG was around 342.9 nm, with a negative charge of -25.6 mV. The in vitro experiments revealed that Lipos@GSH-GG exhibited excellent biocompatibility and slower drug release compared to conventional Lipos. Further analysis of cellular uptake and cytotoxicity demonstrated that Lipos@GSH-GG loading DOX (DOX&Lipos@GSH-GG) exhibited superior long-term release effects and lower toxic side effects compared to Lipos loading DOX (DOX&Lipos). Additionally, the findings regarding the long-term release effect in vivo and the tumor accumulation within tumor-bearing mice of Lipos@GSH-GG suggested that, compared to Lipos, it demonstrated superior long-term release capabilities and achieved greater drug accumulation within tumors. In vivo antitumor efficacy experiments showed that DOX&Lipos@GSH-GG demonstrated superior antitumor efficacy to DOX&Lipos. Our study highlights Lipos@GSH-GG as a promising nanocarrier with the potential to enhance efficacy and safety by means of long-term release effects and may offer an alternative approach for effective antitumor therapy in the future.

Intelligent Biogenic Missile for Two-Photon Fluorescence Imaging-Guided Combined Photodynamic Therapy and Chemotherapy in Tumors.

Photodynamic therapy (PDT) is a significant noninvasive therapeutic modality, but it is often limited in its application due to the restricted tissue penetration depth caused by the wavelength limitations of the light source. Two-photon (TP) fluorescence techniques are capable of having an excitation wavelength in the NIR region by absorbing two NIR photons simultaneously, which offers the potential to achieve higher spatial resolution for deep tissue imaging. Thus, the adoption of TP fluorescence techniques affords several discernible benefits for photodynamic therapy. Organic TP dyes possess a high fluorescence quantum yield. However, the biocompatibility of organic TP dyes is poor, and the method of coating organic TP dyes with silica can effectively overcome the limitations. Herein, based on the TP silica nanoparticles, a functionalized intelligent biogenic missile TP-SiNPs-G4(TMPyP4)-dsDNA(DOX)-Aptamer (TGTDDA) was developed for effective TP bioimaging and synergistic targeted photodynamic therapy and chemotherapy in tumors. First, the Sgc8 aptamer was used to target the PTK7 receptor on the surface of tumor cells. Under two-photon light irradiation, the intelligent biogenic missile can be activated for TP fluorescence imaging to identify tumor cells and the photosensitizer assembled on the nanoparticle surface can be activated for photodynamic therapy. Additionally, this intelligent biogenic missile enables the controlled release of doxorubicin (DOX). The innovative strategy substantially enhances the targeted therapeutic effectiveness of cancer cells. The intelligent biogenic missile provides an effective method for the early detection and treatment of tumors, which has a good application prospect in the real-time high-sensitivity diagnosis and treatment of tumors.

Reactive oxygen species-sensitive chondroitin sulfate A-cholesteryl hemisuccinate micelles for targeted doxorubicin delivery in tumor therapy

The efficient drug release triggered by the tumor microenvironment is challenging in the development of stimuli-sensitive nanomedicine. In this study, we developed novel polymeric micelles sensitive to reactive oxygen species (ROS) for targeted delivery of doxorubicin (DOX) in tumor therapy. Hydrophilic chondroitin sulfate A (CSA) was conjugated with cholesteryl hemisuccinate (CHS) via a ROS-cleavable thioketal (TK) bond. The resulting CSA-TK-CHS could form self-assembled micelles, and DOX-loaded CSA-TK-CHS (CSA-TK-CHS/DOX) micelles displayed a nearly spherical shape with an average hydrodynamic diameter of 324 nm. The bioresponsive DOX release of CSA-TK-CHS/DOX micelles was evaluated in an H2O2-containing phosphate buffer solution (PBS). CSA-TK-CHS/DOX micelles showed higher cellular uptake than free DOX in 4T1 cells by confocal laser scanning microscopy (CLSM) observation. And CSA-TK-CHS/DOX improved DOX cytotoxicity against CD44-overexpressed 4T1 and CT26 tumor cells. Notably, CSA-TK-CHS/DOX micelles displayed significantly stronger potency (P < 0.01) in antitumor activity than DOX·HCl in orthotropic 4T1-bearing Balb/c mice. Overall, these findings indicate that amphiphilic CSA-TK-CHS micelles are a promising targeted and intelligent drug carrier for tumor therapy.

In vitro evaluation of doxorubicin release from diopside particles on MG-63 and HF spheroids as a 3D model of tumor and healthy tissues

Local drug delivery systems based on bioceramics ensure safe and effective treatment of bone defects and anticancer therapy. A promising drug delivery scaffold material for bone treatment applications is diopside (CaMgSi2O6) which is bioactive, degradable, and possesses drug-release ability. Currently, in vitro assessment of drug release from biomaterials is performed mostly on a 2D cell monolayer. However, to interpret and integrate biochemical signals, cells need a 3D microenvironment that provides cell-cell and cell-extracellular matrix interactions. In this regard, 3D cell models are gaining popularity. In this work, we proposed the protocol for evaluation of the effect of doxorubicin released from diopside on MG-63 cells and primary human fibroblasts in 3D culture conditions. Tissue spheroids with similar diameters were incubated with doxorubicin-loaded diopside for 72 h, the amount of diopside was calculated in accordance with the required doxorubicin concentration. We demonstrated that doxorubicin is gradually released from diopside and exhibits an activity similar to that of the pure drug at the same total concentration. It is important to note that doxorubicin was more potent on MG-63 spheroids compared to HF spheroids, which confirmed the reliability of spheroids as 3D models of tumor and healthy tissues.

Coiled-Coil Protein Hydrogels Engineered with Minimized Fiber Diameters for Sustained Release of Doxorubicin in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) lacks expressed protein targets, making therapy development challenging. Hydrogels offer a promising new route in this regard by improving the chemotherapeutic efficacy through increased solubility and sustained release. Moreover, subcutaneous hydrogel administration reduces patient burden by requiring less therapy and shorter treatment times. We recently established the design principles for the supramolecular assembly of single-domain coiled-coils into hydrogels. Using a modified computational design algorithm, we designed Q8, a hydrogel with rapid assembly for faster therapeutic hydrogel preparation. Q8 encapsulates and releases doxorubicin (Dox), enabling localized sustained release via subcutaneous injection. Remarkably, a single subcutaneous injection of Dox-laden Q8 (Q8•Dox) significantly suppresses tumors within just 1 week. This work showcases the bottom-up engineering of a fully protein-based drug delivery vehicle for improved TBNC treatment via noninvasive localized therapy.

Osteosarcoma cell death induced by innovative scaffolds doped with chemotherapeutics.

Osteosarcoma (OS) cancer treatments include systemic chemotherapy and surgical resection. In the last years, novel treatment approaches have been proposed, which employ a drug-delivery system to prevent offside effects and improves treatment efficacy. Locally delivering anticancer compounds improves on high local concentrations with more efficient tumour-killing effect, reduced drugs resistance and confined systemic effects. Here, the synthesis of injectable strontium-doped calcium phosphate (SrCPC) scaffold was proposed as drug delivery system to combine bone tissue regeneration and anticancer treatment by controlled release of methotrexate (MTX) and doxorubicin (DOX), coded as SrCPC-MTX and SrCPC-DOX, respectively. The drug-loaded cements were tested in an in vitro model of human OS cell line SAOS-2, engineered OS cell line (SAOS-2-eGFP) and U2-OS. The ability of doped scaffolds to induce OS cell death and apoptosis was assessed analysing cell proliferation and Caspase-3/7 activities, respectively. To determine if OS cells grown on doped-scaffolds change their migratory ability and invasiveness, a wound-healing assay was performed. In addition, the osteogenic potential of SrCPC material was evaluated using human adipose derived-mesenchymal stem cells. Osteogenic markers such as (i) the mineral matrix deposition was analysed by alizarin red staining; (ii) the osteocalcin (OCN) protein expression was investigated by enzyme-linked immunosorbent assay test, and (iii) the osteogenic process was studied by real-time polymerase chain reaction array. The delivery system induced cell-killing cytotoxic effects and apoptosis in OS cell lines up to Day 7. SrCPC demonstrates a good cytocompatibility and it induced upregulation of osteogenic genes involved in the skeletal development pathway, together with OCN protein expression and mineral matrix deposition. The proposed approach, based on the local, sustained release of anticancer drugs from nanostructured biomimetic drug-loaded cements is promising for future therapies aiming to combine bone regeneration and anticancer local therapy.

Structure, Self-Assembly, and Phase Behavior of Neuroactive N-Acyl GABAs: Doxorubicin Encapsulation in NPGABA/DPPC Liposomes and Release Studies.

N-Acylated amino acids and neurotransmitters in mammals exert significant biological effects on the nervous system, immune responses, and vasculature. N-Acyl derivatives of γ-aminobutyric acid (N-acyl GABA), which belong to both classes mentioned above, are prominent among them. In this work, a homologous series of N-acyl GABAs bearing saturated N-acyl chains (C8-C18) have been synthesized and characterized with respect to self-assembly, thermotropic phase behavior, and supramolecular organization. Differential scanning calorimetric studies revealed that the transition enthalpies and entropies of N-acyl GABAs are linearly dependent on the acyl chain length. The crystal structure of N-tridecanoyl GABA showed that the molecules are packed in bilayers with the acyl chains aligned parallel to the bilayer normal and that the carboxyl groups from opposite layers associate to form dimeric structures involving strong O-H···O hydrogen bonds. In addition, N-H···O and C-H···O hydrogen bonds between amide moieties of adjacent molecules within each layer stabilize the molecular packing. Powder X-ray diffraction studies showed odd-even alternation in the d spacings, suggesting that the odd chain and even chain compounds pack differently. Equimolar mixtures of N-palmitoyl GABA and dipalmitoylphosphatidylcholine (DPPC) were found to form stable unilamellar vesicles with diameters of ∼300-340 nm, which could encapsulate doxorubicin, an anticancer drug, with higher efficiency and better release characteristics than DPPC liposomes at physiologically relevant pH. These liposomes exhibit faster release of doxorubicin at acidic pH (<7.0), indicating their potential utility as drug carriers in cancer chemotherapy.

Efficient surface modification of silica-alginate nanocarrier as smart drug release platform

A hybrid nanocarrier based on silica-alginate modified by gelatin-folic acid was designed as a pH-sensitive drug delivery system and investigated in the terms of in terms of the amount of doxorubicin loading and release behavior in two different mediums with pH 7.4 and 5.6. The loading content and entrapment efficiency were measured at about 21% and 67%, respectively. The results showed a rapid release of the doxorubicin from the unmodified carrier at initial times (first 24 h). While the use of gelatin-folate modification led to the improvement of the release behavior. Here, the amount of drug released from the silica-alginate carrier after 72 h in a neutral and acidic environment was measured as 82% and 73%, respectively. While using gelatin modification, the amount of released drug decreased to 71% and 63%. These results show that the prepared carrier is sensitive to pH. Furthermore, the cross-linking effect of the gelatin modifier layer on the release pattern was investigated and results indicated the improvement of the release pattern in both acidic and natural media. The findings of this research show the appropriate performance of carriers designed for drug delivery.

Tumor-targeted and stimulus-responsive polymeric prodrug nanoparticles to enhance the anticancer therapeutic efficacy of doxorubicin

Polymeric prodrug nanoparticles have gained increasing attention in the field of anticancer drug delivery because of their dual functions as a drug carrier and a therapeutic agent. Doxorubicin (DOX) is a highly effective chemotherapeutic agent for various cancers but causes cardiotoxicity. In this work, we developed polymeric prodrug (pHU) nanoparticles that serve as both a drug carrier of DOX and a therapeutic agent. The composition of pHU includes antiangiogenic hydroxybenzyl alcohol (HBA) and ursodeoxycholic acid (UDCA), covalently incorporated through hydrogen peroxide (H2O2)-responsive peroxalate. To enhance cancer cell specificity, pHU nanoparticles were surface decorated with taurodeoxycholic acid (TUDCA) to facilitate p-selectin-mediated cancer targeting. TUDCA-coated and DOX-loaded pHU nanoparticles (t-pHUDs) exhibited controlled release of DOX triggered by H2O2, characteristic of the tumor microenvironment. t-pHUDs also effectively suppressed cancer cell migration and vascular endothelial growth factor (VEGF) expression in response to H2O2. In animal studies, t-pHUDs exhibited highly potent anticancer activity. Notably, t-pHUDs, with their ability to accumulate preferentially in tumors due to the p-selectin targeting, surpassed the therapeutic efficacy of equivalent DOX and pHU nanoparticles alone. What is more, t-pHUDs significantly suppressed VEGF expression in tumors and mitigated hepato- and cardiotoxicity of DOX. Given their cancer targeting ability, enhanced therapeutic efficacy and minimized off-target toxicity, t-pHUDs present an innovative and targeted approach with great translational potential as an anticancer therapeutic agent.

PH-responsive self-assembling peptides potentiate therapeutic efficacy via prolonged drug retention and immunomodulation

Insufficient drug accumulation at tumor sites is one of the key factors leading to treatment failure in breast cancer (BC), and developing a chemotherapeutic drug delivery system that can improve the immune microenvironment to expand the benefits of immunochemotherapy for BC remains a challenge. To increase the efficacy of BC treatment by extending drug retention at the tumor site, we developed a pH-responsive peptide modified with the PHSCN peptide sequence (Pep1) that self-assembles to form spherical DM/Pep1 nanoparticles after encapsulating doxorubicin (DOX) and metformin (MET). In the acidic tumor microenvironment, spherical nanocarriers transform into aggregates with a high aspect ratio, facilitating DOX and MET release for combined chemotherapy and immunomodulation. In cellular experiments, this construct provided prolonged drug retention in BC cells. In a subcutaneous tumor mouse model, the DM/Pep1 nanoparticles exhibited a superior tumor inhibition effect compared to that of free DOX/MET. The DM/Pep1 nanocomplex upregulated CD4, induced calreticulin (CRT) exposure, downregulated PD-L1, and enhanced the MET-mediated antitumor immune response. The use of this pH-responsive peptide nanocarrier system with morphological transformation offers a promising strategy for BC therapy.

Tumor microenvironment responsive multifunctional smart living materials based on engineered bacteria for inducing macrophage polarization to enhance tumor immunotherapy

The utilization of bacteria as a drug delivery system represents a promising strategy for tumor therapy, owing to their inherent ability to selectively colonize and induce apoptosis of tumor cells at the solid tumor. However, the occurrence of dose-dependent toxicity has led to the failure of clinical trials. Unfortunately, the implementation of a singular bacterial treatment strategy for tumor therapy is inherently limited. In this study, we developed a living drug delivery material named DOX@TA@ECN (D@T@E) by utilizing Fe3+ and tannin acid (TA) as a cross-linking network to encapsulate doxorubicin (DOX) and form a protective coating on the surface of Escherichia coli Nissle 1917 (ECN). In an acidic tumor microenvironment, D@T@E disintegrated the coating to release DOX through the highly expressed H2O2. To enhance biosafety, the D@T@E was equipped with a hypoxic lytic circuit (Pvhb-Lysis) to regulate the number of ECN in vivo (D@T@E-PL). The hypoxic promotor of Vitreoscilla hemoglobin protein (Pvhb) were activied to induce expression of lysis protein (PhiX174E) in the tumor hypoxic microenvironment (3 %), resulting in ECN lysis and subsequent elimination by the immune system. Additionally, D@T@E-PL pass lysis to release relevant antigens (DNA and flagellin). This antigen promotes the polarization of M2-type tumor-promoting macrophages towards M1-type anti-tumor macrophages at the tumor microenvironment by activating Toll-like receptor 4 (TLR4), eliciting immune-mediated anti-tumor responses. The in vivo findings demonstrated that D@T@E-PL intelligent material demonstrated enhanced biosecurity through the lytic circuit and effectively suppressed tumor growth, thereby achieving a dual therapeutic approach combining chemotherapy and immunotherapy for tumor inhibition.

Multilayer pH-responsive hollow mesoporous silica nanoparticles with charge reversal for drug delivery and real-time monitoring by fluorescence

Drug delivery systems (DDSs) with charge reversal could simultaneously achieve long circulation time and enhanced cellular internalization efficiency. Here, hollow mesoporous silica nanoparticles (HMSNs) were used as the basic stuff for encapsulating doxorubicin (DOX), positive-charged chitosan (CS) was grafted on the surface of HMSNs, and negatively charged carboxyl-rich carbon dots (CDs) were coated on the outer layer of CS through non-covalent bonds. The new drug delivery vehicles with 56.6 % drug-loading content were prepared, named as CDs-CS/HMSNs@DOX. Tumor environment with a slightly acidic state could trigger the disruption of the non-covalent bonds, followed by the detachment of CDs, making the negatively charged CDs-CS/HMSNs@DOX change into positively charged CS/HMSNs@DOX. CS swelling reaction also happened in slightly acidic conditions. Both the CS swelling and the detachment of CDs resulted in the exposure of mesopore and drug release. Fluorescence recovery of detached CDs could be used to monitor the release of DOX in real-time. The multilayer pH-responsive nano carries with charge reversal and real-time monitoring demonstrated broad application prospects.

Zwitterionic functionalization of polysaccharide gum by graft copolymerization to develop 3-D network materials for anticancer drug delivery applications

Herein, functionalization of polysaccharide gum has been carried out to develop network copolymeric materials for use in sustained anticancer drug delivery. Grafting reaction of poly[2-(methacryloyloxy)ethyl] dimethyl-(3-sulfopropyl)ammonium hydroxide (MEDSAH) onto sterculia gum has been done in the presence of crosslinker. Copolymeric materials were characterized by scanning electron micrographs (SEMs), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), 13C-nuclear magnetic resonance (NMR), and thermogravimetric analysis (TGA). SEM, AFM and XRD displayed heterogeneous morphology with a rough surfaces of amorphous copolymeric materials. Peaks at 173.822 ppm (carbonyl carbon) and at 60.653 ppm (methylene carbon attached to a quaternary ammonium group) confirmed the addition of poly(MEDSAH) during the grafting reaction. Mesh size in network hydrogel was found between 14.54 nm to 36.32 nm. Sustained release of doxorubicin was found with non-Fickian diffusion and was best demonstrated by the kinetic model Hixson Crowell. The biocompatibility of material was revealed in a haemolytic index (1.74 ± 0.26%) less than two percent during the copolymer-blood interaction. The material exhibited antioxidant and mucoadhesion properties. Free radical scavenging ability of copolymers was 49.41 ± 0.97% in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay of the antioxidant test. These properties of copolymeric hydrogels demonstrated their suitability for use in sustained drug delivery systems for cancer chemotherapy.

Porphyrin-based covalent organic frameworks as doxorubicin delivery system for chemo-photodynamic synergistic therapy of tumors

Photodynamic therapy (PDT) is a non-invasive treatment method that has garnered significant attention in recent years. Nanoparticle-based drug delivery systems can achieve targeted drug release, thereby significantly reducing side effects and enhancing therapeutic efficacy. In this study, a covalent organic framework (COF) with an approximately spherical structure connected by azo bonds was synthesized. The synthesized COF was utilized as a hypoxia-responsive carrier for doxorubicin (DOX) drug delivery and was modified with hyaluronic acid (HA). DOX@COF@HA exhibited a reactive release under hypoxic conditions. Under normal oxygen conditions, the release of DOX was 16.9 %, increasing to 60.2 % with the addition of sodium hydrosulfite. In vitro experiments revealed that the group combining photodynamic therapy with chemotherapy exhibited the lowest survival rates for 4T1 and MHCC97-L cells. In vivo experiments further validated the effectiveness of combination therapy, resulting in a tumor volume of only 33 mm3 after treatment, with no significant change in mouse weight during the treatment period. DOX@COF@HA nanoplatforms exhibit substantial potential in tumor treatment.