Controlled Release Of Doxorubicin Research Articles

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.

Ultrasound triggered local sequential reactive oxygen species and nitric oxide release for enhanced cerasomal drug delivery

Liposomal drug delivery for tumor therapy was still suffered from low stability, limited delivering efficiency and poor tumor penetration, greatly compromising the therapeutic efficacy. Herein, a stable and ultrasound triggered cerasomal drug delivery system was developed by loading doxorubicin (DOX) into stable liposomal cerasome, which was self-assembled from cerasome-forming lipid (CFL), sonosensitizer of porphyrin lipid (PL), nitric oxide (NO) donor of DSPE-PEG2000-SNO and unsaturated phospholipids DOPC, resulting in DOX@PC-SNO with stable siloxane network and S-nitrosothiol on surface, sonosensitizer in lipid bilayer and DOX in the core. DOX@PC-SNO can prevent drug leakage during blood circulation and efficiently accumulate at the tumor site at 24 h post-injection, while controllably generate reactive oxygen species (ROS) upon local ultrasound irradiation on tumor, which can not only use for SDT, but also operate as a switch for on-demand controlled release of internal DOX and external NO, resulting in specific delivery and high penetration of chemotherapeutic drug into the deep tumor, thus greatly improved antitumor efficacy without observed side effects.

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.

A Mesoporous Magnetic Fe3O4/BioMOF-13 with a Core/Shell Nanostructure for Targeted Delivery of Doxorubicin to Breast Cancer Cells.

In the current project, magnetic Bio-MOF-13 was used as an efficient carrier for the targeted delivery and controlled release of doxorubicin (DOX) to MDA-MB-231 cells. Magnetic Bio-MOF-13 was prepared by two strategies and compared to determine the optimal state of the structure. In the first path, Bio-MOF-13 was grown in situ on the surface of Fe3O4 nanoparticles (core/shell structure), while in the second method, the two presynthesized materials were mixed together (surface composite). Core/shell structure, among prepared nanocomposites, was chosen for biological evaluation due to its favorable structural features like a high accessible surface area and pore volume. Also, it is highly advantageous for drug release due to its ability to selectively release DOX in the acidic pH of breast cancer cells, while preventing any premature release in the neutral pH of the blood. Drug release from the carrier structure is precisely controlled not only by pH but also by an external magnetic field, guaranteeing accurate drug delivery at the intended location. Confocal microscopy and flow cytometry assay clearly confirms the increase in drug concentration in the MDA-MB-231 cell line after external magnet applying. This point, along with the low toxicity of the carrier components, makes it a suitable candidate for injectable medicine. According to MTT results, the percentage of viable MDA-MB-231 cells after treatment with 10 μL of DOX@Fe3O4/Bio-MOF-13 core/shell composite in different concentrations, in the presence and absence of magnetic field is 0.87 ± 0.25 and 2.07 ± 0.15, respectively. As a result, the DOX@Fe3O4/Bio-MOF-13 core/shell composite was performed and approved for targeted drug delivery and magnetic field-assisted controlled release of DOX to the MDA-MB-231 cell line.

Subtractive Nanopore Engineered MXene Photonic Nanomedicine with Enhanced Capability of Photothermia and Drug Delivery for Synergistic Treatment of Osteosarcoma.

Two-dimensional (2D) nanomaterials as drug carriers and photosensitizers have emerged as a promising antitumor strategy. However, our understanding of 2D antitumor nanomaterials is limited to intrinsic properties or additive modification of different materials. Subtractive structural engineering of 2D nanomaterials for better antitumor efficacy is largely overlooked. Here, subtractively engineered 2D MXenes with uniformly distributed nanopores are synthesized. The nanoporous defects endowed MXene with enhanced surface plasmon resonance effect for better optical absorbance performance and strong exciton-phonon coupling for higher photothermal conversion efficiency. In addition, porous structure improves the binding ability between drug and unsaturated bonds, thus promoting drug-loading capacity and reducing uncontrolled drug release. Furthermore, the porous structure provides adhesion sites for filopodia, thereby promoting the cellular internalization of the drug. Clinically, osteosarcoma is the most common bone malignancy routinely treated with doxorubicin-based chemotherapy. There have been no significant treatment advances in the past decade. As a proof-of-concept, nanoporous MXene loaded with doxorubicin is developed for treating human osteosarcoma cells. The porous MXene platform results in a higher amount of doxorubicin-loading, faster near-infrared (NIR)-controlled doxorubicin release, higher photothermal efficacy under NIR irradiation, and increased cell adhesion and internalization. This facile method pioneers a new paradigm for enhancing 2D material functions and is attractive for tumor treatment.

A fluorescent system based on graphene quantum dots-capped magnetic hydroxyapatite-MIL-100 metal-organic frameworks for pH-sensitive and controlled release of DOX

Since metal-organic frameworks (MOFs) have shown great potential as emerging candidates in biomedical applications, it is worthwhile to construct an MOF-based drug delivery system. Hence, in this work, magnetic hydroxyapatite-MIL-100 metal-organic frameworks (SiO2@Fe3O4-HA-MIL-100) with antioxidant properties were synthesized as a novel drug delivery system through in-situ self-assembly of MIL-100 MOFs around pre-synthesized magnetic hydroxyapatite nanoparticles. Then, SiO2@Fe3O4-HA-MIL-100 nanocomposites were capped with fluorescent graphene quantum dots (SiO2@Fe3O4-HA-MIL-100-GQDs) for loading and delivering of doxorubicin (DOX). The SiO2@Fe3O4-HA-MIL-100, GQDs, and SiO2@Fe3O4-HA-MIL-100-GQDs encapsulation efficiency was 80.2, 42.2, and 95.8 %, respectively. The in vitro DOX release amount after 72 h from SiO2@Fe3O4-HA-MIL-100, GQDs, and SiO2@Fe3O4-HA-MIL-100-GQDs at pH 5 was 75.8 %, 86.2 %, and 67.2 %, while at pH 7.4 was 37.3 %, 50.1 %, and 29 %, respectively. These results confirmed a pH-responsive controlled release of DOX from nanocomposites. The release mechanism of DOX from the prepared nanocomposites was also well fitted to the Korsmeyer-Peppas kinetic, Fickian diffusion, and diffusion-controlled release. In addition, the MTT assays of nanocomposites against MCF-7 breast cancer cell lines clearly illustrated that the prepared nanocomposites had no significant cytotoxicity, while DOX-loaded nanocomposites had notable toxicity to MCF-7 cells. The IC50 values of DOX, SiO2@Fe3O4-HA-MIL-100-DOX, GQDs-DOX, and SiO2@Fe3O4-HA-MIL-100-GQDs-DOX against MCF-7 cells calculated at about 4.2 μg/mL, 1.8 μg/mL, 3 μg/mL, and 1.2 μg/mL, respectively. The DPPH test results also showed that the nanocomposites have excellent antioxidant activity. In addition, the in vitro hemolysis results displayed neglectable hemolysis activity (lower than 5 %) of SiO2@Fe3O4-HA-MIL-100-GQDs even at a high dose. Therefore, these new drug delivery systems can be used safely as potential drug carriers in targeted cancer therapy.

Floating poly(lactic-co-glycolic acid)-based controlled-release drug delivery system for intravesical instillation

To investigate the floating, structural, and controlled-release characteristics of a floating poly(lactic-co-glycolic acid) (PLGA)-based controlled-release drug delivery system, and determine the feasibility of this drug delivery system for intravesical instillation. PLGA was dissolved in dimethylacetamide, then mixed with IR780 and doxorubicin (DOX) to prepare a drug delivery system capable of solidification and flotation on water at room temperature. Preparations of PLGA, PLGA+IR780, PLGA+DOX, and PLGA+IR780+DOX were formulated. Their floating characteristics in vivo and in vitro were investigated, along with their structural and controlled-release characteristics. Preparations of saline, DOX, and PLGA+IR780+DOX were also formulated; the content of DOX in bladder tissue delivered by each preparation was determined by fluorescence microscopy. PLGA exhibited stable flotation in vivo and in vitro. A honeycomb structure was observed by scanning electron microscopy. When irradiated with a near-infrared laser, IR780 generated heat that vitrified PLGA, allowing controlled release of DOX from the drug delivery system. The PLGA+IR780+DOX preparation achieved the highest content of DOX in bladder tissue. Our floating PLGA-based controlled-release drug delivery system exhibited a honeycomb stabilized structure and achieved controlled release when irradiated by a near-infrared laser, making it an ideal drug delivery system for intravesical instillation.

Facile synthesis of copolymerized cellulose grafted hydrogel doped calcium oxide nanocomposites with improved antioxidant activity for anti-arthritic and controlled release of doxorubicin for anti-cancer evaluation

The combination treatment is considered an approach to attaining synergistic impact while minimizing applied dosage. Hydrogels are analogous to the tissue environment attributed to hydrophilic and porous structure. Despite extensive study in biological and biotechnological domains, their restricted mechanical strength and limited functionalities impede their potential uses. Emerging strategies are centred on research and developing nanocomposite hydrogels to combat these issues. Herein, we prepared copolymerized hydrogel by grafting poly-acrylic acid P(AA) onto cellulose nanocrystals (CNC) and adding CNC-g-PAA as dopant (2 and 4 wt%) in calcium oxide (CaO) nanoparticles to generate an effective hydrogel doped nanocomposite (NCH) (CNC-g-PAA/CaO) for biomedical applications such as anti-arthritic, anti-cancer, and antibacterial investigations alongside their comprehensive characterization. CNC-g-PAA/CaO (4 %), compared to other samples, had a substantially higher antioxidant potential (72.21 %). Doxorubicin, a potential chemotherapeutic drug, was then effectively loaded into NCH (99 %) via electrostatic interaction, and pH-triggered based release was found to be >57.9 % in 24 h. Furthermore, molecular docking investigation against targeted protein Cyclin-dependent kinase 2 and in vitro cytotoxicity study verified the improved antitumor effectiveness of CNC-g-PAA and CNC-g-PAA/CaO. These outcomes indicated that hydrogels might serve as potential delivery vehicles for innovative multifunctional biomedical applications.

Fabrication of biocompatible magnetic maltose/MIL-88 metal–organic frameworks decorated with folic acid-chitosan for targeted and pH-responsive controlled release of doxorubicin

Recently, metal–organic frameworks (MOFs) have attracted tremendous attention as promising porous drug delivery systems for cancer treatment. In this work, for the first time, a novel magnetic maltose disaccharide molecule modified with MIL-88 metal–organic framework (Fe3O4@C@MIL-88) was prepared, and then this targeted system was used for the delivery of the doxorubicin (DOX) drug. Eventually, Fe3O4@C@MIL-88-DOX were successfully decorated with folic acid conjugated chitosan (Fe3O4@C@MIL-88-DOX-FC) as a new targeted and controlled release drug system for treatment of MCF-7 breast cancer. The encapsulation efficiency of the DOX in the Fe3O4@C@MIL-88 was obtained at ∼83.6%. The in vitro drug release profiles showed a pH-responsive controlled release of DOX in acidic pH confirming the performance of the systems in the cancerous environment. The DOX release mechanism from systems at pH 5 also showed that the kinetic data well fitted to the Korsmeyer-Peppas and Fickian diffusion. Furthermore, in vitro cytotoxicity and DAPI staining study clearly illustrated that the synthesized Fe3O4@C@MIL-88 system had low cytotoxicity and good biocompatibility against MCF-7 cancer cells and MCF-10A normal cells. Whereas, Fe3O4@C@MIL-88-DOX and Fe3O4@C@MIL-88-DOX-FC exhibited good antitumor activity as a result of targeted delivery of DOX, which indicated the MCF-7 cell death with apoptotic effects. Based on these findings, the resulting carriers could be used as promising targeted drug delivery systems for cancer therapy.

Polymer/magnetite carriers functionalized by HER2-DARPin: Avoiding lysosomes during internalization and controlled toxicity of doxorubicin by focused ultrasound induced release

Nanomedicine has revolutionized the available treatment options during the last decade, but poor selectivity of targeted drug delivery and release is still poses a challenge. In this study, doxorubicin (DOX) and magnetite nanoparticles were encapsulated by freezing-induced loading, coated with polymeric shell bearing two bi-layers of polyarginine/dextran sulphate and finally modified with HER2-specific DARPin proteins. We demonstrated that the enhanced cellular uptake of these nanocarriers predominantly occurs by SKOV-3 (HER2+) cells, in comparison to CHO (HER2−) cells, together with the controlled DOX release using low intensity focused ultrasound (LIFU). In addition, a good ability of DARPin+ capsules to accumulate in the tumor and the possibility of combination therapy with LIFU were demonstrated. A relatively high sensitivity of the obtained nanocarriers to LIFU and their preferential interactions with mitochondria in cancer cells make these carriers promising candidates for cancer treatment, including novel approaches to overcome drug resistance.

Preparation of a pH-responsive chitosan-montmorillonite-nitrogen-doped carbon quantum dots nanocarrier for attenuating doxorubicin limitations in cancer therapy.

Despite its widespread usage as a chemotherapy drug in cancer treatment, doxorubicin (DOX) has limitations such as short in vivo circulation time, low solubility, and poor permeability. In this regard, a pH‐responsive chitosan (CS)‐ montmorillonite (MMT)‐ nitrogen‐doped carbon quantum dots (NCQDs) nanocomposite was first developed, loaded with DOX, and then incorporated into a double emulsion to further develop the sustained release. The incorporated NCQDs into the CS‐MMT hydrogel exhibited enhanced loading and entrapment efficiencies. The presence of NCQDs nanoparticles in the CS‐MMT hydrogel also resulted in an extended pH‐responsive release of DOX over a period of 96 h compared to that of CS‐MMT‐DOX nanocarriers at pH 5.4. Based on the Korsmeyer‐Peppas model, there was a controlled DOX release at pH 5.4, while no diffusion was observed at pH 7.4, indicating fewer side effects. MTT assay showed that the cytotoxicity of DOX‐loaded CS‐MMT‐NCQDs hydrogel nanocomposite was significantly higher than those of free DOX (p < 0.001) and CS‐MMT‐NCQDs (p < 0.001) on MCF‐7 cells. Flow cytometry results demonstrated that a higher apoptosis induction achieved after incorporating NCQDs nanoparticles into CS‐MMT‐DOX nanocarrier. These findings suggest that the DOX‐loaded nanocomposite is a promising candidate for the targeted treatment of cancer cells.

Formation of biocompatible MgO/cellulose grafted hydrogel for efficient bactericidal and controlled release of doxorubicin

In this study, MgO-doped CNC-g-PAA hydrogel was synthesized by grafting poly (acrylic acid) (PAA) onto cellulose nanocrystals (CNC) and then doped Magnesium oxide (MgO) using pH 7.0 and 12.0 to obtain an efficient nanocomposite hydrogel for antibacterial and anti-cancer activities. The synthesized nanocomposite hydrogels were evaluated by detailed characterization and confirmed the formation of a well-interconnected porous structure. MgO/CNC-g-PAA (pH = 12.0) exhibited improved bactericidal tendencies towards gram-negative and gram-positive bacteria, which was further investigated by in-silico molecular docking analyses and also examined the reactive oxygen species production by photocatalysis and free radical-scavenging assay. After this, Doxorubicin (DOX), a model anticancer drug, was successfully loaded into nanocomposites (∼79 %) by electrostatic interaction and confirmed pH-triggered based release, which was over 53.7 % in 24 h. Finally, in vitro cytotoxicity-based analysis confirmed the improved antitumor efficacy of nanocomposite hydrogels. These findings revealed that MgO/CNC-g-PAA hydrogels might be prospective carriers for controlled drug delivery.

Folate-Targeted PEGylated Magnetoliposomes for Hyperthermia-Mediated Controlled Release of Doxorubicin.

Doxorubicin (DOX) is a chemotherapeutic agent commonly used for the treatment of solid tumors. However, the cardiotoxicity associated with its prolonged use prevents further adherence and therapeutic efficacy. By encapsulating DOX within a PEGylated liposome, Doxil® considerably decreased DOX cardiotoxicity. By using thermally sensitive lysolipids in its bilayer composition, ThermoDox® implemented a heat-induced controlled release of DOX. However, both ThermoDox® and Doxil® rely on their passive retention in tumors, depending on their half-lives in blood. Moreover, ThermoDox® ordinarily depend on invasive radiofrequency-generating metallic probes for local heating. In this study, we prepare, characterize, and evaluate the antitumoral capabilities of DOX-loaded folate-targeted PEGylated magnetoliposomes (DFPML). Unlike ThermoDox®, DOX delivery via DFPML is mediated by the heat released through dynamic hysteresis losses from magnetothermal converting systems composed by MnFe2O4 nanoparticles (NPs) under AC magnetic field excitation—a non-invasive technique designated magnetic hyperthermia (MHT). Moreover, DFPML dismisses the use of thermally sensitive lysolipids, allowing the use of simpler and cheaper alternative lipids. MnFe2O4 NPs and DFPML are fully characterized in terms of their size, morphology, polydispersion, magnetic, and magnetothermal properties. About 50% of the DOX load is released from DFPML after 30 min under MHT conditions. Being folate-targeted, in vitro DFPML antitumoral activity is higher (IC50 ≈ 1 μg/ml) for folate receptor-overexpressing B16F10 murine melanoma cells, compared to MCF7 human breast adenocarcinoma cells (IC50 ≈ 4 μg/ml). Taken together, our results indicate that DFPML are strong candidates for folate-targeted anticancer therapies based on DOX controlled release.

Carbon fibres as potential bone implants with controlled doxorubicin release

This work presents the structural characterisation of carbon fibres obtained from the carbonization of flax tow at 400°C (CFs400°C) and 1000°C (CFs1000°C) and the thermodynamic and kinetic studies of adsorption of Doxorubicin (Dox) on the fibres. The characteristic of carbon fibres and their drug adsorption and removal mechanism were investigated and compared with that of natural flax tow. All fibres were fully characterized by scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), specific surface area analysis and Boehm titration. The results demonstrated the highest adsorption properties of CFs400°C at 323 K (qmax = 275 mg g−1). The kinetic data followed the pseudo-second-order kinetic model more closely, whereas the Dubinin–Radushkevich model suitably described isotherms for all fibres. Calculated parameters revealed that the adsorption process of Dox ions is spontaneous and mainly followed by physisorption and a pore-filling mechanism. The removal efficiency for carbon fibres is low due to the effect of pore-blocking and hydrophobic hydration. However, presented fibres can be treated with a base for further chemical surface modification, increasing the adsorption capacity and controlling the release tendency.

PH-responsive supramolecular nanoparticles based on sulfobutylether7-β-CD/cationic surfactant and its controllable release of doxorubicin

Novel supramolecular nanoparticles were successfully built by sulfobutylether7-β-cyclodextrin and benzyl dodecyl dimethyl ammonium bromide. The assembly and disassembly behavior were determined by UV–Vis, Tyndall effect, dynamic light scattering, transmission electron microscopy, and zeta potential. Upon decreasing pH values, the resulting nanoparticles disassemble. The nanoparticles will be restored to spherical nanoparticles when the pH increases to the initial value. Due to the negative zeta potential, the nanoparticles showed good loading capacity for doxorubicin (DOX). DOX-loaded nanoparticles exhibited pH-responsive drug release behavior and possess higher cytotoxicity than the positive control, cisplatin. Thus, the simple and effective supramolecular nanoparticles with desirable load/release DOX property was constructed as pH-responsive drug delivery system.

PH-sensitive doxorubicin-tocopherol succinate prodrug encapsulated in docosahexaenoic acid-based nanostructured lipid carriers: An effective strategy to improve pharmacokinetics and reduce toxic effects

Side effects often limit the use of doxorubicin (DOX) in cancer treatment. We have recently developed a nanostructured lipid carrier (NLC) formulation for synergistic chemotherapy, encapsulating DOX and the anticancer adjuvants docosahexaenoic acid (DHA) and α-tocopherol succinate (TS). Hydrophobic ion-pairing with TS allowed a high DOX entrapment in the nanocarrier. In this work, we investigated the pharmacokinetics of this formulation after intravenous administration in mice. The first data obtained led us to propose synthesizing covalent DOX-TS conjugates to increase DOX retention in the NLC. We successfully conjugated DOX to TS via an amide or hydrazone bond. In vitro studies in 4T1 tumor cells indicated low cytotoxicity of the amide derivative, while the hydrazone conjugate was effective in killing cancer cells. We encapsulated the hydrazone derivative in a DHA-based nanocarrier (DOX-hyd-TS/NLC), which had reduced particle size and high drug encapsulation efficiency. The pH-sensitive hydrazone bond allowed controlled DOX release from the NLC, with increased drug release at acidic conditions. In vivo studies revealed that DOX-hyd-TS/NLC had a better pharmacokinetic profile than free DOX and attenuated the short-term cardiotoxic effects caused by DOX, such as QT prolongation and impaired left ventricular systolic function. Moreover, this formulation showed excellent therapeutic performance by reducing tumor growth in 4T1 tumor-bearing mice and decreasing DOX-induced toxicity to the heart and liver, demonstrated by hematologic, biochemical, and histologic analyses. These results indicate that DOX-hyd-TS/NLC may be a promising nanocarrier for breast cancer treatment.

A dual functional superparamagnetic system with pH-dependent drug release and hyperthermia potential for chemotherapeutic applications

A biodegradable, dual functional drug delivery system with superparamagnetic property (Ms: 50.1 emu g−1) for magnetic hyperthermia and tumour-specific pH-dependent drug delivery (loading capacity: 58 μg mg−1) has been designed with magnetically modulated nanocellulose. Increased site-specific bioavailability, effective magnetic hyperthermia potential and pH-responsive controlled release of Doxorubicin (Dox) have been accomplished with a single system, and hence, it is proposed as a multimodal therapeutic tool.

Degradable pH-responsive polymer prodrug micelles with aggregation-induced emission for cellular imaging and cancer therapy

Polymeric micelles with simultaneous bioimaging, drug delivery monitoring, and effective delivery of therapeutic agents to target sites have attracted increasing attention in cancer therapy. In this study, a new biodegradable, pH-responsive, aggregation-induced emission (AIE)-active polycarbonate brush-like polymer was developed by combining ring-opening polymerization with click reaction. The anticancer drug, doxorubicin (DOX), was covalently conjugated to the polymer backbone via acid-sensitive Schiff base linkage, resulting in the pH-sensitive controlled release of DOX. The prodrug polymer self-assembled into nanomicelles in an aqueous solution, as confirmed using dynamic light scattering and transmission electron microscopy. Fluorescence imaging results demonstrated that prodrug micelles could be traced owing to the AIE features of micelles. In vitro drug release studies showed that DOX release was faster in acidic conditions (pH 5.0), whereas only a minimal amount of DOX was released in a physiological environment (pH 7.4). In summary, these smart prodrug micelles could be promising candidates for simultaneous intracellular imaging and cancer therapy.

Gold nanorods-encapsulated thermosensitive drug carriers for NIR light-responsive anticancer therapy

Thermoresponsive polymers incorporated with photo-absorbing agents have been widely utilized for controlled drug delivery using light as an external stimulus. However, previously developed thermoresponsive drug carriers have disadvantages such as low biocompatibility and implantation failure. In the present study, gold nanorods (GNRs)-encapsulated poly(N-vinyl caprolactam) (PVCL) (GNR-PVCL) microparticles were synthesized by the stop-flow lithography (SFL) method. The SFL method enabled the fabrication of near-infrared (NIR) light-responsive GNR-PVCL microparticles of uniform size, which can allow localized injection. Doxorubicin (DOX) was encapsulated into GNR-PVCL microparticles to achieve NIR light-responsive anticancer therapy. DOX-loaded GNR-PVCL (DOX-GNR-PVCL) microparticles exhibited NIR light-triggered drug release due to the photothermal effect of GNRs, which increases the local temperature above the volume phase transition temperature of GNR-PVCL microparticles. In addition, DOX-GNR-PVCL exhibited controlled DOX release in response to the periodic irradiation of NIR light. Moreover, we demonstrated the efficient intracellular release of DOX upon NIR light exposure, and thus, NIR light-responsive anticancer activity. This study demonstrates that DOX-GNR-PVCL microparticles have significant potential as implantable drug carriers enabling NIR light-triggered drug release.

Graphene quantum dots based magnetic nanoparticles as a promising delivery system for controlled doxorubicin release

In this study, a nanocarrier was prepared for targeted delivery of doxorubicin (DOX), as a drug model, to cancer cells. To this end, nontoxic Fe3O4 nanoparticles (NPs) were first synthesized by the co-precipitation method. The NPs then underwent surface functionalization by hydrophilic and biocompatible polyethylene glycol (PEG) to improve their stability. The Fe3O4@PEG was eventually decorated by graphene quantum dots (GQDs) for imparting specific optical properties and increase its drug loading capacity. The obtained nanocarriers (Fe3O4@PEG@GQD) exhibited low toxicity, hydrodynamic diameter of 129 nm, and a drug loading content of 27%, along with superior superparamagnetic properties. Also, the morphology of nanocarrier was surveyed by transmission electron microscopy (TEM). The drug release studies indicated a pH-dependent profile where higher release rates were observed at acidic pH (5.0) as compared with the physiological pH (7.4). The anticancer activity of Fe3O4@PEG@GQD-DOX was comparable to free drugs in the case of human breast cancer cells. The introduced nano-drug delivery system can be considered as a promising candidate for the controlled release of DOX. Finally, quantum mechanical computations were employed in a better understanding of drug release mechanism. The results showed a decline in the adsorption energy of the drug on GQDs from −107.1 kJ mol−1 at pH 7 to −66.2 kJ mol−1 at pH 5. Moreover, the HOMO-LUMO calculation and the electrostatic surface potential method were applied to further explore the drug-GQDs interactions.