Release Of Drug Doxorubicin Research Articles

NIR Stimulus-Responsive PdPt Bimetallic Nanoparticles for Drug Delivery and Chemo-Photothermal Therapy.

The combination of chemotherapy and phototherapy has attracted increasing attention for cancer treatment in recent years. In the current study, porous PdPt bimetallic nanoparticles (NPs) were synthesized and used as delivery carriers for the anti-cancer drug doxorubicin (DOX). DOX@PdPt NPs were modified with thiol functionalized hyaluronic acid (HA-SH) to generate DOX@PdPt@HA NPs with an average size of 105.2 ± 6.7 nm. Characterization and in vivo and in vitro assessment of anti-tumor effects of DOX@PdPt@HA NPs were further performed. The prepared DOX@PdPt@HA NPs presented a high photothermal conversion efficiency of 49.1% under the irradiation of a single 808 nm near-infrared (NIR) laser. Moreover, NIR laser irradiation-induced photothermal effect triggered the release of DOX from DOX@PdPt@HA NPs. The combined chemo-photothermal treatment of NIR-irradiated DOX@PdPt@HA NPs exerted a stronger inhibitory effect on cell viability than that of DOX or NIR-irradiated PdPt@HA NPs in mouse mammary carcinoma 4T1 cells in vitro. Further, the in vivo combination therapy, which used NIR-irradiated DOX@PdPt@HA NPs in a mouse tumor model established by subcutaneous inoculation of 4T1 cells, was demonstrated to achieve a remarkable tumor-growth inhibition in comparison with chemotherapy or photothermal therapy alone. Results of immunohistochemical staining for caspase-3 and Ki-67 indicated the increased apoptosis and decreased proliferation of tumor cells contributed to the anti-tumor effect of chemo-photothermal treatment. In addition, DOX@PdPt@HA NPs induced negligible toxicity in vivo. Hence, the developed nanoplatform demonstrates great potential for applications in photothermal therapy, drug delivery and controlled release.

Photo- and pH-Responsive Polycarbonate Block Copolymer Prodrug Nanomicelles for Controlled Release of Doxorubicin.

Photo/pH dual-responsive amphiphilic diblock copolymers with alkyne functionalized pendant o-nitrobenzyl ester group are synthesized using poly(ethylene glycol) as a macroinitiator. The pendant alkynes are functionalized as aldehyde groups by the azide-alkyne Huisgen cycloaddition. The anticancer drug doxorubicin (DOX) molecules are then covalently conjugated through acid-sensitive Schiff-base linkage. The resultant prodrug copolymers self-assemble into nanomicelles in aqueous solution. The prodrug nanomicelles have a well-defined morphology with an average size of 20-40nm. The dual-stimuli are applied individually or simultaneously to study the release behavior of DOX. Under UV light irradiation, nanomicelles are disassembled due to the ONB ester photocleavage. The light-controlled DOX release behavior is demonstrated using fluorescence spectroscopy. Due to the pH-sensitive imine linkage the DOX molecules are released rapidly from the nanomicelles at the acidic pH of 5.0, whereas only minimal amount of DOX molecules is released at the pH of 7.4. The DOX release rate is tunable by applying the dual-stimuli simultaneously. In vitro studies against colon cancer cells demonstrate that the nanomicelles show the efficient cellular uptake and the intracellular DOX release, indicating that the newly designed copolymers with dual-stimuli-response have significant potential applications as a smart nanomedicine against cancer.

Biodegradable Mesoporous Organosilica Nanosheets for Chemotherapy/Mild Thermotherapy of Cancer: Fast Internalization, High Cellular Uptake, and High Drug Loading.

The choice of nanocarriers is crucial to fabricate ideal therapeutic nanoplatform in the treatment of cancer. Considering the advantages brought by the two-dimensional (2D) materials with atomic thickness in drug loading and cellular uptake, herein, novel 2D biodegradable mesoporous organosilica nanosheets (MONSs) are presented, and their application in chemotherapy/mild thermotherapy of cancer is studied by loading chemotherapy drug doxorubicin (DOX) and conjugating ultrasmall CuS nanoparticles. It is found that the loading of DOX in MONSs is as high as 859 μg/mg due to their large surface area and intermediate void structure. The release of DOX from MONSs is intelligently controlled by pH value, glutathione (GSH) concentration, and laser irradiation. Excitingly, in comparison with traditional spherical mesoporous organosilica nanoparticles, as-prepared MONSs not only show more rapid degradation but also exhibit faster internalization and higher cellular uptake efficiency due to their larger aspect ratios and unique cellular internalization approach of 2D materials. A mild thermotherapy induced by ultrasmall CuS nanoparticles can further promote the cellular uptake and improve chemotherapy efficacy. The in vitro and in vivo experimental results reveal that the theranostic nanoplatform based on degradable MONSs has excellent biocompatibility and anticancer effects. Therefore, MONSs are expected to be a competitive alternative to existing silica-based nanomaterials in antitumor treatment.

Acid-Responsive and Biologically Degradable Polyphosphazene Nanodrugs for Efficient Drug Delivery.

To enhance the therapeutic effects and reduce the damage to normal tissues in cancer chemotherapy, it is indispensable to develop drug delivery carriers with controllable release and good biocompatibility. In this work, acid-responsive and degradable polyphosphazene (PPZ) nanoparticles were synthesized by the reaction of hexachlorotripolyphosphonitrile (HCCP) with 4-hydroxy-benzoic acid (4-hydroxy-benzylidene)-hydrazide (HBHBH) and anticancer drug doxorubicin (DOX). The controlled release of DOX could be realized based on the acid responsiveness of acylhydrazone in HBHBH. Experimental results showed that polyphosphazene nanoparticles remained stable in the body's normal fluids (pH ∼ 7.4), while they were degraded and controllable release of DOX in an acidic environment such as tumors (pH ∼ 6.8) and lysosome and endosome (∼5.0) in cancer cells In particular, the doxorubicin (DOX)-loading ratio was fair high and could be tuned from 10.6 to 52.6% by changing the dosing ratio of DOX to HBHBH. Meanwhile, the polyphosphazene nanodrugs showed excellent toxicity to tumor cells and reduced the side effect to normal cells both in vitro and in vivo due to their enhanced permeability and retention (EPR) effect and pH-sensitive degradation properties. Therefore, the constructed pH-sensitive drug delivery system has great potential for cancer chemotherapy.

Design of light/ROS cascade-responsive tumor-recognizing nanotheranostics for spatiotemporally controlled drug release in locoregional photo-chemotherapy

Carrier-free nanotheranostics with high drug loading and no carrier-related toxicity are highly promising cancer therapy agents. However, the limited tumor accumulation and poorly controlled drug release of these nanotheranostics continue to be major challenges that restrict clinical applications. In this study, we develop a tumor-recognizing carrier-free nanotheranostic with light/reactive oxygen species (ROS) cascade-responsiveness for spatiotemporally selective photo-chemotherapy. The nanotheranostic is constructed by co-assembly of the indocyanine green (ICG) photosensitizer and the mannose-thioketal-doxorubicin conjugate (MAN-TK-DOX) (abbreviated as IMTD), efficiently preventing premature DOX leakage during blood circulation while reducing nonspecific damage to normal tissues/cells. Once accumulated in tumor tissues, IMTD rapidly diffuses into cancer cells via lectin receptors-mediated endocytosis. Photoacoustic/fluorescence-imaging-guided laser irradiation induces local hyperthermia and ROS generation in tumor cells, thereby promoting apoptosis. Together, the ICG-generated ROS and the endogenous ROS in cancer cells synergistically enhance DOX release, resulting in more efficient chemotherapeutic effects. The in vitro and in vivo results consistently demonstrate that IMTD achieves superior tumor accumulation, highly controllable drug release, and synergetic photo-chemotherapy. Therefore, the co-assembly of an ROS-sensitive targeting ligand-chemodrug conjugate and a photosensitizer could be used to develop spatiotemporally light-activatable nanotheranostics for precision cancer therapy. Statement of significanceSynergistic phototherapy and chemotherapy have been considered as a promising cancer treatment modality to maximize the therapeutic efficacy. Unfortunately, most nanodrugs consisting of chemotherapeutic drug and photosensitizer suffer from suboptimal tumor accumulation and poorly controlled drug release, which results in reduced therapeutic outcome. In this study, Mannose (MAN) was conjugated to the anticancer drug doxorubicin (DOX) by a ROS-sensitive thioketal linker (TK), the obtained amphiphilic MAN-TK-DOX could serve as an ideal self-carrier material to deliver photosensitizer, thus to achieve high-efficient tumor-targeting, spatiotemporal controlled drug release, and superior antitumor effect. We believe that the ROS-sensitive amphiphilic targeting ligand-chemodrug conjugate could be developed as a universal approach for designing tumor-targeted nanodrugs with precisely controlled drug release.

Preparation and Characterization of Cassava Starch Acetate–Poly Caprolactin Nanocomposites for Controlled Release of Drug Doxorubicin

Preparation and Characterization of Cassava Starch Acetate–Poly Caprolactin Nanocomposites for Controlled Release of Drug Doxorubicin

Doxorubicin-Loaded Bi-PEG Nanoparticles as Novel Chemo-Photothermal Nanoagents for Efficiently Killing Cancer Cells.

The chemo-photothermal therapy has been proved to be one of efficient strategies for destroying cancer cells, and the prerequisite is to develop photothermal nanoagents with drug-loading capacity. However, most of the current chemo-photothermal nanoagents have multiple structures which require complex synthetic process, undoubtedly hindering their bioapplication. Herein, we prepared PEGylated Bi nanoparticles and loaded with the model drug doxorubicin (DOX), forming DOX@Bi-PEG nanoparticles. Bi-PEG nanoparticles were firstly synthesized through a rapid reduction method and then coated with PEGylated phospholipids, exhibiting strong NIR absorption, high photothermal conversion efficiency of 49.4%, DOX-loading efficiency of 22.8% as well as low cytotoxicity. After incubation with 4T1 cells, DOX@Bi-PEG nanoparticles can be uptaken by cells and then release DOX within cells for chemotherapy. Furthermore, when exposed to 1064 nm laser, these nanoparticles can produce enough heat for photothermal ablating cancer cells. Therefore, the present DOX@Bi-PEG nanoparticles can be served as novel and efficient nanoagents for chemophotothermal therapy of cancer cells.

PH/redox/UV irradiation multi-stimuli responsive nanogels from star copolymer micelles and Fe3+ complexation for “on-demand” anticancer drug delivery

Multi-stimuli responsive nanogels, as promising drug carriers for “on-demand” drug delivery, are expected to provide promising prospects for tumour treatment. Herein, new pH/redox/UV irradiation multi-stimuli responsive nanogels, based on polymer micelles self-assembled by six-arm star copolymer of 6AS-PCL-PAA-PPEGMA, were prepared by the complexation of ferric ions (Fe3+) and the carboxyl groups in the polymer micelles. The spherical structure of the polymer micelles, with particle size around 80–110 nm and zeta potential of −30.19 mV, was more conducive to crosslinking with Fe3+ and quickly formed nanogels with the bigger size around 150–200 nm. The DOX-loaded nanogels were obtained by introducing the anticancer drug doxorubicin (DOX) in the nanogels preparation process with a drug loading content (DLC) of 12.04%. Under the exposure to UV, an introduction of a reducing agent (GSH) and a pH response from the PAA block, the nanogels underwent decrosslinking, followed by rapid DOX release (82.1% at 116 h). Moreover, the DOX-loaded nanogels not only could be taken up quickly by HepG2 cells but also inhibited the proliferation of the cells. Hence, these results demonstrated the high potential of the prepared 6AS-PCL-PAA-PPEGMA nanogels for “on-demand” anticancer drug delivery.

Selenium-Containing Nanoparticles Combine the NK Cells Mediated Immunotherapy with Radiotherapy and Chemotherapy.

Considering the limited clinical benefits of individual approaches against malignancy, natural killer (NK) cell-mediated immunotherapy is increasingly utilized in combination with radiotherapy and target therapeutics. However, the interplay of targeted agents, immunotherapy, and radiotherapy is complex. An improved understanding of the effect of chemotherapy or radiotherapy on specific molecular pathways in immune cells would help to optimize the synergistic antitumor efficiency. In this study, the selenium-containing nanoparticles (NPs) could deliver the chemotherapeutic drug doxorubicin (DOX) to tumor sites by systemic administration. Radiation stimuli facilitate DOX release and enhance chemotherapy efficiency. Moreover, radiation could oxidize diselenide-containing NPs to seleninic acid, which have both synergistic antitumor effect and immunomodulatory activity through enhancing NK cells function. These results indicate that the selenium-containing NPs would be a potential approach to achieve simultaneous treatments of immunotherapy, chemotherapy, and radiotherapy by a simple but effective method.

Construction of Protein-mediated Copper Sulfide Bonded Mesoporous Silica Nanoparticles Vector for Chemo-photothermal Synergistic Therapy of Cancer

Abstract Bovine serum albumin-mediated copper sulfide nanocomplex (BSA/CuS) was modified on the mesoporous silica (MSN) loaded with chemotherapeutic drug doxorubicin (DOX) by amide bond to prepare a new drug carrier MSN-DOX@BSA/CuS. The disulfide bond of blocking agent BSA broke down after the redox reaction with glutathione, resulting in the MSN pore exposure and release of DOX. As a photothermal reagent, CuS could convert light energy into heat for photothermal therapy. UV-Vis-NIR absorption spectra were used to investigate the absorption properties of the carrier. The results showed that the carrier had strong absorption in the range of 800–1100 nm and could realize the photothermal conversion under the near infrared light. In addition, MSN@BSA/CuS was incubated with cancer cells and showed no cytotoxicity. When MSN-DOX@BSA/CuS was added, the relative survival rate of the cells decreased to 49%. After the extra laser, only 18% cells survived. The above results showed that the synthesized nano drug carrier could realize the synergistic treatment of photothermal therapy and chemotherapy, and effectively improve the treatment efficiency of cancer.

Composite phospholipid-coated hollow mesoporous silica nanoplatform with multi-stimuli responsiveness for combined chemo-photothermal therapy

Chemo-photothermal therapy can improve the therapeutic effects of simple chemotherapy with the help of cytotoxic heat generated by photothermal therapy. In this paper, a novel nanoplatform based on hollow mesoporous silica (HMSN) was constructed, which could achieve multi-stimuli-responsive release through chemo-photothermal interaction. Cypate as a NIR photothermal agent was conjugated to the outer surface of HMSN by disulfide bonds. Due to the insoluble feature, Cypate imparted lipophilicity to the surface of HMSN, thereby promoting the strong encapsulation of complex phospholipid layer by hydrophobic interaction. The phospholipid layer hindered the premature release of the model drug doxorubicin (DOX), prolonged the circulation time in vivo, and improved the biocompatibility and stability in physiological environment. Under glutathione, acidic conditions and NIR irradiation, the release of DOX was significantly accelerated, indicating that DOX/HMSN-CyL exhibited redox/pH/NIR multi-stimuli in response to drug release. Cytotoxicity experiments have proved that combination therapy induced the maximum levels of cell killing. Furthermore, combination index of DOX/HMSN-CyL was 0.26, demonstrating the chemo-photothermal synergetic therapy. Multicellular tumor spheroid experiments were also performed, and the same trend was showed. In summary, this novel nanoplatform has broad application prospects as a drug delivery system for combination therapy.

PH/Reduction Dual-Stimuli-Responsive Cross-Linked Micelles Based on Multi-Functional Amphiphilic Star Copolymer: Synthesis and Controlled Anti-Cancer Drug Release.

Novel approach has been constructed for preparing the amphiphilic star copolymer pH/reduction stimuli-responsive cross-linked micelles (SCMs) as a smart drug delivery system for the well-controlled anti-tumor drug doxorubicin (DOX) release. The SCMs had a low CMC value of 5.3 mg/L. The blank and DOX-loaded SCMs both had a spherical shape with sizes around 100–180 nm. In addition, the good stability and well pH/reduction-sensitivity of the SCMs were determined by dynamic light scattering (DLS) as well. The SCMs owned a low release of DOX in bloodstream and normal tissues while it had a fast release in tumor higher glutathione (GSH) concentration and/or lower pH value conditions, which demonstrates their pH/reduction dual-responsiveness. Furthermore, we conducted the thermodynamic analysis to study the interactions between the DOX and polymer micelles in the DOX release process. The values of the thermodynamic parameters at pH 7.4 and at pH 5.0 conditions indicated that the DOX release was endothermic and controlled mainly by the forces of an electrostatic interaction. At pH 5.0 with 10 mM GSH condition, electrostatic interaction, chemical bond, and hydrophobic interactions contributed together on DOX release. With the low cytotoxicity of blank SCMs and well cytotoxicity of DOX-loaded SCMs, the results indicated that the SCMs could form a smart cancer microenvironment-responsive drug delivery system. The release kinetic and thermodynamic analysis offer a theoretical foundation for the interaction between drug molecules and polymer matrices, which helps provide a roadmap for the oriented design and control of anti-cancer drug release for cancer therapy.

Nanocomposites of ionic copolymer integrating Gd-containing polyoxometalate as a multiple platform for enhanced MRI and pH-response chemotherapy.

This article describes the fabrication of nanosized paramagnetic drug carriers via the assembly of a pH-responsive hydrophilic block copolymer poly(polyethylene glycol methyl ether methacrylate)-b-poly(methacrylic acid-co-trimethyl ammonium bromide propyl methacrylate) (PPMT) and polyoxometalate K13[Gd(β2-SiW11O39)2] (GdSiW11) through electrostatic interaction. Owing to the hydrophilicity, large molecular weight, and high content of the GdSiW11 cluster bearing in the nanocomposites, the organic-inorganic nanocomposite exhibited an impressive longitudinal relaxivity as a contrast agent for magnetic resonance imaging (MRI). The surplus negative charges from the polyoxometalate cluster in the polymer nanocomposites facilitated the capture of the anti-tumor drug doxorubicin (DOX). The DOX-loaded nanocomposites were stable under the physiological environment, whereas a responsive release of DOX was achieved at pH values similar to the tumor microenvironment due to the regulation of the polyoxometalate and carboxyl groups. The DOX-loaded PPMT2-GdSiW11 nanocomposites were observed to enrich effectively at tumor sites through MRI after intravenous injection. Furthermore, the DOX-loaded composites manifested enhanced in vivo anti-tumor therapeutic efficacy and sustainable circulation time of more than 5 h, which were favourable for imaging measurement. With the advantages of the designed composite system, the present experiments propose a strategy for developing a new multiple imaging-drug delivery-local therapy platform for synergistic diagnosis and therapy.

Palladium nanosheet-knotted injectable hydrogels formed via palladium-sulfur bonding for synergistic chemo-photothermal therapy.

Nanoparticle (NP)-based hydrogels that can introduce synergistic advantages to the novel three-dimensional scaffold have garnered much attention recently. However, the application of NP-crosslinked hydrogels still remains challenging due to the complicated synthesis and/or modification of the NPs and the changed properties of the NPs after gelation. Herein, a novel palladium nanosheet (Pd NS)-based hydrogel (Pd Gel) with Pd NSs as crosslinkers was obtained by simply mixing Pd NSs with thiol-terminated four-arm polyethylene glycol (4arm-PEG-thiol). It was found that the formed Pd Gel was injectable, possibly due to the dynamic Pd-S bonds formed between Pd NSs and 4arm-PEG-thiol. In addition, compared with free Pd NSs, the Pd NSs within the hydrogel exhibited a significantly higher stability. We have further demonstrated that the formed hydrogel could encapsulate the commonly used anticancer drug doxorubicin (DOX) to form DOX@Pd Gel for combined chemo-photothermal therapy. Particularly, Pd NSs with a high absorption in the near-infrared (NIR) region could convert the energy of NIR laser into heat with a high efficiency, which is beneficial for photothermal therapy. Moreover, DOX@Pd Gel could maintain a sustainable release of DOX and the NIR laser irradiation could accelerate this drug release process. Then, the explosively released DOX and the hyperthermia generated from Pd NSs under NIR laser irradiation acted in a synergistic way to realize the combined therapeutic effect of the chemo-photothermal treatment. Finally, the in vivo anticancer effect and safety of the combined therapy were also verified by the tumor-bearing mouse model. Taken together, this work constructs a NP-crosslinked, NIR laser-activatable and injectable photothermal hydrogel via dynamic Pd-S bonding, and demonstrates that the hydrogel allows us to release DOX more precisely, eliminate tumor more effectively and inhibit tumor metastasis more persistently, which will advance the development of novel anticancer strategies.

LDH-stabilized ultrasmall iron oxide nanoparticles as a platform for hyaluronidase-promoted MR imaging and chemotherapy of tumors.

Development of unique theranostic nanoplatforms for tumor imaging and therapy remains an active topic in current nanomedicine. Here, we designed a novel targeted theranostic nanoplatform for enhanced T1-weighted magnetic resonance (MR) imaging-guided chemotherapy by constructing layered double hydroxide (LDH)-stabilized ultrasmall iron oxide (Fe3O4) nanoparticles with hyaluronic acid (HA) modified as targeting agents, and anticancer drug doxorubicin (DOX) loaded with a high loading efficiency.Methods: The structure and release property of LDH-Fe3O4-HA/DOX nanoplatforms were characterized systematically. B16 melanoma cells with CD44 receptors overexpressed were used as model cells to determine the biocompatibility, targeting capability, and therapeutic efficiency of nanoplatforms. For in vivo experiment, hyaluronidase (HAase) pretreatment was combined with nanoplatform administration to investigate the MR imaging and chemotherapeutic effect.Results: The LDH-Fe3O4-HA nanohybrids possess good colloidal stability and cytocompatibility, display an r1 relaxivity 10-fold higher than the pristine ultrasmall Fe3O4 (4.38 mM-1 s-1 vs 0.42 mM-1 s-1), and could release drug in a pH-responsive manner. In vitro experiments demonstrate that LDH-Fe3O4-HA/DOX nanohybrids are able to specifically target B16 cells overexpressing CD44 receptors and effectively release DOX to nucleus. In vivo results show that with the pretreatment of tumor tissue by HAase to degrade the overexpressed HA in extra-cellular matrix, the designed nanoplatforms have a better tumor penetration for significantly enhanced MR imaging of tumors and tumor chemotherapy with low side effects.Conclusion: The designed LDH-Fe3O4-HA/DOX nanohybrids may be developed as a novel targeted theranostic nanoplatform for enhanced T1-weighted MR imaging-guided chemotherapy of CD44 receptor-overexpressing tumors.

Dynamic-Covalent Hydrogel with NIR-Triggered Drug Delivery for Localized Chemo-Photothermal Combination Therapy.

Near-infrared (NIR) light-responsive, injectable hydrogels are among the most promising drug delivery systems for localized anticancer therapy owing to its minimally invasive administration and remote-controlled manner. However, most currently reported NIR-responsive hydrogels were usually generated through physical mixing of thermosensitive polymers and photothermal conversion agents. In this study, a novel type of dynamic-covalent hydrogel (GelPV-DOX-DBNP) with NIR light-triggered drug release behavior was rationally designed for chemo-photothermal combination treatment of tumors. Concretely, this NIR-responsive hydrogel was formed by specific benzoxaborole-carbohydrate interactions between benzoxaborole (BOB)-modified hyaluronic acid (BOB-HA) and fructose-based glycopolymer (PolyFru), where photosensitizer perylene diimide zwitterionic polymer (PDS), reductant ascorbic acid (Vc), anticancer drug doxorubicin (DOX) as well as photothermal nanoparticles (DB-NPs) were encapsulated, simultaneously. Upon 660 nm light irradiation, both PDS and Vc within the designed hydrogel can convert oxygen into hydrogen peroxide, which could make hydrogel be degraded through the breakage of dynamic covalent bonds based on benzoxaborole-carbohydrate interactions, leading to NIR light-activatable release of DOX and DB-NPs from GelPV-DOX-DBNP. Furthermore, the released DB-NPs can convert 915 nm light irradiation into heat, enabling the application of GelPV-DOX-DBNP as a NIR-responsive drug delivery platform for both chemotherapy and photothermal therapy (PTT). In vivo results prove that GelPV-DOX-DBNP exhibited a markedly enhanced chemo-photothermal synergistic therapy for 4T1 tumor model mice, compared to chemotherapy alone or PTT. This work presents a new strategy to construct NIR light-responsive hydrogel as one alternative drug delivery system for anticancer applications.

Radiofrequency and Near-Infrared Responsive Core-Shell Nanostructures Using Layersome Templates for Cancer Treatment.

We report a multifunctional nanotherapeutic platform based on liposomes loaded with drug and iron oxide nanoparticles (IONs) coated with a gold nanoshell synthesized using a polyelectrolyte (layersome) soft templating technique. IONs and gold nanoshells were used to provide combined hyperthermia and triggered drug release via radio frequency (RF) or near-infrared (NIR) stimulation. IONs and the anticancer drug doxorubicin (DOX) were coencapsulated inside liposomes composed of zwitterionic phosphatidylcholine, anionic phosphatidylglycerol, and cholesterol lipids. Coating the magneto-liposomes with positively charged poly-l-lysine enriched the interface with gold anions to form a dense gold nanoshell and protected the structure against deformation and DOX cargo release during shell formation. After modification with thiol-terminated polyethylene glycol, intracellular delivery and release of DOX from the nanostructures was examined in A549 human lung cancer cells. The nanostructures retained their DOX cargo and remained in the cytosol after cellular uptake. Only when triggered by RF or NIR stimuli did the nanostructures release DOX, which then entered the cell nucleus. Compared to the single photothermal therapy or radio frequency treatment, the carriers with combined DOX and RF or NIR stimulation displayed higher therapeutic effect on A549 cells.

Graphene quantum dots-decorated hollow copper sulfide nanoparticles for controlled intracellular drug release and enhanced photothermal-chemotherapy

Graphene quantum dots (GQDs)-decorated hollow copper sulfide nanoparticles (CuS NPs) were developed as a multifunctional platform for controlled intracellular drug release and enhanced photothermal-chemotherapy. The CuS NPs were firstly synthesized to encapsulate anticancer drug doxorubicin (DOX) followed by the GQDs decoration on the surface of CuS NPs. The prepared NPs exhibited good crystal structure, uniform nanosize, excellent colloidal stability, high drug encapsulation and enhanced optical absorbance. Moreover, the drug release was successfully triggered from the DOX-CuS@GQDs NPs under high temperature and (near-infrared) NIR laser irradiation. Encouraged by this result, we moved to investigate the intracellular drug release behavior under NIR laser irradiation on MDA-MB-231 cells. The confocal images and flow cytometry analysis indicated a significant NIR-triggered DOX release within MDA-MB-231 cells after cellular uptake. Furthermore, the CuS NPs could readily convert light energy to heat to photothermally ablate the cancer cells under NIR laser irradiation, and the photothermal ablation effect was further enhanced by the capping of GQDs on CuS NPs. The combined photothermal therapy and chemotherapy of the prepared DOX-CuS@GQDs NPs also enabled a synergistic therapeutic effect on cancer cells. Therefore, the prepared DOX-CuS@GQDs NPs provided a novel promising platform for cancer therapy with controlled intracellular drug release and combined photothermal-chemotherapy.

Hyperthermia-Triggered Doxorubicin Release from Polymer-Coated Magnetic Nanorods.

In this paper, it is proposed that polymer-coated magnetic nanorods (MNRs) can be used with the advantage of a double objective: first, to serve as magnetic hyperthermia agents, and second, to be used as magnetic vehicles for the antitumor drug doxorubicin (DOX). Two different synthetic methodologies (hydrothermal and co-precipitation) were used to obtain MNRs of maghemite and magnetite. They were coated with poly(ethyleneimine) and poly(sodium 4-styrenesulfonate), and loaded with DOX, using the Layer-by-Layer technique. Evidence of the polymer coating and the drug loading was justified by ATR-FTIR and electrophoretic mobility measurements, and the composition of the coated nanorods was obtained by a thermogravimetric analysis. The nanorods were tested as magnetic hyperthermia agents, and it was found that they provided sufficiently large heating rates to be used as adjuvant therapy against solid tumors. DOX loading and release were determined by UV-visible spectroscopy, and it was found that up to 50% of the loaded drug was released in about 5 h, although the rate of release could be regulated by simultaneous application of hyperthermia, which acts as a sort of external release-trigger. Shape control offers another physical property of the particles as candidates to interact with tumor cells, and particles that are not too elongated can easily find their way through the cell membrane.

Near-infrared light-triggered degradable hyaluronic acid hydrogel for on-demand drug release and combined chemo-photodynamic therapy

In this study, an injectable and near-infrared (NIR) light-triggered ROS-degradable hyaluronic acid hydrogel platform was developed as localized delivery vehicle for photosensitizer protophorphyrin IX (PpIX) and anticancer drug doxorubicin (DOX), to achieve superior combined chemo-photodynamic therapy with light-tunable on-demand drug release. The in situ-forming hydrogel fabricated readily via the formation of dynamic covalent acylhydrazone bonds could efficiently prevent severe self-quenching effect of water-insoluble PpIX due to the covalent binding, leading to localized enhanced photodynamic therapy (PDT). Moreover, the extensive ROS generated by the hydrogel under NIR light irradiation could not only realize efficient PDT effect, but also cleave the ROS-cleavable small molecule crosslinker, inducing the desirable degradation of hydrogel and subsequent on-demand DOX release for cascaded chemotherapy. The developed versatile hyaluronic acid hydrogels have tunable properties, excellent biocompatibility, biodegradability and exhibit outstanding therapeutic effects in both in vitro cellular experiments and in vivo antitumor studies.