Drug Delivery System For Chemotherapy Research Articles

Probing the Impact of Surface Functionalization Module on the Performance of Mitoxantrone Prodrug Nanoassemblies: Improving the Effectiveness and Safety.

Prodrug nanoassemblies are emerging as a novel drug delivery system for chemotherapy, comprising four fundamental modules: a drug module, a modification module, a response module, and a surface functionalization module. Among these modules, surface functionalization is an essential process to enhance the biocompatibility and stability of the nanoassemblies. Here, we selected mitoxantrone (MTO) as the drug module and DSPE-PEG2K as surface functionalization module to develop MTO prodrug nanoassemblies. We systematically evaluated the effect of surface functionalization module ratios (10%, 20%, 40%, and 60% of prodrug, WDSPE-mPEG2000/Wprodrug) on the prodrug nanoassemblies. The results indicated that 40% NPs significantly improved the self-assembly stability and cellular uptake of prodrug nanoassemblies. Compared with MTO solution, 40% NPs showed better tumor specificity and pharmacokinetics, resulting in potent antitumor activity with a good safety profile. These findings highlighted the pivotal role of the surface functionalization module in regulating the performance of mitoxantrone prodrug nanoassemblies for cancer treatment.

Nanoparticles – A Booming Drug Delivery System in Chemotherapy

The current study proposed the “Nanoparticles -A Booming Drug Delivery System in Chemotherapy” is a Novel targeted approach which enhances the efficacy of chemotherapeutic agents by reducing the dose-related side effect as well as mortality rate a in patients due to its non-immunogenic, nontoxic nature. Drug bioavailability, drug solubility, drug biodistribution, drug resistance brought on by treatment, and nonspecific toxicity can all be improved with the development of nanoparticle chemotherapeutic drug delivery applications based on nanotechnology. It possesses active as well as passive targeting of tumour cells. Due to this reason, a wide range of chemotherapeutic agents like cisplatin, taxol, doxorubicin, and carboplatin are extensively utilized for treating cancer. Deep tissue penetration of nanoparticles is found to increase the enhanced permeability and retention (EPR) effect. There are some limitations with conventional drug delivery system which is minimized by utilizing nanoparticles as a drug delivery system. The current review has focused on targeted strategies and novel approaches in cancer treatment with nanoparticles.

Tumor-microenvironment responsive nano-carrier system for therapy of prostate cancer

Poor selectivity, low bioavailability and serious systemic side-effects have limited the application of traditional chemotherapy method for treatment of prostate cancer. Stimuli-responsive drug delivery systems for chemotherapy are mainly based on the unique characteristics of tumor microenvironment. In this study, the GSH-sensitive poly-TTG-SS@DTX NPs (DTX-loaded poly-Tetraethylene glycol nanoparticles) were designed and synthesized, which were characterized with nanosized diameter (92.8 ± 2.5 nm) and negatively charged surface charge (−24.7 ± 5.56 mV). Experiments in vitro showed that poly-TTG-SS@DTX NPs had good compatibility to healthy cells and strong anti-tumor effect because of rapid and sustained drug release of DTX from poly-TTG-SS@DTX NPs under the tumor-microenvironment condition. The cellular activity remained greater than 90% when the concentration of poly-TTG-SS NPs reached as high as 100 µg/mL treated on healthy cells. The killing effect of DTX loading NPs group on C4-2 cells was stronger than that of free anti-tumor drug and free DTX combined with the blank nano-carrier (25.21% vs 19.93% vs 20.96%). In conclusion, poly-TTG-SS@DTX NPs may provide a new therapeutic strategy for the chemotherapy of prostate cancer.Graphical

Dual-responsive targeted hollow mesoporous silica nanoparticles for cancer photodynamic therapy and chemotherapy

Surface modification of hollow mesoporous silica nanoparticles (HMSNs) with unique advantages are highly promising for drug delivery and have emerged for effective cancer treatment. In this study, functionalized nanoparticles for targeting and dual-responsive release of loaded doxorubicin hydrochloride (DOX·HCL) and indocyanine green (ICG) (labeled as ID@HCH). In addition, chitosan (CS) was conjugated onto the HMSNs as capping agents and then dialdehyde hyaluronic acid (HDA) was modified to endow the ability to target the CD44 receptor. The characterizations demonstrated that nanocarriers have been successfully constructed with excellent drug loading capacity (DL) and drug entrapment efficiency (EE). The in vitro DOX control release displayed pH/enzyme-response properties owing to the pH-dependent swelling effect of chitosan and the HDA degraded by hyaluronidases (HAase). Moreover, the results of in vitro cell experiments proved that the ID@HCH could inhibit the cancer cells viability via accurately targeting HepG2 cells and chemotherapy combined with photodynamic therapy. This study demonstrated that ID@HCH is a new promising dual-responsive drug delivery system for chemotherapy and photodynamic therapy.

Lipopeptide liposomes-loaded hydrogel for multistage transdermal chemotherapy of melanoma

Transdermal administration of chemotherapeutics into tumor tissues may be an effective treatment to reduce toxic side effects and improve patient compliance for melanoma. Herein, we report a multistage transdermal drug delivery system for chemotherapy of melanoma. In this system, dendritic lipopeptide (DLP) modified multistage targeted liposomes (Mtlip) were incorporated into the hydrogel matrix to achieve localized and sustained drug release; Ultra-deformability of Mtlip can pass through dense stratum corneum to the epidermis where melanoma is located; Virus-mimicking Mtlip enhances the payload in tumor tissues by high permeability; The positive charged Mtlip can improve cell uptake efficiency and selectively accumulate into mitochondria to increases toxic. The efficacy of this type of multistage targeted liposomes loaded hydrogel in treating melanoma was systematically evaluated both in vitro and in vivo.

Folate-conjugated thermal- and pH-responsive magnetic hydrogel as a drug delivery nano-system for “smart” chemo/hyperthermia therapy of solid tumors

A folate-conjugated pH- and thermal-sensitive magnetic hydrogel composed of poly(vinyl alcohol) (PVA), poly(N-isopropylacrylamide) (PNIPAAm), folate-conjugated poly(acrylic acid) (PAA-FA), and Fe3O4 nanoparticles (NPs) was developed as a “smart” drug delivery system (DDS) for chemo/hyperthermia therapy of cancer cells. Following fabrication, the hydrogels were incorporated with doxorubicin hydrochloride (Dox) physically. Owing to the porous structure of the polymeric matrix and strong physical interactions between the hydrogel and Dox, the developed DDS showed suitable loading (LE) and encapsulation (EE) efficiencies (7.3 ± 0.26 and 87 ± 2.6%, respectively). At pH 7.4 and 37 °C (physiological condition), low rate of drug release was observed from the DDS. At the tumor condition (lower pH and higher temperature), the DDS presented adequate pH- and thermal-responsive drug release behavior. Cytotoxicity of the Dox-loaded DDS in chemotherapy and hyperthermia/chemotherapy against MCF-7 cells was evaluated by MTT assay. The developed DDS showed synergic cancer therapy process by combination of chemotherapy and hyperthermia approaches.

Mitochondria-acting carrier-free nanoplatform self-assembled by α-tocopheryl succinate carrying cisplatin for combinational tumor therapy.

Unsatisfactory drug loading capability, potential toxicity of the inert carrier and the limited therapeutic effect of a single chemotherapy drug are all vital inhibitory factors of carrier-assisted drug delivery systems for chemotherapy. To address the above obstacles, a series of carrier-free nanoplatforms self-assembled by dual-drug conjugates was constructed to reinforce chemotherapy against tumors by simultaneously disrupting intratumoral DNA activity and inhibiting mitochondria function. In this nanoplatform, the mitochondria-targeting small-molecular drug, α-tocopheryl succinate (TOS), firstly self-assembled into nanoparticles, which then were used as the carrier to conjugate cisplatin (CDDP). Systematic characterization results showed that this nanoplatform exhibited suitable particle size and a negative surface charge with good stability in physicochemical environments, as well as pH-sensitive drug release and efficient cellular uptake. Due to the combined effects of reactive oxygen species (ROS) generation by TOS and DNA damage by CDDP, the developed nanoplatform could induce mitochondrial dysfunction and elevated cell apoptosis, resulting in highly efficient anti-tumor outcomes in vitro. Collectively, the combined design principles adopted for carrier-free nanodrugs construction in this study aimed at targeting different intracellular organelles for facilitating ROS production and DNA disruption can be extended to other carrier-free nanodrugs-dependent therapeutic systems.

Synthesis and Therapeutic Potential of Nanoceria against Cancer: An Update.

Applications of nanoceria in the biomedical field are quite promising, as previous data has shown potential use of nanoceria as therapeutics via radical scavenging and oxidative stress mitigating properties. But, still, there are contradicting reports regarding nanoceria activity, mode of action, and in vitro toxicity in the cell. There are different nanoceria synthesis methods and Ligands for functionalization and loading of nanoceria into drugs for targeted drug delivery. Redox chemistry of nanoceria exerts their anticancer properties through apoptosis and oxidative stress as it can switch between Ce3+ and Ce4+ and act as free radical scavengers. For breast cancer treatment, cerium oxide nanoparticles (CeONPs) can act as protectant for healthy cells against on-going radiotherapy. Similarly, CeONPs were used to make pancreatic cancer cells more sensitive to radiation damage setting them on the apoptotic pathway. Herein, the study reflects the use of nanoceria as a drug delivery system in chemotherapy due to its efficiency in acidic pH and oxidase activity in the microenvironment. A controlled drug delivery system was adapted using a nano-complexes of AMD-GCCNP-DOX, which were then employed against the retinoblastoma cells from the human eye to target the overexpressing chemokine receptor 4 (CXCR4). In radiotherapy, nanoceria acts as radioprotectants due to their free radical scavenging property and inhibit the proliferation and migration of gastric cancer. This paper summarizes the synthesis methods and application of nanoceria in cancer.

A dual stimuli-responsive star-shaped nanocarrier as de novo drug delivery system for chemotherapy of solid tumors

A novel pH- and temperature-responsive star-shaped terpolymer, namely star shaped-poly(e-caprolactone)-grafted-[poly(N,N′-dimethylamino)ethyl methacrylate-block-poly(N-isopropylacrylamide)] [s-PCL-g-(PDMAEMA-b-PNIPAAm)], was synthesized by combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP), and its potential as smart drug delivery system (DDS) for chemotherapy of solid tumors (human breast cancer) was investigated preliminary. The structure of the fabricated polymers were characterized using Fourier transform infrared (FTIR) and proton magnetic resonance (1H NMR) spectroscopies. The average molecular weights of the synthesized polymers were calculated using both 1H NMR spectroscopy and gel permeation chromatography (GPC) analysis. The self-assembly behavior of the fabricated s-PCL-g-(PDMAEMA-b-PNIPAAm) terpolymer under pH and thermal stimuli were investigated using dynamic light scattering (DLS) equipment. The methotrexate (MTX) loading capacity of the fabricated DDS was calculated to be 36.9 ± 4.1%. As pH- and thermal-triggered drug release behavior results, at pH 5 and temperature of 41 °C, the developed DDS exhibited higher drug release value, which qualified it for cancer chemotherapy according to abnormal environmental feature of cancerous cells. The MTX-loaded terpolymer exhibited higher anticancer efficiency in comparison with free MTX especially in time period of 48 h, mainly due to its slow drug release behavior as well as long circulation time of the developed DDS.

In vitro and in vivo characteristics of doxorubicin-loaded cyclodextrine-based polyester modified gadolinium oxide nanoparticles: a versatile targeted theranostic system for tumour chemotherapy and molecular resonance imaging

β-Cyclodextrine-based polyester was coated on the surface of gadolinium oxide nanoparticles (NPs) and then functionalised with folic acid to produce an efficient pH-sensitive targeted theranostic system (Gd2O3@PCD-FA) for doxorubicin delivery and magnetic resonance imaging (MRI). Gd2O3@PCD-FA was fully characterised by FTIR, vibrating sample magnetometer, TGA, XRD, SEM and TEM analyses. The dissolution profile of DOX showed a pH sensitive release. No significant toxicity was observed for the targeted NPs (Gd2O3@PCD-FA) and DOX-loaded NPs inhibiting M109 cells viability more efficiently than free DOX. Moreover, the negligible hemolytic activity of the targeted NPs showed their appropriate hemocompatibility. The preferential uptake was observed for the developed Gd2O3@PCD-FA-DOX NPs in comparison with Dotarem using T1- and T2-weighted MRI in the presence of folate receptor-positive and folate receptor-negative cancer cells (M109 and 4T1, respectively). Furthermore, in vivo studies revealed that Gd2O3@PCD-FA-DOX not only exhibited considerably relaxivity performance as a contrast agent for MRI, but also improved in vivo anti-tumour efficacy of the system. The results suggest that Gd2O3@PCD-FA-DOX improves its therapeutic efficacy in the treatment of solid tumours and also reduces the adverse effects, so it could be proposed as a promising drug delivery system for chemotherapy and molecular imaging diagnosis in MRI.

Fabrication of a hydrophobic smart nanocontainer with pH-sensitive surface activation for controlled release

A hydrophobic pH sensitive nanocontainer was fabricated using smart surfaces covalently attached to a porous alumina support. The smart surface was synthesized using a mixture of aliphatic and aminated silanes and optimized to be hydrophobic at pH<7 and hydrophilic at pH<5. The hydrophobic nanocontainer thus synthesized was able to retain a cargo of the model molecule safranine at neutral pH. When pH decreased, safranine was liberated at a high rate due to the large pores of the alumina. It is expected that the nanocontainer here presented could constitute the basis of a cancer treatment as an effective drug delivery system in chemotherapy.

Recent advancements in two‐dimensional nanomaterials for drug delivery

Different from conventional zero-dimensional (0D) and one-dimensional (1D) counterparts, two-dimensional (2D) nanomaterials show unique properties resulting from their specific structure and morphology. In recent years, broad interest has been focused on the exploration of 2D nanomaterials for drug delivery, which benefits greatly to various disease treatments due to the superior properties of 2D nanomaterials. The fast development of 2D-based drug delivery systems provides great potential for biomedical studies. In this review, a case-by-case analysis was carried out on the state-of-the-art 2D nanomaterials-based drug delivery systems, which possesses great significance to the further biomedical development of 2D nanomaterials. For the purpose of discussing the special advantages of these novel drug delivery systems, this review is organized according to the different types of the latest 2D nanomaterials and their loading capacity towards various cargos. Special emphasis will be located on the application of these 2D nanomaterials-based drug delivery systems in chemotherapy, gene therapy, and immunotherapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies.

When polymers meet carbon nanostructures: expanding horizons in cancer therapy.

The development of hybrid materials, which combine inorganic with organic materials, is receiving increasing attention by researchers. As a consequence of carbon nanostructures high chemical versatility, they exhibit enormous potential for new highly engineered multifunctional nanotherapeutic agents for cancer therapy. Whereas many groups are working on drug delivery systems for chemotherapy, the use of carbon nanohybrids for radiotherapy is rarely applied. Thus, nanotechnology offers a wide range of solutions to overcome the current obstacles of conventional chemo- and/or radiotherapies. Within this review, the structure and properties of carbon nanostructures (carbon nanotubes, nanographene oxide) functionalized preferentially with different types of polymers (synthetic, natural) are discussed. In short, synthesis approaches, toxicity investigations and anticancer efficacy of different carbon nanohybrids are described.

A high therapeutic efficacy of polymeric prodrug nano-assembly for a combination of photodynamic therapy and chemotherapy

Combination of photodynamic therapy and chemotherapy has been emerging as a new strategy for cancer treatment. Conventional photosensitizer tends to aggregate in aqueous media, which causes fluorescence quenching, reduces reactive oxygen species (ROS) production, and limits its clinical application to photodynamic therapy. Traditional nanoparticle drug delivery system for chemotherapy also has its disadvantages, such as low drug loading content, drug leakage, and off-target toxicity for normal tissues. Here, we developed a reduction-sensitive co-delivery micelles TB@PMP for combinational therapy, which composed of entrapping a red aggregation-induced emission fluorogen (AIEgen) for photodynamic therapy and PMP that contains a reduction-sensitive paclitaxel polymeric prodrug for chemotherapy. AIEgen photosensitizer illustrates a much improved photostability and ROS production efficiency in aggregate state and PMP loads a high dose of paclitaxel and carries a smart stimuli-triggered drug release property. This co-delivery system provides a better option that replaces AIEgen photosensitizer for cancer diagnosis and therapy.

Combined Chemo-photothermal Antitumor Therapy Using Molybdenum Disulfide Modified with Hyperbranched Polyglycidyl

In the treatment of cancers, molybdenum disulfide (MoS2) has shown great potential as a photoabsorbing agent in photothermal therapy and also as an antitumor drug delivery system in chemotherapy. However, the poor dispersibility and stability of MoS2 in aqueous solutions limit its applications in cancer therapy. To overcome the shortcomings, MoS2 was modified mainly by surface adsorption of linear polymers, such as chitosan and poly(ethylene glycol). As reported, the linear polymers could be more rapidly cleared from blood circulation than their branched counterparts. Herein, we developed hyperbranched polyglycidyl (HPG)-modified MoS2 (MoS2-HPG) by absorbing HPG on the MoS2 surface. The MoS2-HPG as a novel photoabsorbing agent was also used as a nanoscaled carrier to load antitumor drug doxorubicin hydrochloride (DOX) (MoS2-HPG-DOX) for combined chemo-photothermal therapy. The physicochemical and photothermal properties of MoS2-HPG were measured, and the results indicate that MoS2-HPG had good dispersion and stability in aqueous solutions and also high photothermal conversion efficiency. MoS2-HPG displayed good biocompatibility in hemocompatibility and cytotoxicity evaluations in vitro. Furthermore, the combined chemo-photothermal therapy using MoS2-HPG-DOX demonstrated better anticancer effect than the individual chemotherapy or photothermal therapy alone. From the results, MoS2-HPG with combined chemo-photothermal therapy could be developed as a promising therapeutic formulation for clinical cancer treatment.

Novel nanoparticle delivery systems for rifampicin: an effective strategy against tuberculosis?

Novel nanoparticle delivery systems for rifampicin: an effective strategy against tuberculosis?

Ultrasensitive GSH-Responsive Ditelluride-Containing Poly(ether-urethane) Nanoparticles for Controlled Drug Release.

A novel ultrasensitive redox-responsive system for the controlled release of doxorubicin (DOX) was fabricated by ditelluride-containing poly(ether-urethane) copolymers. In this study, the ditelluride group was introduced for the first time into water-soluble copolymers used for drug delivery. Doxorubicin loaded in the copolymer nanoparticles can be released in a controlled manner through the cleavage of ditelluride bonds by glutathione (GSH). The ditelluride-containing poly(ether-urethane) nanoparticles were demonstrated to be biocompatible as drug delivery vehicles, therefore opening a new avenue in drug delivery systems for chemotherapy. Furthermore, the in vitro and in vivo studies revealed that the DOX-loaded ditelluride-containing poly(ether-urethane) nanoparticles exhibited efficient uptake in cancer cells, specific tumor targeting and antitumor activity, indicating their excellent potential as novel nanocarriers for drug delivery and cancer therapy.

Passage of Magnetic Tat-Conjugated Fe3O4@SiO2 Nanoparticles Across In Vitro Blood-Brain Barrier.

Delivery of diagnostic or therapeutic agents across the blood-brain barrier (BBB) remains a major challenge of brain disease treatment. Magnetic nanoparticles are actively being developed as drug carriers due to magnetic targeting and subsequently reduced off-target effects. In this paper, we developed a magnetic SiO2@Fe3O4 nanoparticle-based carrier bound to cell-penetrating peptide Tat (SiO2@Fe3O4 -Tat) and studied its fates in accessing BBB. SiO2@Fe3O4-Tat nanoparticles (NPs) exhibited suitable magnetism and good biocompatibility. NPs adding to the apical chamber of in vitro BBB model were found in the U251 glioma cells co-cultured at the bottom of the Transwell, indicating that particles passed through the barrier and taken up by glioma cells. Moreover, the synergistic effects of Tat and magnetic field could promote the efficient cellular internalization and the permeability across the barrier. Besides, functionalization with Tat peptide allowed particles to locate into the nucleus of U251 cells than the non-conjugated NPs. These results suggest that SiO2@Fe3O4-Tat NPs could penetrate the BBB through the transcytosis of brain endothelial cells and magnetically mediated dragging. Therefore, SiO2@Fe3O4-Tat NPs could be exploited as a potential drug delivery system for chemotherapy and gene therapy of brain disease.

Development of lattice-inserted 5-Fluorouracil-hydroxyapatite nanoparticles as a chemotherapeutic delivery system.

Developing an effective vehicle for cancer treatment, hydroxyapatite nanoparticles were fabricated for drug delivery. When 5-Fluorouracil, a major chemoagent, is combined with hydroxyapatite nanocarriers by interclay insertion, the modified hydroxyapatite nanoparticles have superior lysosomal degradation profiles, which could be leveraged as controlled drug release. The decomposition of the hydroxyapatite nanocarriers facilitates the release of 5-Fluorouracil into the cytoplasm causing cell death. Hydroxyapatite nanoparticles with/without 5-Fluorouracil were synthesized and analyzed in this study. Their crystallization properties and chemical composition were examined by X-ray diffraction and Fourier transforms infrared spectroscopy. The 5-Fluorouracil release rate was determined by UV spectroscopy. The biocompatibility of hydroxyapatite-5-Fluorouracil extraction solution was assessed using 3T3 cells via a WST-8 assay. The effect of hydroxyapatite-5-Fluorouracil particles which directly work on the human lung adenocarcinoma (A549) cells was evaluated by a lactate dehydrogenase assay via contact cultivation. A 5-Fluorouracil-absorbed hydroxyapatite particles were also tested. Overall, hydroxyapatite-5-Fluorouracils were prepared using a co-precipitation method wherein 5-Fluorouracil was intercalated in the hydroxyapatite lattice as determined by X-ray diffraction. Energy dispersive scanning examination showed the 5-Fluorouracil content was higher in hydroxyapatite-5-Fluorouracil than in a prepared absorption formulation. With 5-Fluorouracil insertion in the lattice, the widths of the a and c axial constants of the hydroxyapatite crystal increased. The extraction solution of hydroxyapatite-5-Fluorouracil was nontoxic to 3T3 cells, in which 5-Fluorouracil was not released in a neutral phosphate buffer solution. In contrast, at a lower pH value (2.5), 5-Fluorouracil was released by the acidic decomposition of hydroxyapatite. Finally, the results of the lactate dehydrogenase assay revealed that 5-Fluorouracil-hydroxyapatite was highly toxic to A549 cells through direct culture, this phenomenon may result from lysosomal decomposition of particles causing 5-Fluorouracil releasing. The pH-responsive hydroxyapatite-5-Fluorouracil nanoparticles have the potential to be part of a selective drug-delivery system in chemotherapy for cancer treatment.

Hepatoma-targeting and pH-sensitive nanocarriers based on a novel d-galactopyranose copolymer for efficient drug delivery

Smart nanoparticles based on the mechanisms of asialoglycoprotein (ASGP)-mediated endocytosis and pH-induced drug release were developed for the efficient treatment of hepatoma using a newly developed copolymer, methoxy-polyethylene glycols (PEG)-b-poly (d-galactopyranose) (MPEG-b-PMaIPG). The particles exhibited spherical shapes, uniform particle size distribution (100±4.43nm), negative zeta potential (−32.8±0.23mV), high drug loading (24.77±2.68%) and encapsulation efficiency (66.12±9.44%). The in vitro drug release was also investigated, resulting that the release of drug from particles depended on different pH value. In vitro cell cytotoxicity and hemolysis assays were conducted to confirm the safety of the MPEG-b-PMaIPG nanoparticles. Anticancer activity showed that DOX-loaded MPEG-b-PMaIPG nanoparticles exhibited a high antitumor activity toward HepG2 cells, which was similar to free DOX, while blank MPEG-b-PMaIPG nanoparticles were non-toxic up to a tested concentration of 1.0mg/mL. Confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) were used to verify the targeting efficiency of d-galactopyranose-modified nanoparticles. The results clearly demonstrated that d-galactopyranose-modified nanoparticles were taken up quickly by the HepG2 cells, which suggests that MPEG-b-PMaIPG nanoparticles with good biocompatibility and non-toxic for normal cells may be used as an effective cancer-targeting drug delivery system for chemotherapy.