Efficient Delivery Of Doxorubicin Research Articles

Polyacrylic acid/polyvinylpyrrolidone/iron oxide nanocarrier for efficient delivery of doxorubicin

Recently, stimuli-responsive drug delivery systems (DDS), especially pH-responsive ones, have drawn a lot of attention to overcome the unfavourable side effects of traditional cancer treatments. In this work, a nanocomposite hydrogel based on polyacrylic acid (PAA), polyvinylpyrrolidone (PVP), and iron oxide (hematite, Fe2O3) nanoparticles was developed using the water/oil/water emulsification technique for the efficient delivery of doxorubicin (DOX) drug. The synthesized nanocarrier was characterized via XRD, and FT-IR to get information about its crystalline structure and the interaction between the functional groups of the different constituents, respectively. Its size distribution and colloidal stability were investigated via DLS and zeta potential tests, and morphological study was carried out by FE-SEM. The nanoparticles were found to be uniform and monodisperse, with an average size of 319 nm and a surface charge of −30.4 mV. The incorporation of hematite increased the drug loading (48.5 %) and encapsulation efficiency (86.57 %) due to its high porosity and surface area. Drug release was tested at pH 7.4 and 5.4, corresponding to healthy and cancerous tissues, and the results demonstrated the pH responsiveness of the system, with faster release (54 % in 24 h) in the acid medium. MTT and flow cytometry tests corroborated its strong anticancer effect since the nano-platform significantly reduced the survival rate of cancer cells. The designed pH-responsive platform holds great potential for breast cancer therapy.

Aptamer-Modified Tetrahedral DNA Nanostructures as Drug Delivery System for Cancer Targeted Therapy.

Improving the selective delivery and uptake efficiency of chemotherapeutic drugs remains a challenge for cancer-targeted therapy. In this work, a DNA tetrahedron is constructed as a targeted drug delivery system for efficient delivery of doxorubicin (Dox) into cancer cells. The DNA tetrahedron is composed of a tetrahedral DNA nanostructure (TDN) with two strands of AS1411 aptamer as recognition elements which can target the nucleolin protein on the cell membrane of cancer cells. The prepared DNA tetrahedron has a high drug-loading capacity and demonstrates pH-responsive Dox release properties. This enables efficient delivery of Dox into targeted cancer cells while reducing side effects on nontarget cells. The proposed drug delivery system exhibits significant therapeutic efficacy in vitro compared to free Dox. Accordingly, this work provides a good paradigm for developing a targeted drug delivery system for cancer therapy based on DNA tetrahedrons.

A targeted drug delivery system based on E. coli ghost for inhibiting non-Hodgkin’s lymphoma

Doxorubicin (DOX) is extensively utilized in the treatment of aggressive lymphomas, while its significant toxic side effects hamper its clinical application. Hence, there is an urgent need for a safe and effective antilymphoma drug delivery system at this stage. This study successfully developed an optimal drug delivery system (R-PEG@BGs-DOX) to safe and efficient delivery of DOX to non-Hodgkin's lymphoma site. The R-PEG@BGs-DOX was prepared by modifying polyethylene glycol (PEG) and Rituximab (R) onto the surface of bacterial ghosts (BGs), which were obtained through NaOH treatment of E. coli BL21 with modulation to achieve target structures. The prepared R-PEG@BGs exhibited efficient loading of DOX, demonstrating excellent targeting properties. The R-PEG@BGs-DOX can significantly inhibit the growth of non-Hodgkin's lymphoma cells while showing minimal toxic side effects on normal tissues. These results strongly suggest that R-PEG@BGs-DOX holds great promise as an intelligent, safe, and effective drug delivery system for anti-lymphoma treatment.

A micelle-based stage-by-stage impelled system for efficient doxorubicin delivery.

Chemotherapy remains the mainstay of cancer treatment, benefiting millions of patients each year, but the side effects of chemotherapy drugs severely limit their clinical use. Doxorubicin (DOX) can cause various side effects such as heart damage and treatment-related tumors. The effective use of active and passive targeting will improve the clinical application of DOX. Here, TPGS3350 and bioactive peptides were utilized to construct a micelle-based stage-by-stage impelled efficient system (missiles) for DOX delivery (DOX missiles). By taking advantage of the EPR effect, DOX missiles are efficiently enriched at the tumor site. After being cleaved by matrix metalloproteinase2 (MMP2), the peptide (VRGD) targets tumor cells to facilitate uptake of the missiles by the tumor cells via receptor-mediated endocytosis. The intracellular activated caspase-3-catalyzed explosion of DOX missiles further enables efficient tumor killing. This study provides an efficient approach for DOX delivery and toxicity reduction.

Multifunctional Ultrasmall Theranostic Nanohybrids Developed by Ultrasonic Atomizer for Drug Delivery and Magnetic Resonance Imaging.

Theranostic nanoparticulate systems (TNPs) have shown potential in addressing problems related to spatial localization and temporally controlled release of drugs with the capabilities of real-time imaging to evaluate the progress of therapy. The current study reports the ultrasonic atomization-led synthesis of in vitro and in vivo evaluations of ultrasmall chitosan-based theranostic nanohybrid formulations with encapsulated doxorubicin (DOX) and iron-oxide magnetic nanoparticles. The nanohybrid particles are characterized using transmission electron microscopy, powder X-ray diffraction, FTIR, DOX encapsulation efficiency, in vitro release, cellular uptake, and toxicity. These formulations were also tested for the capability of invivo tumor reduction and simultaneous magnetic resonance imaging using Swiss albino mice. Ultrasonic atomizer-led synthesis resulted in chitosan-magnetic nanohybrids (CMNPs) having sizes of 15 ± 3 nm which comprise MNP of 10 ± 3 nm. The encapsulation of DOX in CMNP was around 25%, resulting in an 80% sustained release over 10 days at pH 5 and 7. CMNP was also found to be an efficient DOX delivery vehicle tested on cancer cells (HeLa). The CMNPs were able to reduce the tumor volume by 60% in 15 days. The inherent magnetic property and nanoscale size of CMNPs also provided for enhanced contrast efficiency in magnetic resonance imaging of tumors. Thus, such multifunctional theranostic nanoparticles can be an efficient tool for targeted diagnostic and therapeutic success.

Doxorubicin-conjugated siRNA lipid nanoparticles for combination cancer therapy.

Evasion of apoptosis is a hallmark of cancer, attributed in part to overexpression of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2). In a variety of cancer types, including lymphoma, Bcl-2 is overexpressed. Therapeutic targeting of Bcl-2 has demonstrated efficacy in the clinic and is the subject of extensive clinical testing in combination with chemotherapy. Therefore, the development of co-delivery systems for Bcl-2 targeting agents, such as small interfering RNA (siRNA), and chemotherapeutics, such as doxorubicin (DOX), holds promise for enabling combination cancer therapies. Lipid nanoparticles (LNPs) are a clinically advanced nucleic acid delivery system with a compact structure suitable for siRNA encapsulation and delivery. Inspired by ongoing clinical trials of albumin-hitchhiking doxorubicin prodrugs, here we developed a DOX-siRNA co-delivery strategy via conjugation of doxorubicin to the surface of siRNA-loaded LNPs. Our optimized LNPs enabled potent knockdown of Bcl-2 and efficient delivery of DOX into the nucleus of Burkitts' lymphoma (Raji) cells, leading to effective inhibition of tumor growth in a mouse model of lymphoma. Based on these results, our LNPs may provide a platform for the co-delivery of various nucleic acids and DOX for the development of new combination cancer therapies.

Fe3O4/Au/porous Au nanohybrid for efficient delivery of doxorubicin as a model drug.

Fe3O4/Au/porous Au nanohybrids being bi-functional nanoparticles with magnetic properties and high porosity, were synthesized and used for drug delivery. To achieve this purpose, after Fe3O4 nanoparticles synthesis, a gold layer coats them to increase their stability. Then, to improve the loading capacity of Fe3O4/Au nanoparticles, a shell of porous gold was synthesized on the Fe3O4/Au surface by creating an Ag-Au nanohybrid layer on Fe3O4/Au and dissolving the metallic silver atoms in HNO3 (0.01M). The DLS results show that the synthesized nanohybrid has an average size of 68.0 ± 7.7nm and a zeta potential of - 28.1 ± 0.2mV. Finally, doxorubicin (DOX), as a pharmaceutical agent, was loaded onto the Fe3O4/Au/porous Au nanohybrids. The prepared nano-drug enhanced the therapeutic efficacy of DOX on MCF-7 cancer cells compared to the free DOX. These results confirmed a 1.5 times improvement in the antitumor activity of DOX-loaded Fe3O4/Au/porous Au nanohybrids.

Printable Metal-Polymer Conductors for Local Drug Delivery.

Safe and effective local drug delivery is challenging due to complex physiological barriers that limit the entry of drugs. Here, we report the metal-polymer conductors (MPCs) for local drug delivery via iontophoresis or electroporation. The MPCs are stretchable, conductive, and biocompatible. The flexible MPCs of different geometries are used both on a dry, flat surface (skin) and a moist, curved surface (cornea) with conformability. Conformal integration with the tissues enables good mechanical/electrical properties and realizes application of electrical voltage to the target areas for local drug delivery. By iontophoresis and electroporation, the MPCs achieve efficient delivery of doxorubicin and siRNA, leading to tumor regression and inhibition of corneal neovascularization, respectively. Our work presents an efficient strategy to harness the power of the MPCs to broaden the scope of local drug delivery to dry and wet organs with different surface topography.

PH-responsive phototherapeutic poly(acrylic acid)-calcium phosphate passivated TiO2 nanoparticle-based drug delivery system for cancer treatment applications

This paper reports the hydrothermal synthesis and characterization of poly(acrylic acid)-calcium phosphate passivated TiO2 nanoparticles (TiO2@PAA-CaP NPs). The efficient loading and release of doxorubicin (DOX) from the TiO2@PAA-CaP NPs was observed at pH = 7.4 and 5.2, respectively. The loading and encapsulation amount of DOX in TiO2@PAA-CaP NPs was approximately fifteen and eight times as large as that of unfunctionalized TiO2 NPs, respectively, suggesting the PAA-CaP passivation layer enhanced the interaction between DOX and TiO2@PAA-CaP NPs. The DOX-loaded TiO2@PAA-CaP (TiO2@PAA-CaP(DOX)) NPs exhibited much faster cumulative DOX release at acidic pH = 5.2 than at neutral pH = 7.4 because of the pH-responsive dissolution properties of the PAA-CaP passivation layer. TiO2@PAA-CaP(DOX) NPs showed higher cytotoxicity towards MCF-7 tumor cells than free DOX. Confocal fluorescence microscopy and flow cytometry confirmed the enhanced cellular uptake of TiO2@PAA-CaP(DOX) NPs followed by the intracellular release of DOX. Overall, TiO2@PAA-CaP(DOX) NPs demonstrated significantly higher total cytotoxicity towards MCF-7 tumor cells under UV-A irradiation, which was attributed to a synergistic effect between efficient DOX delivery and enhanced photoinduced reactive oxygen species (ROS) generation. This study provides a facile means of synthesizing TiO2-based multifunctional nanocarriers with pH-responsive drug delivery and ROS generation essential for high efficacy therapeutic applications in cancer treatments.

Design and optimization of PEGylated silver nanoparticles for efficient delivery of doxorubicin to cancer cells

The preparation technique of silver nanoparticles (AgNPs) is essential for the efficient drug delivery system. AgNPs coated PEG were prepared and investigated to control NPs physicochemical characteristics as well as a selective delivery of doxorubicin (DOX) to the affected site with lower side effects. In this context, AgNPs chemically synthesized and coated with PEG having different molecular weights via two different methods. The optimized AgNPs-PEG were further loaded with DOX. The prepared particles were characterized for their size, shape, and DOX in vitro release in phosphate buffer of two pH conditions 5.0 and 7.4. Moreover, the cytotoxicity of the prepared nanoformulations was investigated against MCF-7 and HepG2 cell lines, also the biodistribution of AgNPs was also investigated in rats. It was found that the investigated two methods for AgNPs-PEG preparation did not show a significant difference on the AgNPs characteristics. The prepared AgNPs were spherical in shape and showed mono-dispersibility distribution with encapsulation efficiency percent approximately 95%. DOX showed higher release in pH 5.0 than that observed in pH 7.4. Moreover, the prepared system showed sustained release behavior compared to the unloaded DOX. AgNPs loaded with DOX significantly reduced the IC50% compared with AgNPs-PEGs and unloaded DOX against both MCF-7 and HepG2 cell lines. In addition, biodistribution study revealed the higher accumulation of AgNPs-PEG in liver compared to the other investigated organs. It could be concluded that the optimized AgNPs-PEG could be considered as an efficient carrier for DOX with high drug loading, sustained DOX delivery, higher synergistic cytotoxicity, and lower side effects on the other healthy cells.

PH/ROS dual-responsive supramolecular polypeptide prodrug nanomedicine based on host-guest recognition for cancer therapy

Supramolecular nanomedicine assembly combined with polypeptide prodrug could become a powerful strategy to minimize drug leakage in blood circulation and trigger sufficient drug release at tumor tissue. Here, we developed a charge-reversal amphiphilic pillar[5]arene-modified polypeptide (P5-PLL-DMA), and reactive oxygen species (ROS)-sensitive polypeptide prodrug (P-PLL-DOX) including a ROS-cleavable thioketal (TK) linker between doxorubicin (DOX) and poly(L-lysine) (PLL), which could assemble via pillar[5]arene host-guest recognition, and further encapsulate chlorin e6 (Ce6) to obtain a supramolecular polypeptide prodrug (SPP-DOX/Ce6). The chemical conjugation to load drugs of DOX and the negatively charge of SPP-DOX/Ce6 could prevent premature drug leakage, and reduce undesirable interaction with serum proteins to enhance stability under physiological conditions (pH 7.4). Simultaneously, the carried charge of SPP-DOX/Ce6 reversed from negative to positive could effectively enhance the cellular internalization for efficient DOX delivery under acidic tumor microenvironment (pH 6.5). Upon 660 nm near-infrared light (NIR) irradiation, the ROS generated by encapsulated Ce6 rapidly cleaved the TK linker to release activated DOX, inducing the tumor-specific drug delivery. This intelligent supramolecular polypeptide prodrug based on pillar[5]arene host-guest recognition represents new avenues to develop stimulus responsive prodrug for enhanced cancer therapy with minimized the side effect. Statement of significanceIn this work, a pH/ROS dual-sensitive supramolecular polypeptide prodrug (SPP-DOX/Ce6) was developed to minimize drug leakage in blood circulation and trigger sufficient drug release at tumor tissue. The chemical conjugation to load drugs of DOX via a ROS-cleavable thioketal (TK) linker and the distinctive charge-reversal capacity of SPP-DOX/Ce6 significantly enhances the stability under physiological conditions (pH 7.4), while facilitates cellular uptake at tumor site (pH 6.8). Upon 660 nm near-infrared light (NIR) irradiation, the ROS generated by encapsulated Ce6 induces the rapid cleavage of TK linker to release activated DOX, achieving a tumor-specific drug delivery. This intelligent supramolecular polypeptide prodrug SPP-DOX/Ce6 provides an effective strategy to construct stimulus responsive prodrug for enhanced cancer therapy.

Preparation of Modified Chitosan-based Nanoparticles for Efficient Delivery of Doxorubicin and/or Cisplatin to Breast Cancer Cells.

The aim is to develop a novel pH-responsive modified chitosan-based nanoparticles system for active loading of doxorubicin (DOX) and triggered intracellular release. Nanoparticles were formed in an aqueous medium via ionic interaction between negatively charged chitosan derivative and positively charged DOX at neutral pH and then transformed in situ into cisplatin (CIS) cross-linked nanoparticles through cross-linking the formed micelles via chelation interaction between the negatively charged polymeric carrier and cisplatin. Nanoparticles were characterized in terms of particle size and zeta potential using DLS and TEM. Drug loading efficiency and encapsulation efficiency were determined based on the physio-chemical proprieties of the polymer and the amount of the cross-linking agent. In vitro release studies were performed using the dialysis method at different pHs. Finally, the cytotoxic effects of these nanoparticles were performed against the MCF-7 BrCA cell line under different pHs. The average particle size of polymer alone and DOX nanoparticles was 277.401 ± 13.50 nm and 290.20 ± 17.43 nm, respectively. The zeta potential was -14.6 ± 1.02 mV and -13.2 ± 0.55 mV, respectively, with a low polydispersity index. Drug loading and encapsulation deficiencies were determined, dependent on the amount of the cross-linking agent. In vitro release studies showed that the release of DOX from these nanoparticles was pH-dependent. Moreover, results showed that the cytotoxicity magnitude of DOX-loaded nanoparticles against MCF-7 BrCA cells was higher compared with free DOX. These novel pH-sensitive nanoparticles proved to be a promising Nano-drug delivery for tumor-targeted delivery of DOX.

Mitochondria-targeted alginate/triphenylphosphonium-grafted-chitosan for treatment of hepatocellular carcinoma.

Mitochondrial targeting of anticancer drugs can effectively eradicate chemotherapy-refractory cells through different mechanisms. This work presents the rational designing of mitochondria-targeted core–shell polymeric nanoparticles (NPs) for efficient delivery of doxorubicin (DOX) to the hepatic carcinoma mitochondria. DOX was electrostatically nano-complexed with sodium alginate (SAL) then coated with mitotropic triphenylphosphonium-grafted chitosan (TPP+-g-CS) nanoshell. Polyvinyl alcohol (PVA) was co-solubilized into the TPP+-g-CS solution to enhance the stability of the developed NPs. The optimum NPs formula is composed of TPP+-g-CS (0.05% w/v) coating a DOX-SAL core complex (0.05% w/v), with 0.2% PVA relative to CS (w/w). The optimum NPs attained an entrapment efficiency of 63.33 ± 10.18%; exhibited a spherical shape with particle size of 70–110 nm and a positive surface charge which enhances mitochondrial uptake. FTIR and DSC studies results were indicative of an efficacious poly-complexation. In vitro biological experiments proved that the developed mitotropic NPs exhibited a significantly lower IC50, effectively induced apoptotic cell death and cell cycle arrest. Moreover, the in vivo studies demonstrated an enhanced antitumor bioactivity for the mitotropic NPs along with a reduced biological toxicity profile. In conclusion, this study proposes a promising nanocarrier system for the efficient targeting of DOX to the mitochondria of hepatic tumors.

Hybrid nanoparticles based on ortho ester-modified pluronic L61 and chitosan for efficient doxorubicin delivery

Tumor intrinsic or acquired multidrug resistance (MDR) is still one of the major obstacles to the success of nanomedicine. To address this, the pH-sensitive nanoparticles (L61-OE-CS) with MDR-reversal ability were prepared by the crosslinking between acid-labile ortho-ester-modified pluronic (L61-OE) and chitosan (CS) for efficient doxorubicin (DOX) delivery. The size and micromorphology of the prepared nanoparticles were observed by dynamic light scanning and scanning electron microscopy and the nanoparticles displayed a uniform spherical shape with a diameter around 200 nm. The pH-triggered morphology change of the nanoparticles was also observed by scanning electron microscope. Drug release profiles under different pH values showed that DOX release amount within 72 h reached 16% (pH 7.4) and 76.5% (pH 5.0), respectively. In vitro cellular uptake and MTT assay demonstrated that the ortho ester and pluronic-based nanoparticles had higher cytotoxicity than non-sensitive nanoparticles. In vivo antitumor experiments also proved the superiority of the dual-functional nanoparticles, and the tumor growth inhibition rate (TGI) on day 14 was higher than 80%. Therefore, L61-OE-CS nanoparticles have great potential to be used as drug carriers in anticancer therapy.

Dual-responsive doxorubicin-loaded nanomicelles for enhanced cancer therapy

BackgroundThe enhancement of tumor retention and cellular uptake of drugs are important factors in maximizing anticancer therapy and minimizing side effects of encapsulated drugs. Herein, a delivery nanoplatform, armed with a pH-triggered charge-reversal capability and self-amplifiable reactive oxygen species (ROS)-induced drug release, is constructed by encapsulating doxorubicin (DOX) in pH/ROS-responsive polymeric micelle.ResultsThe surface charge of this system was converted from negative to positive from pH 7.4 to pH 6.8, which facilitated the cellular uptake. In addition, methionine-based system was dissociated in a ROS-rich and acidic intracellular environment, resulting in the release of DOX and α-tocopheryl succinate (TOS). Then, the exposed TOS segments further induced the generation of ROS, leading to self-amplifiable disassembly of the micelles and drug release.ConclusionsWe confirms efficient DOX delivery into cancer cells, upregulation of tumoral ROS level and induction of the apoptotic capability in vitro. The system exhibits outstanding tumor inhibition capability in vivo, indicating that dual stimuli nano-system has great potential to function as an anticancer drug delivery platform.

Folate-receptor mediated pH/reduction-responsive biomimetic nanoparticles for dually activated multi-stage anticancer drug delivery

How to overcome the cell membrane barriers and achieve release payloads efficiently in the cytoplasm have been major challenges for anticancer drug delivery and therapeutic effects with nanosystems. In this study, bovine serum albumin (BSA) was modified with folate acid and histamine, which was then used as the nanocarrier for the antitumor agent doxorubicin (DOX). The DOX-loaded nanoparticles (DOX/FBH-NPs) were prepared via a crosslinking method, and the release of DOX from these nanoparticles (NPs) exhibited pH/reduction-responsive behaviors in vitro. These NPs interacted with the folate receptor overexpressed on the cell membrane of 4T1 cells and achieved enhanced endocytosis. Afterwards, these NPs exhibited pH-responsiveness within endo-lysosomes and escaped from endosomes due to the "proton sponge" effect, and then completed release of DOX was triggered by high concentration of glutathione (GSH) in cytoplasm. Thus, DOX/FBH-NPs exhibited excellent cytotoxicity against 4T1 cells in vitro. Benefited from the enhanced permeability and retention (EPR) effect and folate receptor-mediated endocytosis, these NPs gained satisfied tumor-targeting effects in vivo and efficient delivery of DOX to tumor tissues. As a result, these NPs exhibited enhanced antitumor effects and reduced side effects in vivo. In conclusion, these BSA-based NPs modified with both folate acid and histamine showed enhanced tumor-targeting effects in vivo with good biocompatibility and intracellular pH/reduction-responsive behaviors, providing a promising strategy for the efficient delivery of antitumor agents.

Enzyme-Catalytic Self-Triggered Release of Drugs from a Nanosystem for Efficient Delivery to Nuclei of Tumor Cells.

Stimulus-responsive drug delivery nanosystems (DDSs) are of great significance in improving cancer therapy for intelligent control over drug release. However, among them, many DDSs are unable to realize rapid and sufficient drug release because most internal stimulants might be consumed during the release process. To address the plight, an abundant supply of stimulants is highly desirable. Herein, a core crosslinked pullulan-di-(4,1-hydroxybenzylene)diselenide nanosystem, which could generate abundant exogenous-stimulant reactive oxygen species (ROS) via tumor-specific NAD(P)H:quinone oxidoreductase-1 (NQO1) catalysis, was constructed by the encapsulation of β-lapachone. The enzyme-catalytic-generated ROS induced self-triggered cascade amplification release of loaded doxorubicin (DOX) in the tumor cells, thus achieving efficient delivery of DOX to the nuclei of tumor cells by breaking the diselenide bond of the nanosystem. As a result, the antitumor effect of this nanosystem was significantly improved in the HepG2 xenograft model. In general, this study offers a new paradigm for utilizing the interaction between the loaded agent and carrier in the tumor cells to obtain self-triggered drug release in the design of DDSs for enhanced cancer therapy.

Magnesium Fluoride Forms Unique Protein Corona for Efficient Delivery of Doxorubicin into Breast Cancer Cells.

Background: The efficacy of chemotherapy is undermined by adverse side effects and chemoresistance of target tissues. Developing a drug delivery system can reduce off-target side effects and increase the efficacy of drugs by increasing their accumulation in target tissues. Inorganic salts have several advantages over other drug delivery vectors in that they are non-carcinogenic and less immunogenic than viral vectors and have a higher loading capacity and better controlled release than lipid and polymer vectors. Methods: MgF2 crystals were fabricated by mixing 20 mM MgCl2 and 10 mM NaF and incubating for 30 min at 37 °C. The crystals were characterized by absorbance, dynamic light scattering, microscopic observance, pH sensitivity test, SEM, EDX and FTIR. The binding efficacy to doxorubicin was assessed by measuring fluorescence intensity. pH-dependent doxorubicin release profile was used to assess the controlled release capability of the particle-drug complex. Cellular uptake was assessed by fluorescence microscopy. Cytotoxicity of the particles and the drug-particle complex were assessed using MTT assay to measure cell viability of MCF-7 cells. Results and Discussion: Particle size on average was estimated to be <200 nm. The crystals were cubic in shape. The particles were pH-sensitive and capable of releasing doxorubicin in increasing acidic conditions. MgF2 nanocrystals were safe in lower concentrations, and when bound to doxorubicin, enhanced its uptake. The protein corona formed around MgF2 nanoparticles lacks typical opsonins but contains some dysopsonins. Conclusion: A drug delivery vector in the form of MgF2 nanocrystals has been developed to transport doxorubicin into breast cancer cells. It is pH-sensitive (allowing for controlled release), size-modifiable, simple and cheap to produce.

H2O2-responsive polymeric micelles with a benzil moiety for efficient DOX delivery and AIE imaging.

Nano drug delivery is a promising domain in biomedical theranostics and has aroused more and more attention in recent years. We report here an amphiphilic polymer TPG1, bearing a H2O2-sensitive benzil and an AIE fluorophore tetraphenylethene (TPE) unit, which is able to self-assemble into spherical nanosized micelles in aqueous solution. Doxorubicin (DOX) can be encapsulated into TPG1 micelles efficiently with the loading capability of up to 59% by weight. The benzil moiety could be cleaved via the Baeyer-Villiger type reaction in the presence of H2O2, leading to the decomposition of TPG1 micelles and release of DOX. In vitro studies indicated that DOX-loaded TPG1 micelles can be internalized by cancer cells, followed by unloading encapsulated DOX under the stimulation of H2O2. The drug release process can be monitored by the AIE fluorescence from the degradation products containing a TPE moiety. MTT assays against HeLa and HepG2 cancer cells demonstrated that DOX-loaded micelles showed good anticancer efficacy. The polymer TPG1 and the corresponding decomposed products showed great biocompatibility. Our data suggest that TPG1 has the potential to be employed for the controlled drug delivery system.

Amine-functionalized, porous silica-coated NaYF4:Yb/Er upconversion nanophosphors for efficient delivery of doxorubicin and curcumin

Upconversion nanoparticles (UCNP) with unique multi-photon excitation photo-luminescence properties have been extensively explored as novel contrast agents for low-background biomedical imaging. There is an increasing interest in employing UCNPs as carrier for drug delivery as these offers a unique opportunity to combine therapy and diagnostics in one platform (theranostics). In the present work, we report microwave-assisted synthesis of hexagonal NaYF4:Yb/Er UCNPs coated with porous silica and functionalized with amine (UCNP@mSiO2). The UCNP@mSiO2 were investigated for controlled delivery of a chemotherapeutic agent, doxorubicin (DOX, hydrophilic), and a chemosensitizing agent, curcumin (CCM, hydrophobic). The drug loading was relatively higher for DOX (17.4%), in comparison to CCM (8.1%). The cumulative drug release from DOX-loaded UCNP@mSiO2 were 30 and 41% at physiological (7.4) and tumoral (6.4) pH, following a pseudo Fickian release pattern, whereas the release from CCM-loaded UCNP@mSiO2 were 27 and 50% at pH 7.4 and 6.4, following a non-Fickian and pseudo-Fickian release patterns, respectively. Both DOX and CCM-loaded UCNP@mSiO2 exhibited pH-dependent controlled drug delivery but the effect was more pronounced for CCM, the hydrophobic chemosensitizer. Cell viability assay using HeLa cells showed that DOX-loaded UCNP@mSiO2 inhibit cell growth in a dose-dependent manner, similar to free DOX, but the cell inhibition activity of free CCM was lower than CCM passively entrapped in UCNP@mSiO2. Confocal microscopy studies revealed cell uptake of both the drug by HeLa cells. Thus, UCNP@mSiO2 exhibited the unique capability to deliver hydrophilic and hydrophobic drugs, individually. UCNP@mSiO2 carrier, equipped with theranostic capabilities, may potentially be used for pH-responsive release of chemotherapeutic agents in cancer environment.