Nano-drug Systems Research Articles

Glutathione-sensitive PEGylated curcumin prodrug nanomicelles: Preparation, characterization, cellular uptake and bioavailability evaluation

The anti-tumor efficacy of curcumin can be markedly improved by nano-drug self-delivery systems with high drug loading capacity and smart stimulus-triggered drug release in tumor cells. Herein, a type of novel, glutathione (GSH)-responsive, PEGylated prodrug nano-micelles (PPNMs) was prepared by self-assembly of curcumin-s-s-vitamin E/mPEG2k-DSPE mixture. The PPNMs (entrapment efficiency: 96.7%) was acceptably stable in water with a mean particle size of 29.84 nm. Compared with curcumin-loaded mPEG2k-DSPE nano-micelles (CUR-NMs), PPNMs showed a higher drug loading (1.68% vs 27.3%) and remarkably improved the chemical stability of curcumin in phosphate buffer saline (PBS) (pH = 7.4), 10% FBS culture medium, and rat plasma. In vitro release study showed that PPNMs could redox responsively control the release of curcumin from the prodrug. Moreover, PPNMs showed a cytotoxicity in HepG2 cells similar to that of the free curcumin; however, when the HepG2 cells were pretreated with 1 mM GSH, PPNMs displayed a markedly enhanced cytotoxicity and cellular uptake than the free curcumin. After intravenous injection, PPNMs showed an increased half-life in blood circulation (10.6-fold) and bioavailability (107-fold) compared with the free curcumin injection. Altogether, the prodrug nano-micelles represent a promising preparation for sustained and controlled delivery of curcumin with enhanced antitumor activity.

Practical aspects in size and morphology characterization of drug-loaded nano-liposomes

Size and morphology distributions are critical to the performance of nano-drug systems, as they determine drug pharmacokinetics and biodistribution. Therefore, comprehensive and reliable analyses of these properties are required by both the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). In this study, we compare two most commonly used approaches for assessing the size distribution and morphology of liposomal nano-drug systems, namely, dynamic light scattering (DLS) and cryogenic-transmission electron microscopy (cryo-TEM); an automated quantitative analysis method was developed for the latter method. We demonstrate the advantages and disadvantages of each of these two approaches for a commercial formulation of the anti-cancer drug doxorubicin - Doxil®, in which the drug is encapsulated, mostly in the form of nano-rod crystals. With increasing drug concentration, these nano-rods change the shape of the liposomes from spherical, before drug loading, to prolate (oval), post drug loading. Cryo-TEM analysis provides a detailed size distribution of both the liposomes (minor and major axes) and the nano-rod drug. Both these values are relevant to the drug performance. In this study, we show that at elevated drug concentration (2.75 mg/ml) the drug grows mainly along the major axis and that this high concentration can result, in some cases, in liposome rupture. We show that the combination of cryo-TEM and DLS constitutes a reliable tool for demonstrating the stability of the formulation in human plasma at body temperature, a characteristic that is crucial for achieving therapeutic efficacy.

Nanosystems as modulators of intestinal dapsone and clofazimine delivery

The aim of this work was to assess the feasibility of drug nanosystems combination for oral therapy of multibacillary leprosy. The anti-leprotic drugs dapsone (DAP) and clofazimine (CLZ) were incorporated within polymeric nanosystems and studied per se and in combination. DAP was loaded in Eudragit L100 nanoparticles (NPs-DAP) while CLZ was loaded in (poly(lactic-co-glycolic acid) (NPs-CLZ). The nanosystems exhibited around 200 nm in size and a drug loading of 12% for each drug. In vitro cytotoxicity on intestinal Caco-2 cells revealed that after 8 h incubation, DAP alone and within NPs were not toxic up to 100 μg mL−1, while CLZ per se was toxic, reducing cell viability to 30% at 50 μg mL−1. Caco-2 exposed to the combination of NPs-DAP (100 μg mL−1) and NPs-CLZ (50 μg mL−1) exhibited 80% of viability. Caco-2 monolayer permeability assays revealed that DAP and CLZ in the nanosystems per se or in NPs-DAP/ NPs-CLZ combination crossed the intestinal barrier. No significant differences were observed between the single nanosystems or in combination with the apparent permeability values and the amount of permeated drug. Thus, the NPs-DAP/NPs-CLZ combination seems to be a promising platform to deliver both drugs in association, representing an important step towards the improvement of multibacillary leprosy therapy.

Combined Adsorption and Covalent Linking of Paclitaxel on Functionalized Nano-Graphene Oxide for Inhibiting Cancer Cells.

Developing targeted delivery nanosystems for delivering chemotherapeutic anticancer drugs specifically to cancerous tissues with improvement in the specificity of drugs for different cancer cells can result in high therapeutic efficacy and low toxicity in healthy tissues. Herein, we proposed the synthesis of a multifunctional nanodelivery system, folic acid (FA) decorating nanographene oxide (nGO) functionalized with poly(ethylene glycol) (PEG), called pGO-FA, with good biocompatibility and good delivering performance of a hydrophobic water-insoluble anticancer drug of paclitaxel (PTX). 4-br-PEG-NH2, FA, and PTX were attached to PEG-functionalized nGO (pGO) through a combined chemical and physical force to form a nanosized complex, pGO-FA-PTX, defined as the nanodrug system. WST-8 assay in vitro illustrated that pGO-FA-PTX inhibited A2780 cells in a concentration-dependent manner. Cell viability was kept high to 60% when treated with 200 nM of free PTX. However, pGO-FA-PTX with the same dose of PTX (cell viability less than 30%) had double the cytotoxicity effect compared to free PTX. Furthermore, fluorescence observation demonstrated that pGO-FA-PTX exhibited an improved efficiency in killing A2780 cells due to the special affinity between FA and FA receptor, which has high expression in cancer cells. The strategy and method used in this study could be effective in improving both the bioavailability of PTX and therapy efficiency.

Advances in Synthesis and Application of Nanometer Drug Carriers

The main reason for the formation of nano-biotechnology is due to the penetration of nanotechnology in the biological field, nanotechnology research center is the study of nano-drug carrier. Nano-drug system targeted drug delivery to achieve drug release, increase the insoluble drugs and peptide drug bio-efficiency, reduce the toxicity and application of drugs and other aspects of the development of good prospects, and thus become one of the key research in recent years’ field. Synthesis and application of nanometer drug carriers this review is presented in recent years and its application to provide a comprehensive basis for the treatment process. Describes the nature and preparation of nano-drug carrier methods, in recent years, people have been widely concerned by scholars. Compared with the nano-drug delivery, the general pharmaceutical cannot have to extend the role of drugs, strong efficacy, and the advantages of small drug response. Nano-materials, the specific surface area, surface activity, high catalytic efficiency, surface active center, adsorption capacity and other characteristics, which has many excellent features and new features.

Localized Fe(II)-Induced Cytotoxic Reactive Oxygen Species Generating Nanosystem for Enhanced Anticancer Therapy.

The anticancer therapy on the basis of reactive oxygen species (ROS)-mediated cellular apoptosis has achieved great progress. However, this kind of theraputic strategy still faces some challenges such as light, photosensitizer and oxygen (O2) dependence. In this article, a ROS-mediated anticancer therapy independent of light, photosensitizer and oxygen was established based on a Fe2+-induced ROS-generating nanosystem. First, artemisinin (ART) was loaded in porous magnetic supraparticles (MSP) by a nanodeposition method. Then, the poly(aspartic acid)-based polymer, which consisted of dopamine, indocyanine green, and polyethylene glycol side chain, was coated onto the surface of ART-loaded MSP. When the nanoparticles entered into cancer cells, a reaction of Fe2+-mediated cleavage of the endoperoxide bridge contained in ART occurred and subsequent a large amount of ROS was generated. Moreover, a NIR light was used to effectively increase the local temperature of tumor in virtue of the superior photothermal effects of MSP, which enabled us to accelerate the ROS generation and achieved an enhanced ROS yield. The newly developed nanodrug system displayed a high level of intracellular ROS generation, leading to the desired killing efficacy against malignant cells and solid tumor. This smart nanosystem holds great potential to overcome the existing barrier in PDT and opens a promising avenue for anticancer therapy.

Phasor-Fluorescence Lifetime Imaging Microscopy Analysis to Monitor Intercellular Drug Release from a pH-Sensitive Polymeric Nanocarrier.

The design of highly efficient drug carriers, and the development of appropriate techniques to monitor their mechanism of action and therapeutic effect, are both critical for improving chemotherapy. Herein, a polymeric nanoparticle, PAH-Cit/DOX (poly(allylamine)-citraconic anhydride/doxorubicin), was synthesized and used as a nanodrug system for the efficient delivery and pH-responsive release of doxorubicin (DOX) into cancer cells. The PAH-Cit/DOX nanoparticles were stable at physiological pH but effectively released DOX under weakly acidic conditions. The release efficiency was 90.6% after 60 h of dialysis in phosphate-buffered saline at pH 5.5. Confocal images showed the rapid movement of the drug from the cytoplasm to the nucleus, indicating the effective drug release MCF-7 cells. Notably, the combination of fluorescence lifetime imaging microscopy (FLIM) and phasor analysis (phasor-FLIM) provides an approach to monitor the dynamic change of DOX fluorescence lifetime in intercellular environments. Phasor-differentiated lifetime pixel intensity in FLIM images was quantified and used to evaluate the DOX release from nanocarriers, making it possible to detect the dynamics of intracellular release and transport of DOX.

Engineering a customized nanodrug delivery system at the cellular level for targeted cancer therapy.

Drug administration customized to individual cells could intrinsically address cancer heterogeneity and provide a safe and effective method for delivering personalized treatment. To accomplish this, we developed a smart nanodrug delivery system characterized by cancer cell-targeted drug delivery and intracellular biomarker-responsive drug activation. This system was composed of a long-nicked DNA duplex formed by tandem hybridization of two extended antisense oligonucleotides whose ends were separately blocked with a cancer cell-specific aptamer, AS1411, and a replaceable anti-biomarker probe (ABP). We demonstrated that this DNA nanodrug was directed to cancer cells with the guidance power of AS1411 and then activated by the presence of a given intracellular biomarker. By using such a belt-and-braces strategy, this DNA nanodrug system could safely and efficiently accelerate apoptosis of target cancer cells. Moreover, since the expression level of biomarkers tends to indicate the specific physiological state of individual cells, biomarker-responsive activation of the nanodrug is expected to enable customized drug administration at the cellular level.

Dual-stimuli-responsive TiO x /DOX nanodrug system for lung cancer synergistic therapy.

Biological applications of nanosheets are rapidly increasing currently, which introduces new possibilities to improve the efficacy of cancer chemotherapy and radiotherapy. Herein, we designed and synthesized a novel nano-drug system, doxorubicin (DOX) loaded titanium peroxide (TiOx) nanosheets, toward the synergistic treatment of lung cancer. The precursor of TiO2 nanosheets with high specific surface area was synthesized by a modified hydrothermal process using the polymer P123 as a soft template to control the shape. TiOx nanosheets were obtained by oxidizing TiO2 nanosheets with H2O2. The anti-cancer drug DOX was effectively loaded on the surface of TiOx nanosheets. Generation of reactive oxygen species, including H2O2, ·OH and ·O2−, was promoted from TiOx nanosheets under X-ray irradiation, which is effective for cancer radiotherapy and drug release in cancer cells. In this way, chemotherapy and radiotherapy were combined effectively for the synergistic therapy of cancers. Our results reinforce the DOX loaded TiOx nanosheets as a pH sensitive and X-ray controlled dual-stimuli-responsive drug release system. The cytotoxicity, cellular uptake, and intracellular location of the formulations were evaluated in the A549 human non-small cell lung cancer cell line. Our results showed that TiOx/DOX complexes exhibited a greater cytotoxicity toward A549 cells than free DOX. This work demonstrates that the therapeutic efficacy of DOX-loaded TiOx nanosheets is strongly dependent on their loading mode and the chemotherapeutic and radiotherapy effect is improved under X-ray illumination, which provides a significant breakthrough for future applications of TiOx as a light activated drug carrier in cancer chemotherapy and radiotherapy.

Development of optimized self-nanoemulsifying lyophilized tablets (SNELTs) to improve finasteride clinical pharmacokinetic behavior

Objective: Preparation of an optimized finasteride (FSD) lyophilized tablets loaded with self-nanoemulsifying drug delivery system (SNEDDS).Significance: Enhance FSD bioavailability in male pattern baldness and benign prostatic hyperplasia.Methods: Two-step optimization was implemented to achieve the study goals. First; the mixture design was used to develop an optimized SNEDDS through which the effect of cosurfactant number of carbon atoms on SNEDDS particle size and thermodynamic stability has been tested. Second; the different tablet excipients have been used to develop an optimized self-nanoemulsifying lyophilized tablets (SNELTs). The prepared tablets have been fully characterized. Interaction among tablet components has been studied. Finally, FSD clinical pharmacokinetic has been investigated on human volunteers.Results: Anise oil and tween 80 were selected as oily phase and surfactant, respectively while different aliphatic alcohols were studied as cosurfactants. Percentages of oil, surfactant, and cosurfactants were significantly affecting SNEDDS particle size. Increasing cosurfactant number of carbon atoms achieved smaller particle size and higher stability. The optimized SNEDDS was found to contain 10.3455, 45.8972, and 43.7573% of anise oil, tween 80, and butanol, respectively. Variations in FSD cumulative release and disintegration time, from the prepared tablets, were attributed to change in the percent of plasdone XL, Avicel and silica. No interaction among components was noticed. Clinical pharmacokinetics illustrated significant enhancement in the studied parameters from the optimized lyophilized tablets loaded with drug SNEDDS when compared to marketed FSD product.Conclusion: Lyophilized tablets could be considered as a good alternative for conventional solid dosage forms especially when loaded with drug nanosystems.

Cancer Therapeutic Proficiency of Dual-Targeted Mesoporous Silica Nanocomposite Endorses Combination Drug Delivery

The cargo-loaded mesoporous silica nanoparticles (MSNs) with convenient surface modification can facilitate the development of the innovative nanodrug system. Herein, the present investigation described the electrostatically self-assembled MSNs as a nanosized drug carrier to realize potent synergistic chemotherapy based on the specificity in targeting cytoplasm and nucleus of tumor cells. In this context, the primarily constructed MSNs were subjected with anticancer drug topotecan (TPT) into its large pores. Then, the selective TAT peptide (a nuclear localization signal peptide) was anchored onto TPT-loaded MSNs (TPT-MSN). Subsequently, the positive surface of TPT-MSN-TAT was capped with negatively charged components, poly(acrylic acid) (PAA)-cRGD peptide and citraconic anhydride (CAH)-metformin (MT), and acted as a smart gatekeeper. Comparatively, PAA-cRGD attached onto MSNs serving as the targeted molecules could upsurge by invasion into cancer cells. Interestingly, the acidic pH of the lysosomal compartment in tumor cells triggers the conjugated CAH from the polymer decorated mesoporous silica (PMS) nanocomposite and could efficiently release MT into the cytoplasm. Consequently, the remaining TPT-MSN-TAT efficiently targets the nucleus and delivers the TPT to improve synergistic chemotherapeutic effects. The precisely released drugs were individually enhanced in the in vitro and in vivo cell killing efficiencies. Thus, the study provides a potential drug delivery podium through combined drugs to realize cancer cell targeting approach.

Incorporation of metal free and Ga 5,10,15,20-tetrakis(4-bromophenyl) porphyrin into Pluronic F127-folic acid micelles

ClGa 5,10,15,20-Tetrakis (4-bromophenyl) porphyrinato (ClGaTBrPP) and its metal free derivative were successfully synthesized and incorporated into Pluronic F127 polymeric micelles that has been conjugated to folic acid (FA) to form ClGaTBrPP-F127-FA (or H2TBrPP-F127-FA). For comparison, ClGaTBrPP-F127 and H2TBrPP-F127 (without FA) were also formed. The singlet oxygen quantum yield for ClGaTBrPP-F127-FA was higher (ΦΔ = 0.44) than that of H2TBrPP-F127-FA (ΦΔ = 0.37), due to the heavy atom effect of Ga in the former which encourages intersystem crossing to the triplet state. The same applies to ClGaTBrPP-F127 (ΦΔ = 0.47) and H2TBrPP-F127 (ΦΔ = 0.41). Thus, ΦΔ values decreased in the presence of FA, but still high enough for practical application of the nanodrug system. The binding constants Kb were determined to be 1.08 × 104M−1, 2.51 × 105M−1, 1.52 × 103 and 2.68 × 103 for H2TBrPP+F127-FA, ClGaTBrPP+F127-FA, ClGaTBrPP-F127 and H2TBrPP-F127, respectively. The Kp values were determined in biphasic octanol and water system.

Triple-negative breast cancer targeting and killing by EpCAM-directed, plasmonically active nanodrug systems

An ongoing need for new cancer therapeutics exists, especially ones that specifically home and target triple-negative breast cancer. Because triple-negative breast cancer express low or are devoid of estrogen, progesterone, or Her2/Neu receptors, another target must be used for advanced drug delivery strategies. Here, we engineered a nanodrug delivery system consisting of silver-coated gold nanorods (AuNR/Ag) targeting epithelial cell adhesion/activating molecule (EpCAM) and loaded with doxorubicin. This nanodrug system, AuNR/Ag/Dox-EpCAM, was found to specifically target EpCAM-expressing tumors compared to low EpCAM-expressing tumors. Namely, the nanodrug had an effective dose (ED50) of 3 μM in inhibiting 4T1 cell viability and an ED50 of 110 μM for MDA-MD-231 cells. Flow cytometry data indicated that 4T1 cells, on average, express two orders of magnitude more EpCAM than MDA-MD-231 cells, which correlates with our ED50 findings. Moreover, due to the silver coating, the AuNR/Ag can be detected simultaneously by surface-enhanced Raman spectroscopy and photoacoustic microscopy. Analysis by these imaging detection techniques as well as by inductively coupled plasma mass spectrometry showed that the targeted nanodrug system was taken up by EpCAM-expressing cells and tumors at significantly higher rates than untargeted nanoparticles (p < 0.05). Thus, this approach establishes a plasmonically active nanodrug theranostic for triple-negative breast cancer and, potentially, a delivery platform with improved multimodal imaging capability for other clinically relevant chemotherapeutics with dose-limiting toxicities, such as platinum-based or taxane-based therapies.

Abstract LB-312: Breast cancer targeting by theranostic gold nanorods

Abstract An ongoing need for new cancer therapeutics exists, especially ones that specifically home and target triple negative breast cancer (TNBC) tumors. Because TNBC does not express estrogen, progesterone, or Her2/Neu receptors, another target must be used for advanced drug delivery strategies. Here, we engineered a nanodrug delivery system consisting of silver-coated gold nanorods targeting EpCAM and loaded with doxorubicin. This novel nanodrug system, EpCAM-AuNR/Ag/Dox, was found to specifically target EpCAM-expressing tumor cells compared to low EpCAM-expressing tumors. Namely, the system had an inhibiting cell viability effective dose (ED50) of 3μM on 4T1 cells and an ED50 of 110μM for MDA-MD-231 cells. Flow cytometry indicated that 4T1 cells, on average, express two orders of magnitude more EpCAM than MDA-MD-231 cells, which correlates with our ED50 findings. Moreover, due to its thin silver coating, the AuNR/Ag allowed for detection by surface-enhanced Raman spectroscopy (SERS) and photoacoustics (PA). Analysis by both imaging detection techniques showed that the targeted nanodrug system was taken up by EpCAM-expressing cells and tumors at significantly higher rates than untargeted nanoparticles (p&amp;lt;0.05). In conclusion, our novel approach establishes a plasmonically-active nanodrug therapeutic system for TNBC and, potentially, a delivery system with improved multimodal imaging capability for other clinically approved chemotherapeutics with dose-limiting toxicities, such as platinum-based or taxane-based therapies. Citation Format: Samir V. Jenkins, Zeid A. Nima, Kieng B. Vang, Dmitry Nedosekin, Vladimir P. Zharov, Robert J. Griffin, Alexandru S. Biris, Ruud P. Dings. Breast cancer targeting by theranostic gold nanorods [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-312. doi:10.1158/1538-7445.AM2017-LB-312

Colloidal properties and in vitro evaluation of Hydroxy ethyl cellulose coated iron oxide particles for targeted drug delivery

In this study, superparamagnetic iron oxide (Fe3O4) nanoparticles were prepared for the targeted drug delivery applications by controlling the colloidal properties with a cellulosic polymer that is Hydroxy ethyl cellulose (HEC). Fe3O4 particles were treated with HEC in a variable range of polymer concentration. Rheological, electrokinetic, magnetorheological and morphological properties of the dispersions were investigated to have stable and fully covered surfaces of Fe3O4 particles by coating with HEC and obtaining non-toxic biocompatible multifunctional magnetic particles. Fully coated HEC and iron-oxide particles were characterized thermally, magnetically and tested for toxicity in vitro. Then Doxorubicin hydrochloride (DOX), which is an anticancer drug widely used for cancer therapies, was loaded onto nanoparticles and their drug loading efficiency was determined. Finally, effects of DOX-loaded particles on the cancer cells were examined to report a nano drug system which can potentially open up new possibilities in the design of therapeutic agents. Results indicated that the synthesized nanoparticles in this study could be suitable to magnetically manipulated targeted delivery systems, imaging, magnetic hyperthermia treatments.

Tumor‐Responsive Small Molecule Self‐Assembled Nanosystem for Simultaneous Fluorescence Imaging and Chemotherapy of Lung Cancer

Cancer therapeutic drugs face various transportation barriers in transit to the tumor site, making the delivery of effective drug concentrations problematic. Moreover, these drugs are very difficult to use due to their adverse off‐target effects. Thus, it is very essential to develop a drug delivery system that can deliver drugs to achieve effective local concentrations without side effects on healthy tissues. Herein, the authors report a self‐assembled nanodrug system in which hydrophobic antitumor drugs are packaged into nanoparticles to improve water solubility, tumor targeting ability, blood retention time, and chemotherapeutic effect. The nanodrugs are degraded into smaller ones when exposed to the tumor microenvironment, extravasated from leaky regions of the tumor vasculature, and displayed matrix metalloproteinase‐2 (MMP‐2)‐induced degradation and antitumor property. To construct this unique system, an amphiphilic multifunctional molecule (Pep‐Cy5) is synthesized by attaching a MMP‐2‐cleavable peptide to a hydrophobic near‐infrared dye, Cy5. Two hydrophobic anticancer drugs are conjugated to Pep‐Cy5 through hydrophobic interactions to form the self‐assembled nanodrug system. The MMP‐2‐induced degradation and hydrophobic antitumor drug interchangeability features of this nanosystem enable the hydrophobic antitumor drugs to exhibit longer blood‐retention times, improved intratumoral accumulation, fewer side effects, and higher anticancer efficacies compared with free drugs.

VIP-loaded PLGA as an anti-asthma nanodrug candidate

Poly lactic-co-glycolic acid (PLGA), a biodegradable polymer, can effectively protect encapsulated peptides from enzymatic degradation. PLGA was approved by FDA as a safe drug delivery system suitable for inhalation administration. Vasoactive intestinal peptide (VIP), a 28-amino-acid peptide, displays anti-inflammatory and anti-spasmodic effects, which can be considered as a new therapeutic option to control and treat asthma. Because of in vivo enzymatic degradation of VIP including in the lung, there is a need for an applicable delivery system. In light of this, the purpose of this study was to prepare VIP-loaded PLGA microspheres as a drug delivery system, assuming that the newly-introduced model has the ability to persist for a longer time in respiratory tracts. The PLGA microsphere was produced, and loaded with VIP as an applicable nanodrug system. A series of physiochemical properties were determined, including the morphological characteristics, average size of nanoparticles, electric charge distribution, FTIR spectroscopy absorption, and loading and releasing percentage of the nanodrug. VIP-loaded PLGA exhibited an average size of approximately 550 ± 50 nm. Additionally, the produced microsphere showed 78 % VIP release after 10 h at the pH value corresponding to bronchioalveolar microenvironment (approximately 6.5). In the present study, PLGA was formulated and used as a delivery system for VIP. Taken together, the newly-introduced nanodrug seems to be helpful for the clinical treatment of allergic asthma. PLGA nanoparticles can be considered as a potential efficient delivery system for VIP in the respiratory system.

Hybrid liposomes with cluster bomb structure for liver tumor treatment

Combining organic and inorganic drug delivery strategies in one system is expected to solve their current issues and achieve desirable functions. Based on our previous research, paclitaxel liposomes (PTX-Lips) and liposomes encapsulating paclitaxelconjugated gold nanoparticles (PTX@Au-Lips) were mixed with different volume ratios for the improved performance of liver tumor treatment. The liposomes physically mixed were found to re-construct and self-assemble into a series of hybrid liposomes having cluster bomb structure. The hybrid liposomes maintain the advantages of both PTX-Lips and PTX@Au-Lips, which demonstrate quick-andsustained drug release property in one system. Comparing to PTX-Lips, PTX@AuLips, and commercial Taxol®, the hybrid liposomes showed the most desirable performance, including (1) the highest tumor killing efficiency and longest intracellular retention; (2) the highest antitumor efficacy both in single-dose and multiple-dose treatment in a murine liver cancer model; and (3) the lowest systemic toxicity. The result obtained in this work allows the hybrid liposomes with the unique structure to be used as a promising nanodrug system in the cancer therapeutics.

DNA Aptamer Based Nanodrugs: Molecular Engineering for Efficiency.

In the past two decades, the study of cancer therapy has gradually advanced to the "nano" era. Numerous novel nanomaterials armed with unique physical properties have been introduced into biomedical research. At the same time, functional nucleic acid molecules, especially aptamers, have aroused broad attention from the biomedical community. Benefiting from the advancement of molecular engineering strategies, it is now feasible to combine the cancer-specific recognition capability of aptamers with various other special functions of nanomaterials to develop cancer-specific drugs at the nanoscale. Nanodrugs are now offering an unprecedented opportunity to achieve the goal of efficient targeted delivery as well as controlled release. This review highlights some achievements made in multiple aptamer-based nanodrug systems that have emerged in recent years, including studies in the infant stage of "proof-of-concept".

A cell-targeted, size-photocontrollable, nuclear-uptake nanodrug delivery system for drug-resistant cancer therapy.

The development of multidrug resistance (MDR) has become an increasingly serious problem in cancer therapy. The cell-membrane overexpression of P-glycoprotein (P-gp), which can actively efflux various anticancer drugs from the cell, is a major mechanism of MDR. Nuclear-uptake nanodrug delivery systems, which enable intranuclear release of anticancer drugs, are expected to address this challenge by bypassing P-gp. However, before entering the nucleus, the nanocarrier must pass through the cell membrane, necessitating coordination between intracellular and intranuclear delivery. To accommodate this requirement, we have used DNA self-assembly to develop a nuclear-uptake nanodrug system carried by a cell-targeted near-infrared (NIR)-responsive nanotruck for drug-resistant cancer therapy. Via DNA hybridization, small drug-loaded gold nanoparticles (termed nanodrugs) can self-assemble onto the side face of a silver–gold nanorod (NR, termed nanotruck) whose end faces were modified with a cell type-specific internalizing aptamer. By using this size-photocontrollable nanodrug delivery system, anticancer drugs can be efficiently accumulated in the nuclei to effectively kill the cancer cells.