Release Of Drug Doxorubicin Research Articles

Impact of Dendrimer Surface Functional Groups on the Release of Doxorubicin from Dendrimer Carriers

Generation 5 (G5) poly(amidoamine) dendrimers with acetyl (G5.NHAc), glycidol hydroxyl (G5.NGlyOH), and succinamic acid (G5.SAH) terminal groups were used to physically encapsulate an anticancer drug doxorubicin (DOX). Both UV-vis spectroscopy and multiple NMR techniques including one-dimensional NMR and two-dimensional NMR were applied to investigate the interactions between different dendrimers and DOX. The influence of the surface functional groups of G5 dendrimers on the DOX encapsulation, release kinetics, and cancer cell inhibition effect was investigated. We show that all three types of dendrimers are able to effectively encapsulate DOX and display therapeutic inhibition effect to cancer cells, which is solely associated with the loaded DOX. The relatively stronger interactions of G5.NHAc or G5.NGlyOH dendrimers with DOX than that of G5.SAH dendrimers with DOX demonstrated by NMR techniques correlate well with the slow release rate of DOX from G5.NHAc/DOX or G5.NGlyOH/DOX complexes. In contrast, the demonstrated weak interaction between G5.SAH and DOX causes a fast release of DOX, suggesting that the G5.SAH/DOX complex may not be a proper option for further in vivo research. Our findings suggest that the dendrimer surface functional groups are crucial for further design of multifunctional dendrimer-based drug delivery systems for various biomedical applications.

PH-sensitive polycarbonate micelles for enhanced intracellular release of anticancer drugs: a strategy to circumvent multidrug resistance

In this study, we have synthesized two novel amphiphilic diblock copolymers with aldehyde groups via organocatalytic ROP of a functionalized cyclic carbonate monomer (MTC-Bz) using polyethylene oxide (PEG) as the macroinitiator. The polymers were covalently conjugated with an anti-tumor drug doxorubicin (DOX) via a pH-sensitive Schiff-base linkage. The resulting conjugates formed micelles in phosphate-buffered saline (PBS) (pH 7.4) with an average size of about 100 nm and narrow size distribution. The surface charge of the micelles was close to zero. The micelles were stable in both PBS and cell culture media containing 10% FBS up to 5 days. The results obtained from the in vitro release study indicated that DOX release from the micelles was pH-dependent, being faster at pH 5.0 (the endolysosomal environment) than pH 7.4 (the extracellular environment). Human breast cancer MCF-7 cells and DOX-resistant MCF-7/Adr cells were employed to investigate the cellular uptake and cytotoxicity of DOX-loaded micelles. The confocal microscopy and flow cytometry studies showed that the uptake of DOX-loaded micelles by MCF-7 cells was similar to that of free DOX. In sharp contrast, the uptake of DOX-loaded micelles by MCF-7/Adr cells was significantly higher than that of free DOX. The polymers showed no toxicity to MCF-7 and MCF-7/Adr cells. The DOX-loaded micelles killed the cells efficiently. In particular, they were more potent against drug-resistant MCF-7/Adr cells than free DOX due to the higher cellular drug accumulation and pH-triggered intracellular drug release, providing a strategy to navigate around drug resistance. These DOX-conjugated micelles can be a promising carrier for the delivery of anticancer drugs with amine functional groups.

Drug release of pH-sensitive poly(l-aspartate)-b-poly(ethylene glycol) micelles with POSS cores

Amphiphilic poly(L-aspartate)-b-poly(ethylene glycol) block copolymers were synthesized and immobilized on polyhedral oligomeric silsesquioxanes (POSS) to obtain star shaped copolymers. 1-(3-Aminopropyl) imidazole was conjugated to the pendant groups of poly(L-aspartate) segments to fabricate pH-sensitive micelles. The anticancer drug doxorubicin (DOX) was trapped in the micelles to investigate the effects of side groups on the drug release behaviors. The mean diameters of DOX loaded micelles were around 50–60 nm, which were much smaller than those of blank micelles (100–200 nm). Both the drug loading content and encapsulation efficiency of the micelles decreased with the sequence of the side group substitution of carboxyl, benzyl and imidazole. The release of DOX loaded micelles with imidazole groups was pH-dependent, and more than 90% of the loaded DOX could be released within 48 hours in a weak acidic medium (pH 5.0). The flow cytometry and confocal laser scanning microscopy results revealed that the pH-sensitive micelles exhibited better anticancer activity.

Folic acid-modified laponite nanodisks for targeted anticancer drug delivery.

We report here an effective approach to modifying laponite (LAP) nanodisks with folic acid (FA) for targeted anticancer drug delivery applications. In this approach, LAP nanodisks were first modified with 3-aminopropyldimethylethoxysilane (APMES) to render them with abundant surface amines, followed by conjugation with FA via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) chemistry. The formed FA-modified LAP nanodisks (LM-FA) were then used to encapsulate anticancer drug doxorubicin (DOX). The surface modification of LAP nanodisks and the subsequent drug encapsulation within the LAP nanodisks were characterized via different techniques. We show that the LM-FA is able to encapsulate DOX with an efficiency of 92.1 ± 2.2%, and the formed LM-FA/DOX complexes are able to release DOX in a pH-dependent manner with a higher DOX release rate under acidic pH conditions than under physiological pH conditions. The encapsulation of DOX within LM-FA does not compromise its therapeutic activity. Importantly, the formed LM-FA/DOX complexes are able to specifically target cancer cells overexpressing high-affinity FA receptors as confirmed via flow cytometric analysis and confocal microscopic observation, and exert specific therapeutic efficacy to the target cancer cells. The developed FA-modified LAP nanodisks may hold great promise to be used as an efficient nanoplatform for targeted delivery of different anticancer drugs.

Highly hemocompatible zwitterionic micelles stabilized by reversible cross-linkage for anti-cancer drug delivery

Both blood stability and intelligent-responsiveness after reaching the drug-targeting site are very important features to make desirable nano-drug vehicles (NDVs). Here, a highly nonfouling cross-linked micelle based on a copolymer composed of carboxybetaine methacrylate (CBMA) as hydrophilic segment and 2-(methacryloyloxy)ethyl lipoate (MAEL) as hydrophobic and cross-linked segment is reported. Furthermore, a simple method to evaluate the hemocompatibility of NDVs through examining the activation of a blood-clotting protein (fibrinogen) was introduced. The micelles can encapsulate anticancer drug doxorubicin (DOX) conveniently and release DOX quickly in response to an intracellular reductive environment. With the advantages of excellent stability in fibrinogen (1mg/mL) PBS solution and 50% fetal bovine serum (FBS), and accelerated intracellular drug release, the biocompatible zwitterionic micelles stabilized by reversible cross-linkage might be a promising drug carrier for cancer chemotherapy.

In Vitro and In Vivo Imaging of Peptide-Encapsulated Polymer Nanoparticles for Cancer Biomarker Activated Drug Delivery

Gelatin nanoparticles coated with Cathepsin D-specific peptides were developed as a vehicle for the targeted delivery of the cancer drug doxorubicin (DOX) to treat breast malignancy. Cathepsin D, a breast cancer cell secretion enzyme, triggered the release of DOX by digesting the protective peptide-coating layer of nanoparticles. Fabricated nanoparticles were successfully detected with ultrasound imaging in both in vitro conditions and in vivo mouse cancer models. Cell viability experiments were conducted to determine the efficacy of biomarker activation specific to breast cancer cell lines. These experimental results were compared with the outcome of a viability experiment conducted on noncancerous cells. Viability decreased in human MCF7 mammary adenocarcinoma and mouse 4T1 mammary carcinoma cells, while that of noncancerous 3T3 fibroblast cells remained unaffected. Next, a real-time video of nanoparticle flow in mouse models was obtained using in vivo ultrasound imaging. The fluorescent profile of DOX was used as a means to examine nanoparticle localization in vivo. Results show the distribution of nanoparticles concentrated primarily within bladder and tumor sites of subject mice bodies. These findings support the use of biomarker coated nanoparticles in target specific therapy for breast cancer treatment.

Brush‐first and Click: Efficient Synthesis of Nanoparticles that Degrade and Release Doxorubicin in Response to Light

New strategies for the synthesis of multifunctional particles that respond to external stimuli and release biologically relevant agents will enable the discovery of new formulations for drug delivery. In this article, we combine two powerful methods: brush-first ring-opening metathesis polymerization and copper-catalyzed azide-alkyne cycloaddition click chemistry, for the synthesis of a novel class of brush-arm star polymers (BASPs) that simultaneously degrade and release the anticancer drug doxorubicin (DOX) in response to 365 nm light. In vitro cell viability studies were performed to study the toxicity of azide- and DOX-loaded BASPs. The former were completely nontoxic. The latter showed minimal toxicity in the absence of light; UV-triggered DOX release led to IC50 values that were similar to that of free DOX.

CuInS2 quantum dots/poly(l-glutamic acid)–drug conjugates for drug delivery and cell imaging

A new anticancer drug delivery system was developed based on the electrostatic complex of positively charged CuInS2 quantum dots (QDs) and negatively charged poly(l-glutamic acid) (PGA) conjugated with the model anticancer drug doxorubicin (DOX). Water-soluble near-infrared CuInS2 QDs capped with l-cysteine were directly synthesized by a hydrothermal method. DOX can quench the photoluminescence of CuInS2 QDs in QDs/PGA-DOX nanoparticles through a photoinduced electron transfer process, thus CuInS2 QDs are in the fluorescence "turn-off" state. After the QDs/PGA-DOX nanoparticles are exposed to carboxypeptidase or are taken up by cancer cells, PGA is hydrolysed to release DOX, inducing activation of the CuInS2 QDs fluorescence to the "turn-on" state. The QDs/PGA-DOX nanoparticles can deliver DOX to targeted cancer cells and monitor the DOX release based on the fluorescence "turn-on" signal of CuInS2 QDs, and this could be simultaneously used for the imaging of cancer cells. The multifunctional QDs/PGA-DOX nanoparticles have great potential in terms of their clinical application for cancer therapy.

Biodegradable Stereocomplex Micelles Based on Dextran-block-polylactide as Efficient Drug Deliveries

Biodegradable stereocomplex micelles (SCMs) based on amphiphilic dextran-block-polylactide (Dex-b-PLA) were designed and used for efficient intracellular drug deliveries. The Dex-b-PLA copolymers were successfully synthesized by click reaction. The structures of the resultant copolymers were verified by (1)H NMR and FT-IR spectra. The formation of stable micelles through self-assembly driven by the stereocomplexation between enantiomeric l- and d-PLA blocks was characterized by transmission electron microscopy (TEM), dynamic laser scattering (DLS), and fluorescence techniques. It was interesting to observe that the SCMs showed lower critical micelle concentration values (CMCs) because of the stereocomplex interaction between PLLA and PDLA. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis provided information on the thermal and crystal properties of the copolymers and SCMs. The improved stability of SCMs should be attractive for intracellular drug delivery. Thus, a model anticancer drug doxorubicin (DOX) was loaded into micelles, and the in vitro drug release in was also studied. The release kinetics of DOX showed DOX-loaded SCMs exhibited slower DOX release. Confocal laser scanning microscopy (CLSM) and flow cytometry studies also showed that the DOX-loaded SCMs exhibited a slower drug release behavior. Meanwhile, the MTT assay demonstrated that DOX-loaded SCMs show lower cellular proliferation inhibition against HepG2. In sum, the micelles through self-assembly driven by stereocomplex interaction would have great potential to be used as stable delivery vehicles for pharmaceutical and biomedical applications.

Synthesis of Polymer–Lipid Nanoparticles for Image-Guided Delivery of Dual Modality Therapy

For advanced treatment of diseases such as cancer, multicomponent, multifunctional nanoparticles hold great promise. In the current study we report the synthesis of a complex nanoparticle (NP) system with dual drug loading as well as diagnostic properties. To that aim we present a methodology where chemically modified poly(lactic-co-glycolic) acid (PLGA) polymer is formulated into a polymer-lipid NP that contains a cytotoxic drug doxorubicin (DOX) in the polymeric core and an anti-angiogenic drug sorafenib (SRF) in the lipidic corona. The NP core also contains gold nanocrystals (AuNCs) for imaging purposes and cyclodextrin molecules to maximize the DOX encapsulation in the NP core. In addition, a near-infrared (NIR) Cy7 dye was incorporated in the coating. To fabricate the NP we used a microfluidics-based technique that offers unique NP synthesis conditions, which allowed for encapsulation and fine-tuning of optimal ratios of all the NP components. NP phantoms could be visualized with computed tomography (CT) and near-infrared (NIR) fluorescence imaging. We observed timed release of the encapsulated drugs, with fast release of the corona drug SRF and delayed release of a core drug DOX. In tumor bearing mice intravenously administered NPs were found to accumulate at the tumor site by fluorescence imaging.

Green Synthetic, Multifunctional Hybrid Micelles with Shell Embedded Magnetic Nanoparticles for Theranostic Applications

The objective of this study is to design and develop a green-synthetic, multifunctional hybrid micelles with shell embedded magnetic nanoparticles for theranostic applications. The hybrid micelles were engineered based on complex micelles self-assembled from amphiphilic block copolymers Pluronic F127 and peptide-amphiphile (PA) pal-AAAAHHHD. The reason to choose PA is due to its amphiphilic character and the coordination capability for Fe(3+) and Fe(2+). The PA incorporation allows the in situ growth of the magnetic iron oxide nanoparticles onto the complex micelles, to yield the nanostructures with shell embedded magnetic nanoparticles at an ambient condition without any organic solvents. The anticancer drug doxorubicin (DOX) can be efficiently loaded into the hybrid micelles. Interestingly, the magnetic nanoparticles anchored on the shell were found to significantly retard the DOX release behavior of the drug loaded hybrid micelles. It was proposed that a cross-linking effect of the shell by magnetic nanoparticles is a key to underlie the above intriguing phenomenon, which could enhance the stability and control the drug diffusion of the hybrid micelles. Importantly, in vitro and in vivo magnetic resonance imaging (MRI) revealed the potential of these hybrid micelles to be served as a T2-weighted MR imaging contrast enhancer for clinical diagnosis.

Fabrication and characterization of a triple functionalization of graphene oxide with Fe3O4, folic acid and doxorubicin as dual-targeted drug nanocarrier

A novel triple functionalized drug delivery system was synthesized by encapsulation of superparamagnetic graphene oxide (GO) and doxorubicin (DOX) with folic acid (FA) conjugated chitosan (CHI). The carrier exhibited a high loading efficiency (0.98mg/mg), a high saturation magnetization (10.5emu/g) and a prolonged release rate. A real-time monitoring method on the drug release from graphene oxide (GO) was reported using DOX as the model drug. The release mechanism of DOX at different pH was investigated via monitoring the time dependency of the accumulative drug release. Results show that the drug release of DOX was pH sensitive as observed at pH 5.3 and pH 7.4 PBS solutions, the lower pH values lead to weaker hydrogen bonds and degradation of CHI, and thus result in a higher release rate of DOX. Especially, this system could be applied as a dual-targeted drug nanocarrier by combined biological (active) and magnetical (passive) targeting capabilities. Our research suggests that a novel triple functionalized, pH-responsive nanocarrier for anticancer drug has been synthesized.

A reduction-sensitive carrier system using mesoporous silica nanospheres with biodegradable polyester as caps

Mesoporous silica nanoparticles (MSN)-polymer hybrid combined with the aliphatic biodegradable polyester caps on the surface were first developed in order to manipulate the smart intracellular release of anticancer drugs. First, poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-PCL) was successfully grafted on the surface of MSN via disulfide bonds which could cleave under a reduction environment in tumor cells. The anticancer drug doxorubicin (DOX) was encapsulated into the particle pores. The in vitro drug release profile showed that DOX release was significantly restricted by the polymer caps at pH 7.4, while it was greatly accelerated upon the addition of GSH. Cytotoxicity evaluation showed good biocompatibility with the hybrid particles. Fast endocytosis and intracellular DOX release were observed by confocal laser scanning microscopy (CLSM). The DOX-loaded particles exhibited comparable antitumor activity with free DOX towards HeLa cells and showed in a time-dependent manner. This work developed an extensive method of utilizing aliphatic biodegradable polyesters as polymer caps for MSN to control drug delivery. The paper might offer a potential option for cancer therapy.

A pH-Sensitive, Biobased Calcium Carbonate Aragonite Nanocrystal as a Novel Anticancer Delivery System

The synthesised biobased calcium carbonate nanocrystals had demonstrated to be an effective carrier for delivery of anticancer drug doxorubicin (DOX). The use of these nanocrystals displayed high levels of selectivity and specificity in achieving effective cancer cell death without nonspecific toxicity. These results confirmed that DOX was intercalated into calcium carbonate nanocrystals at high loading and encapsulation efficiency (4.8 and 96%, resp.). The CaCO3/DOX nanocrystals are relatively stable at neutral pH (7.4), resulting in slow release, but the nanocrystals progressively dissociated in acidic pH (4.8) regimes, triggering faster release of DOX. The CaCO3/DOX nanocrystals exhibited high uptake by MDA MB231 breast cancer cells and a promising potential delivery of DOX to target cells. In vitro chemosensitivity using MTT, modified neutral red/trypan blue assay, and LDH on MDA MB231 breast cancer cells revealed that CaCO3/DOX nanocrystals are more sensitive and gave a greater reduction in cell growth than free DOX. Our findings suggest that CaCO3 nanocrystals hold tremendous promise in the areas of controlled drug delivery and targeted cancer therapy.

Fabrication of novel coumarin derivative functionalized polypseudorotaxane micelles for drug delivery

The fabrication and drug delivery of novel polypseudorotaxane micelles with small molecule coumarin derivative as hydrophobic segment were reported. 7-Carboxymethoxy coumarin was immobilized on the terminal hydroxyl groups of poly(ethylene glycol) (PEG). The modified PEG chains were threaded in α-cyclodextrins (α-CDs) to form polypseudorotaxanes. The polypseudorotaxanes self-assembled into supramolecular micelles driven by hydrophobic interaction and polypseudorotaxane crystallization. Anti-tumor drug doxorubicin (DOX) was trapped in the micelles. The structure, morphology, drug release profile and cytotoxicity of the micelles were investigated. The in vitro anti-tumor studies including cellular uptake and inhibition efficiency were performed on mice cancer cell lines of TC1 lung cancer cells and B16 melanoma cells. The results revealed that the 7-carboxymethoxy coumarin modified PEG could thread into the cavity of α-CDs to form necklace-like polypseudorotaxanes. The polypseudorotaxanes self-assembled into spherical micelles with the mean size of 30 nanometers, and the size was increased to about 80 nanometers after the drug was loaded. The drug loading content of the micelles was decreased with increasing the chain length of PEG. The sustaining release of DOX could last for 32 hours. The polypseudorotaxane micelles were non-toxic to both TC1 and B16 cells. The IC50 of the DOX loaded polypseudorotaxane micelles with PEG2k was lower than that of micelles with PEG4k or PEG6k both in TC1 and B16 cells.

Supramolecular amphiphilic multiarm hyperbranched copolymer: synthesis, self-assembly and drug delivery applications

Novel supramolecular amphiphilic multiarm hyperbranched copolymers were successfully constructed through the molecular recognition of nucleobases. First, adenine-terminated H40-star-poly(e-caprolactone)-adenine (H40-star-PCL-A) and uracil-terminated poly(ethylene glycol) (PEG-U) were successfully prepared. Due to the molecular recognition between A and U moieties, supramolecular multiarm hyperbranched copolymers were obtained by simply mixing the hydrophobic H40-star-PCL-A core and hydrophilic PEG-U shell. They not only had similar properties to conventional covalent-linked multiarm hyperbranched copolymers, but also possessed a dynamic and tunable nature. These supramolecular hyperbranched copolymers were found to self-assemble into pH-responsive micelles with low critical micelle concentration (CMC) because of non-covalent connection and hyperbranched architecture. The size of the self-assembled micelles could be easily tailored by changing the ratio of hydrophobic H40-star-PCL-A core and hydrophilic PEG-U arm. Moreover, encapsulation and controlled drug release were demonstrated with the chemotherapeutic drug doxorubicin (DOX). These supramolecular hyperbranched copolymer systems represent an evolution over conventional stimuli-responsive covalent-bonded hyperbranched copolymer systems and display a significant reduction in the viability of HeLa cells upon triggered release of DOX from the supramolecular micelles.

Accelerated killing of cancer cells using a multifunctional single-walled carbon nanotube-based system for targeted drug delivery in combination with photothermal therapy.

The photothermal effect of single-walled carbon nanotubes (SWCNTs) in combination with the anticancer drug doxorubicin (DOX) for targeting and accelerated destruction of breast cancer cells is demonstrated in this paper. A targeted drug-delivery system was developed for selective killing of breast cancer cells with polyethylene glycol biofunctionalized and DOX-loaded SWCNTs conjugated with folic acid. In our work, in vitro drug-release studies showed that the drug (DOX) binds at physiological pH (pH 7.4) and is released only at a lower pH, ie, lysosomal pH (pH 4.0), which is the characteristic pH of the tumor environment. A sustained release of DOX from the SWCNTs was observed for a period of 3 days. SWCNTs have strong optical absorbance in the near-infrared (NIR) region. In this special spectral window, biological systems are highly transparent. Our study reports that under laser irradiation at 800 nm, SWCNTs exhibited strong light–heat transfer characteristics. These optical properties of SWCNTs open the way for selective photothermal ablation in cancer therapy. It was also observed that internalization and uptake of folate-conjugated NTs into cancer cells was achieved by a receptor-mediated endocytosis mechanism. Results of the in vitro experiments show that laser was effective in destroying the cancer cells, while sparing the normal cells. When the above laser effect was combined with DOX-conjugated SWCNTs, we found enhanced and accelerated killing of breast cancer cells. Thus, this nanodrug-delivery system, consisting of laser, drug, and SWCNTs, looks to be a promising selective modality with high treatment efficacy and low side effects for cancer therapy.

Antitumor efficacy of doxorubicin-loaded electrospun nano-hydroxyapatite–poly(lactic-co-glycolic acid) composite nanofibers

Electrospun composite nanofibrous scaffolds have attracted much interest for use as drug delivery vehicles in recent years. Herein, we attempted to first encapsulate the anticancer drug doxorubicin (DOX) using inorganic rod-like nano-hydroxyapatite (n-HA) as a carrier. Then, the DOX-loaded n-HA particles were mixed with poly(lactic-co-glycolic acid) (PLGA) solution to fabricate electrospun hybrid nanofibers. The formation of drug–n-HA complexes and the drug-loaded composite nanofibers were characterized using different techniques. In vitro DOX release behavior was examined using UV-vis spectroscopy under both neutral and acidic conditions. The anticancer activity of the drug-loaded composite nanofibers was evaluated via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) viability assay and phase contrast microscopic morphology observation of a model KB cancer cell line (a human epithelial carcinoma cell line). We show that DOX can be successfully loaded onto the surface of the n-HA and the formed composite fibers have a uniform and continuous fibrous morphology. Importantly, the loaded DOX shows a sustained release profile, and the released DOX from the nanofibers displays non-compromised antitumor activity towards the growth inhibition of KB cells. With the significantly reduced burst release profile and the improved mechanical durability of the composite nanofiber system compared with n-HA-free PLGA nanofibers, the designed organic–inorganic hybrid nanofibers could be used as a versatile drug delivery system for encapsulation and sustained release of different drugs with prolonged therapeutic efficacy for different biomedical applications.

Multifunctional Chitosan Magnetic-Graphene (CMG) Nanoparticles: a Theranostic Platform for Tumor-targeted Co-delivery of Drugs, Genes and MRI Contrast Agents.

Combing chemotherapy with gene therapy has been one of the most promising strategies for the treatment of cancer. The noninvasive MRI with superparamagnetic iron oxide (SPIO) as contrast agent is one of the most effecitve techniques for evaluating the antitumor therapy. However, to construct a single system that can deliver efficiently gene, drug and SPIO to the cancer site remains a challenge. Herein, we report a chitosan functionalized magnetic graphene nanoparticle (CMG) platform for simultaneous gene/drug and SPIO delivery to tumor. The phantom and ex vivo MRI images suggest CMG as a strong T2 contrast-enhancing agent. The CMGs are biocompatible as evaluated by the WST assay and predominantly accumulate in tumors as shown by biodistribution studies and MRI. The anticancer drug doxorubicin (DOX) loaded CMGs (DOX-CMGs) release DOX faster at pH 5.1 than at pH 7.4, and more effective (IC50 = 2 μM) in killing A549 lung cancer cells than free DOX (IC50 = 4 μM). CMGs efficiently deliver DNA into A549 lung cancer cells and C42b prostate cancer cells. In addition, i.v. administration of GFP-plasmid encapsulated within DOX-CMGs into tumor-bearing mice has showed both GFP expression and DOX accumulation at the tumor site at 24 and 48 hrs after administration. These results indicate CMGs provide a robust and safe theranostic platform, which integrates targeted delivery of both gene medicine and chemotherapeutic drug(s), and enhanced MR imaging of tumors. The integrated chemo- and gene- therapeutic and diagnostic design of CMG nanoparticles shows promise for simultaneous targeted imaging, drug delivery and real -time monitoring of therapeutic effect for cancer.

Fabrication of polymeric micelles with core–shell–corona structure for applications in controlled drug release

Thermo-responsive polymeric micelles of poly (ethylene glycol)-b-poly(2-hydroxyethyl methacrylate-g-lactide)-b-poly(N-isopropylacrylamide) (PEG-P(HEMA-PLA)-PNIPAM) with core–shell–corona structure were fabricated for applications in controlled drug release. The graft copolymer of PEG-P(HEMA-PLA)-PNIPAM was self-assembled into core–shell micelles with a densely PLA core and mixed PEG/PNIPAM shells at 25 °C in aqueous media. By increasing the temperature above the lower critical solution temperature of PNIPAM, these core–shell micelles could be converted into core–shell–corona micelles because of the collapse of PNIPAM block on the PLA core as the inner shell and the soluble PEG block stretching outside as the outer corona. Anticancer drug doxorubicin (DOX) was loaded in the polymeric micelles as a model drug. Compared with polymeric micelles formed by liner PEG-b-PLA-b-PNIPAM triblock copolymer, these polymeric micelles exhibited higher loading capacity, and release of DOX from the polymeric micelles with core–shell–corona structure was well-controlled.