Nanomedicine Platform Research Articles

Nanostructured lipid carriers as multifunctional nanomedicine platform for pulmonary co-delivery of anticancer drugs and siRNA

We developed, synthesized, and tested a multifunctional nanostructured lipid nanocarrier-based system (NLCS) for efficient delivery of an anticancer drug and siRNA directly into the lungs by inhalation. The system contains: (1) nanostructured lipid carriers (NLC); (2) anticancer drug (doxorubicin or paclitaxel); (3) siRNA targeted to MRP1 mRNA as a suppressor of pump drug resistance; (4) siRNA targeted to BCL2 mRNA as a suppressor of nonpump cellular resistance and (5) a modified synthetic analog of luteinizing hormone-releasing hormone (LHRH) as a targeting moiety specific to the receptors that are overexpressed in the plasma membrane of lung cancer cells. The NLCS was tested in vitro using human lung cancer cells and in vivo utilizing mouse orthotopic model of human lung cancer. After inhalation, the proposed NLCS effectively delivered its payload into lung cancer cells leaving healthy lung tissues intact and also significantly decreasing the exposure of healthy organs when compared with intravenous injection. The NLCS showed enhanced antitumor activity when compared with intravenous treatment. The data obtained demonstrated high efficiency of proposed NLCS for tumor-targeted local delivery by inhalation of anticancer drugs and mixture of siRNAs specifically to lung cancer cells and, as a result, efficient suppression of tumor growth and prevention of adverse side effects on healthy organs.

Silver Nanoscale Antisense Drug Delivery System for Photoactivated Gene Silencing

The unique photophysical properties of noble metal nanoparticles contribute to their potential as photoactivated drug delivery vectors. Here we demonstrate the synthesis and characterization of 60-80 nm silver nanoparticles (SNPs) decorated with thiol-terminated photolabile DNA oligonucleotides. In vitro assays and fluorescent confocal microscopy of treated cell cultures show efficient UV-wavelength photoactivation of surface-tethered caged ISIS2302 antisense oligonucleotides possessing internal photocleavable linkers. As a demonstration of the advantages of these novel nanocarriers, we investigate properties including: enhanced stability to nucleases, increased hybridization activity upon photorelease, and efficient cellular uptake as compared to commercial transfection vectors. Their potential as multicomponent delivery agents for oligonucleotide therapeutics is shown through regulation of ICAM-1 (Intracellular Adhesion Molecule-1) silencing. Our results suggest a means to achieve light-triggered, spatiotemporally controlled gene silencing via nontoxic silver nanocarriers, which hold promise as tailorable platforms for nanomedicine, gene expression studies, and genetic therapies.

Imaging Inward and Outward Trafficking of Gold Nanoparticles in Whole Animals

Gold nanoparticles have emerged as novel safe and biocompatible tools for manifold applications, including biological imaging, clinical diagnostics, and therapeutics. The understanding of the mechanisms governing their interaction with living systems may help the design and development of new platforms for nanomedicine. Here we characterized the dynamics and kinetics of the events underlying the interaction of gold nanoparticles with a living organism, from the first interaction nanoparticle/cell membrane, to the intracellular trafficking and final extracellular clearance. By treating a simple water invertebrate (the cnidarian Hydra polyp) with functionalized gold nanoparticles, multiple inward and outward routes were imaged by ultrastructural analyses, including exosomes as novel undescribed carriers to shuttle the nanoparticles in and out the cells. From the time course imaging a highly dynamic picture emerged in which nanoparticles are rapidly internalized (from 30 min onward), recruited into vacuoles/endosome (24 h onward), which then fuse, compact and sort out the internalized material either to storage vacuoles or to late-endosome/lysosomes, determining almost complete clearance within 48 h from challenging. Beside classical routes, new portals of entry/exit were captured, including exosome-like structures as novel undescribed nanoparticle shuttles. The conservation of the endocytic/secretory machinery through evolution extends the value of our finding to mammalian systems providing dynamics and kinetics clues to take into account when designing nanomaterials to interface with biological entities.

A platelet-mimetic paradigm for metastasis-targeted nanomedicine platforms.

There is compelling evidence that, beyond their traditional role in hemostasis and thrombosis, platelets play a significant role in mediating hematologic mechanisms of tumor metastasis by directly and indirectly interacting with pro-metastatic cancer cells. With this rationale, we hypothesized that platelets can be an effective paradigm to develop nanomedicine platforms that utilize platelet-mimetic interaction mechanisms for targeted diagnosis and therapy of metastatic cancer cells. Here we report on our investigation of the development of nanoconstructs that interact with metastatic cancer cells via platelet-mimetic heteromultivalent ligand-receptor pathways. For our studies, pro-metastatic human breast cancer cell line MDA-MB-231 was studied for its surface expression of platelet-interactive receptors, in comparison to another low-metastatic human breast cancer cell line, MCF-7. Certain platelet-interactive receptors were found to be significantly overexpressed on the MDA-MB-231 cells, and these cells showed significantly enhanced binding interactions with active platelets compared to MCF-7 cells. Based upon these observations, two specific receptor interactions were selected, and corresponding ligands were engineered onto the surface of liposomes as model nanoconstructs, to enable platelet-mimetic binding to the cancer cells. Our model platelet-mimetic liposomal constructs showed enhanced targeting and attachment of MDA-MB-231 cells compared to the MCF-7 cells. These results demonstrate the promise of utilizing platelet-mimetic constructs in modifying nanovehicle constructs for metastasis-targeted drug as well as modifying surfaces for ex-vivo cell enrichment diagnostic technologies.

The synergistic effect and mechanism of doxorubicin-ZnO nanocomplexes as a multimodal agent integrating diverse anticancer therapeutics

BackgroundNanomaterials have emerged as ideal multimodal nanomedicine platforms, each one combining different designs and therapeutic approaches in a single system against cancer. The aim of the current study was to explore the synergistic effect and mechanism of a doxorubicin (Dox)-ZnO nanocomplex as a multimodal drug delivery system, integrating Dox chemotherapy and ZnO-mediated photodynamic therapy, in anticancer therapeutics.MethodsDox was loaded onto ZnO nanomaterials, forming complexes with the transition metal Zn to yield the Dox-ZnO nanocomplexes. After culture with SMMC-7721 hepatocarcinoma cells, the cellular uptake was quantitatively detected by flow cytometry and visualized by fluorescence microscopy. The synergistic effects of the different anticancer therapeutic modalities on the proliferation of SMMC-7721 hepatocarcinoma cells were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of B-cell lymphoma 2 protein (Bcl-2), Bcl-2 associated X protein (Bax), caspase 9, and caspase 3 were examined by Western blot, to elucidate the possible molecular mechanisms involved.ResultsOur observations demonstrated that Dox-ZnO nanocomplexes could act as an efficient drug delivery system for importing Dox into SMMC-7721 cells, enhancing its potential chemotherapy efficiency by increasing the intracellular concentration of Dox. With the addition of ultraviolet (UV) illumination, the ZnO nanomaterials showed excellent photodynamic therapeutic properties, attacking the cancer cells further. Thus the caspase-dependent apoptosis was synergistically induced, resulting in distinct improvement in anticancer activity.ConclusionThe Dox-ZnO nanocomplex presents a promising multimodal agent for comprehensive cancer treatment.

Sequential thermo-induced self-gelation and acid-triggered self-release process of drug-conjugated nanoparticles: a strategy for the sustained and controlled drug delivery to tumors.

A novel strategy was purposed to sustainedly deliver drug-loaded nanoparticles (NPs) to tumor sites and further enhance intracellular drug release. NPs with the ability of sequential self-gelation and self-release in response to a tumor-specific microenvironment were developed, which involved the conjugation of doxorubicin (DOX) on a thermosensitive amphiphilic copolymer (poly(ε-caprolactone)-b-poly(ethylene glycol)-b-poly(ε-caprolactone), PCEC) via acid-cleavable hydrazone linkages. The conjugate (PCEC-co-DOX) can self-assemble into micelle-like NPs in water. Moreover, the freeze-dried PCEC-co-DOX NP powder with good dispersibility in water can easily be constructed into an injectable NP aqueous dispersion at ambient temperature, making it convenient for storage and clinical applications. After injection, the dispersion can in situ thermosensitively self-gelate, anchoring large amounts of NPs at the tumor site. Subsequently, the formed NP self-supported gel can sustainedly release NPs themselves in an acidic tumor microenvironment. The released DOX-co-PCEC NPs were taken up by tumor cells and finally realized in intracellular drug release by the acid-triggered cleavage of the hydrazone bond. Compared with the repeated injection of free DOX, a single peritumoral injection of DOX-co-PCEC NP aqueous dispersion achieved a similar tumor inhibition effect but exhibited lower systemic toxicity. In vivo biodistribution studies indicated that DOX delivered by the DOX-co-PCEC NP hydrogel accumulated mainly in tumor tissue rather than in healthy tissue in mice treated with a single peritumoral injection. These results suggest that the design presented here provides a promising nanomedicine platform for cancer therapy.

Simultaneous Diagnosis and Gene Therapy of Immuno-Rejection in Rat Allogeneic Heart Transplantation Model Using a T-Cell-Targeted Theranostic Nanosystem

As the final life-saving treatment option for patients with terminal organ failure, organ transplantation is far from an ideal solution. The concomitant allograft rejection, which is hardly detectable especially in the early acute rejection (AR) period characterized by an intense cellular and humoral attack on donor tissue, greatly affects the graft survival and results in rapid graft loss. Based on a magnetic resonance imaging (MRI)-visible and T-cell-targeted multifunctional polymeric nanocarrier developed in our lab, effective co-delivery of pDNA and superparamagnetic iron oxide nanoparticles into primary T cells expressing CD3 molecular biomarker was confirmed in vitro. In the heart transplanted rat model, this multifunctional nanocarrier showed not only a high efficiency in detecting post-transplantation acute rejection but also a great ability to mediate gene transfection in T cells. Upon intravenous injection of this MRI-visible polyplex of nanocarrier and pDNA, T-cell gathering was detected at the endocardium of the transplanted heart as linear strongly hypointense areas on the MRI T(2)*-weighted images on the third day after cardiac transplantation. Systematic histological and molecular biology studies demonstrated that the immune response in heart transplanted rats was significantly suppressed upon gene therapy using the polyplex bearing the DGKα gene. More excitingly, the therapeutic efficacy was readily monitored by noninvasive MRI during the treatment process. Our results revealed the great potential of the multifunctional nanocarrier as a highly effective imaging tool for real-time and noninvasive monitoring and a powerful nanomedicine platform for gene therapy of AR with high efficiency.

Diamond as a nanomedical agent for versatile applications in drug delivery, imaging, and sensing

AbstractA spectrum of materials has been explored as potential platforms for nanomedicine in the areas of drug delivery, imaging, and diagnostics/sensing. Depending upon the application required, the therapeutic compound being delivered, or the imaging agent being modified, certain nanoparticulate materials offer specific advantages that may uniquely enhance efficiency. Among the classes of particles being investigated, diamond‐based platforms have emerged as promising vehicles for drug delivery and imaging following several recent studies that demonstrate their ability to enhance therapeutic efficacy, particularly for anthracyclines, mediate markedly improved magnetic resonance imaging contrast and photostable fluorescence, possess scalable processing parameters, and exhibit biocompatibility, among many other important attributes. More specifically, detonation NDs have faceted surfaces that can mediate potent interactions with surrounding water molecules or therapeutic compounds. This attribute can mitigate premature drug release to prevent major side effects such as myelosuppression, while water molecule recruitment can increase the relaxivity of covalently conjugated gadolinium. These properties of NDs and diamond‐based devices will be discussed in this article, with a focus on therapeutic delivery in addition to insight on their use in imaging, devices, implants/coatings, and biocompatibility. Key areas of potential, where advances in biology and medicine can be realized through the continued development of this platform as well as requisite future studies, will also be highlighted.

Mesoporous Silica Nanoparticles: Their Projection in Nanomedicine

Mesoporous silica nanoparticles are receiving growing attention by the scientific biomedical community. Among the different types of inorganic nanomaterials, mesoporous silica nanoparticles have emerged as promising multifunctional platforms for nanomedicine. Since their introduction in the drug delivery landscape in 2001, mesoporous materials for drug delivery are receiving growing scientific interest for their potential applications in the biotechnology and nanomedicine fields. The ceramic matrix efficiently protects entrapped guest molecules against enzymatic degradation or denaturation induced by pH and temperature as no swelling or porosity changes take place as a response to variations in the surrounding medium. It is possible to load huge amounts of cargo into the mesopore voids and capping the pore entrances with different nanogates. The application of a stimulus provokes the nanocap removal and triggers the departure of the cargo. This strategy permits the design of stimuli-responsive drug delivery nanodevices.

Multifunctional Nanomedicine Platforms for Cancer Therapy

Biocompatible nanomaterials have emerged as ideal platforms to develop multi-functionalization for achieving a compound effect using one system in which each component has a specially designed function. In this context, this article reviews multifunctional nanomedicine platforms for cancer therapy. The paper describes different types of multifunctional nanomedicine platforms, mainly co-delivery of drugs/genes in a single formulation for synergistic anticancer effect, specific strategies for targeting cancer therapy, smart control released drug delivery systems responding to certain internal or external stimuli, paradigms for theranostics to monitor effects in real time, and combination drug with thermal, sound, and light energies mediating multi-mode cancer treatment. Multifunctional nanomedicine platforms with different designs and therapeutic approaches for cancer and their translation from bench to bedside offer promising opportunities to benefit patients in the future.

Biomedical nanomaterials for imaging-guided cancer therapy

To date, even though various kinds of nanomaterials have been evaluated over the years in order to develop effective cancer therapy, there is still significant challenges in the improvement of the capabilities of nano-carriers. Developing a new theranostic nanomedicine platform for imaging-guided, visualized cancer therapy is currently a promising way to enhance therapeutic efficiency and reduce side effects. Firstly, conventional imaging technologies are reviewed with their advantages and disadvantages, respectively. Then, advanced biomedical materials for multimodal imaging are illustrated in detail, including representative examples for various dual-modalities and triple-modalities. Besides conventional cancer treatment (chemotherapy, radiotherapy), current biomaterials are also summarized for novel cancer therapy based on hyperthermia, photothermal, photodynamic effects, and clinical imaging-guided surgery. In conclusion, biomedical materials for imaging-guided therapy are becoming one of the mainstream treatments for cancer in the future. It is hoped that this review might provide new impetus to understand nanotechnology and nanomaterials employed for imaging-guided cancer therapy.

Grand Challenges in Modulating The Immune Response with RNAi Nanomedicines

RNAi is a ubiquitous and highly specific, endogenous, evolutionarily conserved mechanism of gene silencing. RNAi holds great promise as a novel therapeutic modality. Despite the rapid progress in the understanding and utilization of RNAi in vitro, the application of RNAi in vivo has been met with great difficulties, mainly in the delivery of these molecules into specific cell types. Here, we describe the major systemic nanomedicine platforms that have been developed. Focus is given to the development of new strategies to target subsets of leukocytes, which are among the most difficult cells to transduce with RNAi. Finally, we discuss the hurdles and potential opportunities for in vivo manipulation of the immune response utilizing RNAi nanomedicines.

Sonoproduction of Liposomes and Protein Particles as Templates for Delivery Purposes

The development of nano and micro delivery systems (DS), so small in size, is growing in importance, such as in drug targeting. In an era where nano is the new trend, micro and nano materials are in the forefront of progress. These systems can be produced by a diversity of methods. However, the use of high-intensity ultrasound offers an easy and versatile tool for nano- and microstructured materials that are often unavailable by conventional methods. Similarly to the synthesis methods that can be used, several starting materials can be applied to produce particulate systems. In this review, the recent strategic development of DS is discussed with emphasis on liposomes and polymer-based, specially protein-based, nanomedicine platforms for drug delivery. Among the variety of applications that materials in the particulate form can have, the control release of drugs is probably the most prominent one, as these have been in the forefront line of interest for biomedical applications. The basic concepts of sonochemical process pertaining to DS are summarized as well as the role of sonochemical procedure to their preparation. The different applications of these systems wrap up this review.

Liposomes: From a Clinically Established Drug Delivery System to a Nanoparticle Platform for Theranostic Nanomedicine

For decades, clinicians have used liposomes, self-assembled lipid vesicles, as nanoscale systems to deliver encapsulated anthracycline molecules for cancer treatment. The more recent proposition to combine liposomes with nanoparticles remains at the preclinical development stages; however, such hybrid constructs present great opportunities to engineer theranostic nanoscale delivery systems, which can combine simultaneous therapeutic and imaging functions. Many novel nanoparticles of varying chemical compositions are being developed in nanotechnology laboratories, but further chemical modification is often required to make these structures compatible with the biological milieu in vitro and in vivo. Such nanoparticles have shown promise as diagnostic and therapeutic tools and generally offer a large surface area that allows covalent and non-covalent surface functionalization with hydrophilic polymers, therapeutic moieties, and targeting ligands. In most cases, such surface manipulation diminishes the theranostic properties of nanoparticles and makes them less stable. From our perspective, liposomes offer structural features that can make nanoparticles biocompatible and present a clinically proven, versatile platform for further enhancement of the pharmacological and diagnostic efficacy of nanoparticles. In this Account, we describe two examples of liposome-nanoparticle hybrids developed as theranostics: liposome-quantum dot hybrids loaded with a cytotoxic drug (doxorubicin) and artificially enveloped adenoviruses. We incorporated quantum dots into lipid bilayers, which rendered them dispersible in physiological conditions. This overall vesicular structure allowed them to be loaded with doxorubicin molecules. These structures exhibited cytotoxic activity and labeled cells both in vitro and in vivo. In an alternative design, lipid bilayers assembled around non-enveloped viral nanoparticles and altered their infection tropism in vitro and in vivo with no chemical or genetic capsid modifications. Overall, we have attempted to illustrate how alternative strategies to incorporate nanoparticles into liposomal nanostructures can overcome some of the shortcomings of nanoparticles. Such hybrid structures could offer diagnostic and therapeutic combinations suitable for biomedical and even clinical applications.

Nanoscale Metal–Organic Frameworks for Biomedical Imaging and Drug Delivery

Metal-organic frameworks (MOFs), a class of hybrid materials formed by the self-assembly of polydentate bridging ligands and metal-connecting points, have been studied for a variety of applications. Recently, these materials have been scaled down to nanometer sizes, and this Account details the development of nanoscale metal-organic frameworks (NMOFs) for biomedical applications. NMOFs possess several potential advantages over conventional nanomedicines such as their structural and chemical diversity, their high loading capacity, and their intrinsic biodegradability. Under relatively mild conditions, NMOFs can be obtained as either crystalline or amorphous materials. The particle composition, size, and morphology can be easily tuned to optimize the final particle properties. Researchers have employed two general strategies to deliver active agents using NMOFs: by incorporating active agents into the frameworks or by loading active agents into the pores and channels of the NMOFs. The modification of NMOF surfaces with either silica coatings or organic polymers improves NMOF stability, fine-tunes their properties, and imparts additional functionality. Preliminary biomedical applications of NMOFs have focused on their use as delivery vehicles for imaging contrast agents and molecular therapeutics. Because NMOFs can carry large amounts of paramagnetic metal ions, they have been extensively explored as magnetic resonance imaging (MRI) contrast agents. Both Gd(3+)- and Mn(2+)-containing NMOFs have shown excellent efficacy as T(1)-weighted contrast agents with large per metal- and per particle-based MR relaxivities. Fe(3+)-containing NMOFs have demonstrated excellent T(2)-weighted contrast enhancement. Upon intravenous injection of iron carboxylate NMOFs in Wistar rats, researchers observed negative signal enhancement in the liver and spleen, which dissipated over time, indicating the degradation and clearance of the NMOF. Through the incorporation of luminescent or high Z element building blocks, NMOFs have also served as viable contrast agents for optical imaging or X-ray computed tomography (CT) imaging. Incorporation of membrane impermeable dyes into NMOFs allowed for their uptake by cancer cells and for their controlled release as the framework decomposed. NMOFs have been used to deliver anticancer drugs and other chemotherapeutics. Cisplatin prodrugs were incorporated within NMOFs at exceptionally high levels, either through use of the prodrug as the building block or through attachment of the prodrug onto the framework after synthesis. These NMOFs were encapsulated within a silica shell and targeted to cancer cells. In vitro assays revealed that the targeted NMOFs possessed similar efficacy to cisplatin, while the nontargeted NMOFs were less active. Several different therapeutic molecules were loaded within porous iron-carboxylate NMOFs at unprecedented levels. The NMOF showed sustained drug release with no burst effect, and in vitro assays revealed that the nanoencapsulated drug possessed similar efficacy to the free drug. Although still at a very early stage of development, NMOFs have already shown great promise as a novel platform for nanomedicine. The compositional tunability and mild synthetic conditions used to produce NMOFs should allow for the incorporation of other imaging and therapeutic agents and their effective delivery to targeted cells in vivo.

Nanomaterials for cancer therapy and imaging.

A variety of organic and inorganic nanomaterials with dimensions below several hundred nanometers are recently emerging as promising tools for cancer therapeutic and diagnostic applications due to their unique characteristics of passive tumor targeting. A wide range of nanomedicine platforms such as polymeric micelles, liposomes, dendrimers, and polymeric nanoparticles have been extensively explored for targeted delivery of anti-cancer agents, because they can accumulate in the solid tumor site via leaky tumor vascular structures, thereby selectively delivering therapeutic payloads into the desired tumor tissue. In recent years, nanoscale delivery vehicles for small interfering RNA (siRNA) have been also developed as effective therapeutic approaches to treat cancer. Furthermore, rationally designed multi-functional surface modification of these nanomaterials with cancer targeting moieties, protective polymers, and imaging agents can lead to fabrication versatile theragnostic nanosystems that allow simultaneous cancer therapy and diagnosis. This review highlights the current state and future prospects of diverse biomedical nanomaterials for cancer therapy and imaging.

Nanomedical Platform for Drug Delivery

Nanoparticles hold tremendous potential as an effective drug delivery system. The developments in nanotechnology for drug delivery laid platform for nanomedicine. To achieve efficient drug delivery it is important to understand the interactions of nanomaterials with the biological environment. This rapidly growing field allows cross-disciplinary researchers the opportunity to design and develop multifunctional nanoparticles in the form of nanotubes that can target, diagnose, and treat diseases such as cancer. Here I discussed about the engineering of nanotubes which targets drug delivery, barriers of drug delivery and advanced drug delivery systems.

Apoferritin-based nanomedicine platform for drug delivery: equilibrium binding study of daunomycin with DNA

This paper describes the preparation and optimization of the analytical properties of the protein based drug delivery platform apoferritin. In biological systems, the protein cage ferritin is used to store iron and to keep it from building to toxic levels in cells. When the iron atoms are removed from ferritin, apoferritin is formed. In this study, daunomycin, an anthracycline antibiotic drug that has been used for specific types of cancer treatment such as acute myeloid leukemia and acute lymphocytic leukemia, was encapsulated within the protein cage for drug delivery. Daunomycin slows or stops the growth of cancer cells by binding with the cell's DNA. The model for daunomycin-DNA complex binding mechanism is intercalation, where daunomycin binds with approximately every 3 base pairs causing a local unwinding, but a negligible distortion of the helical conformation. The binding affinity for free DNA is higher than that of structured DNA in cells. Upon binding with DNA the fluorescence intensity of daunomycin decreases. We used apoferritin's ability to disassemble and reassemble under pH control to load the therapeutic compound daunomycin. The combination of a modifiable interior and exterior surface and the passable hydrophobic and hydrophilic channels through the cage allows the containment or attachment of both insoluble and soluble drugs for delivery. At experimental pH 5 conditions the interaction between the apoferritin interior cage and daunomycin is weak making it difficult to encapsulate the drug effectively within the protein cage. The incorporation of poly-L-aspartic acid (PLAA), a polypeptide and biodegradable material that does not increase the toxicity of the drug delivery system and is negatively charged at pH 5.0, into the drug delivery system resulted in a substantial improvement in the drug encapsulation. The binding properties of free daunomycin with DNA were compared to the newly synthesized apoferritin protein based drug delivery system. Encapsulation of the daunomycin within the apoferritin protein cage had little effect upon the intrinsic binding constant, Ki, or the exclusion parameter n as compared to the free daunomycin model. The study resulted in the design and optimization of a unique protein based drug delivery platform using the protein cage apoferritin for potential therapeutic administration of the anti-cancer agent daunomycin.

A pH-sensitive polymeric nanovesicle based on biodegradable poly(ethylene glycol)-b-poly(2-(diisopropylamino)ethyl aspartate) as a MRI-visible drug delivery system

Diblock copolymers of poly(ethylene glycol) (PEG) and biodegradable 2-(diisopropylamino)ethanol grafted poly(L-aspartic acid) (PAsp(DIP)) were synthesized and evaluated as a MRI-visible and pH-sensitive drug delivery system. The copolymers can self-assemble into stable vesicles in aqueous solutions at neutral pH, resembling the physiological environment, whereas they disassemble in acidic endosomal/lysosomal compartments of tumor cells to achieve rapid drug release. The anticancer drug doxorubicin (DOX) and hydrophilic superparamagnetic iron oxide nanoparticles (SPIONs) were encapsulated inside the inner aqueous core of the vesicles for cancer therapy and MR imaging, respectively. In vitrodrug release studies showed that the DOX release from the pH-sensitive vesicles was significantly faster at pH 5.0 than at pH 7.4. SPIONs clustering inside the inner aqueous core of the vesicles resulted in a high spin–spin (T2) relaxivity. Cell culture studies showed that the DOX-SPION-loaded vesicles could be effectively internalized by human hepatic cancer Bel 7402 cells, and DOX could be rapidly released from vesicles inside lysosomal compartments and then migrated into nuclei. Consequently effective suppression of cancer cell growth was detected. This study demonstrated the potential of the biodegradable DOX-SPION-loaded pH-sensitive vesicles as an effective multifunctional nanomedicine platform for cancer therapy due to their pH-triggerable drug release and high MRI sensitivity.

Multifunctional Nanomedicine Platform for Cancer Specific Delivery of siRNA by Superparamagnetic Iron Oxide Nanoparticles-Dendrimer Complexes

The ability of Superparamagnetic Iron Oxide (SPIO) nanoparticles and Poly(Propyleneimine) generation 5 dendrimers (PPI G5) to cooperatively provoke siRNA complexation was investigated in order to develop a targeted, multifunctional siRNA delivery system for cancer therapy. Poly(ethylene glycol) (PEG) coating and cancer specific targeting moiety (LHRH peptide) have been incorporated into SPIO-PPI G5-siRNA complexes to enhance serum stability and selective internalization by cancer cells. Such a modification of siRNA nanoparticles enhanced its internalization into cancer cells and increased the efficiency of targeted gene suppression in vitro. Moreover, the developed siRNA delivery system was capable of sufficiently enhancing in vivo antitumor activity of an anticancer drug (Cisplatin). The proposed approach demonstrates potential for the creation of targeted multifunctional nanomedicine platforms with the ability to deliver therapeutic siRNA specifically to cancer cells in order to prevent severe adverse side effects on healthy tissues and in situ monitoring of the therapeutic outcome using clinically relevant imaging techniques.