Nanomedicine For Drug Delivery Research Articles

(Invited) Designing Quantum Dots for Multiplexed Deep-Tissue Imaging in the NIR-II

The combination of bright, tunable semiconductor quantum dots (QDs) emitting in the shortwave infrared or second near infrared window (SWIR/NIR-II, 1000 – 1600 nm) and InGaAs camera-equipped preclinical imagers opens the door to non-invasive, multiplexed, deep tissue imaging in live mice. While imaging in the NIR-I is like imaging through fog due to highly scattering tissue, imaging in the SWIR/NIR-II is more like imaging through pond water, enabling deeper imaging with much improved resolution. We synthesized multiple PbS/CdS core/shell QDs with emission wavelengths spanning 1000-1600 nm. These particles have been encapsulated in lipid-PEG micelles and up to three colors (so far) dosed into nude mice for imaging on a Photon Etc IR VIVO imager equipped with a hyperspectral Bragg grating and 6 bandpass filters, enabling demixing of the discrete colors. We have obtained exceptionally clear images of lymphatic drainage and the vasculature system, including visualization of lymphatic valve opening in videos. Interestingly, following intravascular injection, the liver and spleen are very visible and distinct, enabling the non-invasive visualization of a key nanomedicine drug delivery parameter (i.e., are the nanoparticles accumulating in the liver or the spleen?). Image processing investigations are expanding our ability to demix colors as well as to determine the average depth of the contrast agent, based on the wavelength-dependent attenuation of the photoluminescence based on water absorption. In addition to the photophysical advantages of using QDs for NIR-II, elemental analysis of blood and tissue samples enables quantitative biodistribution and pharmacokinetic studies. Ongoing work involves the application of this imaging approach to assess the impact nanomaterial surface properties and route of delivery on their pharmacokinetics and the use of deep tissue paired agent imaging for non-invasive “optical biopsy” of orthotopic tumors. Current data are already visually stunning, and ongoing imaging highlights new opportunities for research with every experiment! Figure 1

Microneedle-mediated nanomedicine to enhance therapeutic and diagnostic efficacy.

Nanomedicine has been extensively explored for therapeutic and diagnostic applications in recent years, owing to its numerous advantages such as controlled release, targeted delivery, and efficient protection of encapsulated agents. Integration of microneedle technologies with nanomedicine has the potential to address current limitations in nanomedicine for drug delivery including relatively low therapeutic efficacy and poor patient compliance and enable theragnostic uses. In this Review, we first summarize representative types of nanomedicine and describe their broad applications. We then outline the current challenges faced by nanomedicine, with a focus on issues related to physical barriers, biological barriers, and patient compliance. Next, we provide an overview of microneedle systems, including their definition, manufacturing strategies, drug release mechanisms, and current advantages and challenges. We also discuss the use of microneedle-mediated nanomedicine systems for therapeutic and diagnostic applications. Finally, we provide a perspective on the current status and future prospects for microneedle-mediated nanomedicine for biomedical applications.

Applications of graphene-based nanomaterials in drug design: The good, the bad and the ugly

ABSTRACT Introduction Graphene-based materials (GBMs) have unique physicochemical properties that make them extremely attractive as platforms for the design of new drugs. Indeed, their bidimensional (2D) morphology, high surface area, mechanical and optical properties, associated to different possibilities for functionalization of their surface, provides opportunities for their use as nanomedicines for drug delivery and/or phototherapies. Areas covered This opinion paper provides an overview of the current status of GBMs in drug design, with a focus on their therapeutic applications, potential environmental and health risks, and some controversial results. The authors discuss the chemical modifications of GBMs for the treatment of various diseases. The potential toxicity associated with some GBMs is also presented, along with a safe-by-design approach to minimize the risks. Finally, the authors address some issues associated to the use of GBMs in the biomedical field, such as contradictory antibacterial effects, fluorescence quenching and imprecise chemical functionalization. Expert opinion GBMs are a promising and exciting area of research in drug delivery. It is however important that responsible and safe use of these materials is ensured to fully exploit their advantages and overcome their drawbacks.

Lipid nanoparticles as theranostic vesicle

Lipid nanoparticles (LNP) are the most well-studied first approved nanomedicine for drug delivery of therapeutic and vaccine formulation products. However, their nature is under constant investigation especially their liquid crystal state which leads to their complex biological behavior. LNPs are generally regarded as safe (GRAS) and suitable for ameliorating the toxicity and/or improving the pharmacokinetics of newly approved biomaterials with promising functionality and effects. During the past decade, many promising theranostic applications for LNPs have emerged resulting in huge potential for them in this field. Although there is progress in theranostic application, the gap between the bench and clinical application is undeniable, and that must be addressed to exploit the benefits of these nanomedicines for society.

Diffusiophoresis of a Weakly Charged Liquid Metal Droplet.

Diffusiophoresis of a weakly charged liquid metal droplet (LMD) is investigated theoretically, motivated by its potential application in drug delivery. A general analytical formula valid for weakly charged condition is adopted to explore the droplet phoretic behavior. We determined that a liquid metal droplet, which is a special category of the conducting droplet in general, always moves up along the chemical gradient in sole chemiphoresis, contrary to a dielectric droplet where the droplet tends to move down the chemical gradient most of the time. This suggests a therapeutic nanomedicine such as a gallium LMD is inherently superior to a corresponding dielectric liposome droplet in drug delivery in terms of self-guiding to its desired destination. The droplet moving direction can still be manipulated via the polarity dependence; however, there should be an induced diffusion potential present in the electrolyte solution under consideration, which spontaneously generates an extra electrophoresis component. Moreover, the smaller the conducting liquid metal droplet is, the faster it moves in general, which means a smaller LMD nanomedicine is preferred. These findings demonstrate the superior features of an LMD nanomedicine in drug delivery.

Rücktitelbild: Novel Strategy to Drive the Intracellular Uptake of Lipid Nanoparticles for Photodynamic Therapy (Angew. Chem. 16/2023)

The superior efficacy of aminopolycarboxylic acid conjugated lipid nanoparticles over standard liposomal nanoparticles is described by Juan Chen, Gang Zheng et al. in their Research Article (e202218218). EDTA–lipid based nanoparticles fluidize the cell membrane in a detergent-like manner and improve delivery to the cell by 25-fold. This novel nanoparticle design feature can be deployed across lipid nanoparticles to accelerate cancer nanomedicine drug delivery.

Back Cover: Novel Strategy to Drive the Intracellular Uptake of Lipid Nanoparticles for Photodynamic Therapy (Angew. Chem. Int. Ed. 16/2023)

The superior efficacy of aminopolycarboxylic acid conjugated lipid nanoparticles in comparison to standard liposomal nanoparticles is described by Juan Chen, Gang Zheng et al. in their Research Article (DOI: 10.1002/anie.20218218). EDTA–lipid incorporated nanoparticles fluidize the cell membrane in a detergent-like manner and improve delivery to the cell by 25-fold. This novel nanoparticle design feature can be deployed across lipid nanoparticles to accelerate cancer nanomedicine drug delivery.

Engineering near-infrared laser-activated gold nanorod vesicles with upper critical solution temperature for photothermal therapy and chemotherapy

Multimodal synergistic therapy based on nanomedicine drug delivery systems can achieve accurate cancer treatment. The anisotropy of gold nanorods (AuNRs) allows the adjustment of the longitudinal localized surface plasmon resonance absorption to the near-infrared band, which shows potential application in the field of photothermal therapy of cancer. Here, we report a new type of thermal-sensitive gold nanorod drug-loaded vesicles (UGRV-DOX) via the self-assembly of AuNRs modified with the amphiphilic polymer (PEG45-b-PS150) and upper critical solution temperature (UCST) polymer (P(AAm-co-AN)). The hollow structure of the vesicle can increase the drug loading capacity, and the polymers on its surface are intertwined to reduce drug leakage. As-prepared UGRV-DOX vesicles exhibits excellent photothermal conversion efficiency and can achieve light-controlled drug release. In vivo anti-tumor experiments showed that UGRV-DOX could ablate HepG2 transplanted tumors significantly under 808 nm laser irradiation, and the inhibition rate was as high as 99.3 %. These tumor-specific nanovesicles prefigure great potentials for high-precision cancer treatment.

Drug Delivery of Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) to Target Brain Tumors.

Brain, predisposed to local and metastasized tumors, has always been the focus of oncological studies. Glioblastoma multiforme (GBM), the most common invasive primary tumor of the brain, is responsible for 4% of all cancer-related deaths worldwide. Despite novel technologies, the average survival rate is 2 years. Physiological barriers such as blood-brain barrier (BBB) prevent drug molecules penetration into brain. Most of the pharmaceuticals present in the market cannot infiltrate BBB to have their maximum efficacy and this in turn imposes a major challenge. This mini review discusses GBM and physiological and biological barriers for anticancer drug delivery, challenges for drug delivery across BBB, drug delivery strategies focusing on SLNs and NLCs and their medical applications in on-going clinical trials. Numerous nanomedicines with various characteristics have been introduced in the last decades to overcome the delivery challenge. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were introduced as oral drug delivery nanomedicines which can be encapsulated by both hydrophilic and lipophilic pharmaceutical compounds. Their biocompatibility, biodegradability, lower toxicity and side effects, enhanced bioavailability, solubility and permeability, prolonged half-life and stability and finally tissue-targeted drug delivery makes them unique among all.

Covalent organic framework nanomedicines: Biocompatibility for advanced nanocarriers and cancer theranostics applications.

Nanomedicines for drug delivery and imaging-guided cancer therapy is a rapidly growing research area. The unique properties of nanomedicines have a massive potential in solving longstanding challenges of existing cancer drugs, such as poor localization at the tumor site, high drug doses and toxicity, recurrence, and poor immune response. However, inadequate biocompatibility restricts their potential in clinical translation. Therefore, advanced nanomaterials with high biocompatibility and enhanced therapeutic efficiency are highly desired to fast-track the clinical translation of nanomedicines. Intrinsic properties of nanoscale covalent organic frameworks (nCOFs), such as suitable size, modular pore geometry and porosity, and straightforward post-synthetic modification via simple organic transformations, make them incredibly attractive for future nanomedicines. The ability of COFs to disintegrate in a slightly acidic tumor microenvironment also gives them a competitive advantage in targeted delivery. This review summarizes recently published applications of COFs in drug delivery, photo-immuno therapy, sonodynamic therapy, photothermal therapy, chemotherapy, pyroptosis, and combination therapy. Herein we mainly focused on modifications of COFs to enhance their biocompatibility, efficacy and potential clinical translation. This review will provide the fundamental knowledge in designing biocompatible nCOFs-based nanomedicines and will help in the rapid development of cancer drug carriers and theranostics.

SYNTHETIC AND APPLICATION OF NANOPARTICLES DRUG DELIVERY SYSTEMS PRESENT AND FUTURE PROSPECTIVE

Materials in the nanoscale range are used as diagnostic tools or to deliver therapeutic medicines to precisely targeted locations using nano delivery systems, a relatively new but fast emerging field of medicine. By delivering precise medicines to specified sites and targets, nanotechnology has the potential to significantly improve the treatment of chronic human diseases. Recently, there have been a number of remarkable uses of nanomedicine (chemotherapeutic agents, biological agents, immunotherapeutic agents, etc.) in the treatment of various disorders. Clinical uses of nanomedicines, both current and potential, are reviewed, as are the advantages and disadvantages of nanomedicines for drug delivery from synthetic/natural sources. We have also included data on future predictions and developments in the field of nanomedicine.

Advanced in Nanomedicine Drug Delivery Application for HIV Therapy

HIV is the chronic disease and patient adherence to treatment is critical over a lifetime Nanomedicine Application can improve a variety of pharmacological problem from Increasing bioavailability to specific targeting to the site of action.The application of Nanomedicine to present and future HIV treatment may offer bespoke solution to the problem faced by established formulated drug. In this review We are discuss about the advance in Nanomedicine drug delivery application for HIV therapy. poor aqueous drug solubility is the major limitation negativity impating oral bioavailability for many antiretraviral drug.HIV is a long term disease patient adherence therapy is critical over a lifetime.

Nano-molecularly imprinted polymers (nanoMIPs) as a novel approach to targeted drug delivery in nanomedicine.

Molecularly imprinted polymers – MIPs – denote synthetic polymeric structures that selectively recognize the molecule of interest against which MIPs are templated. A number of works have demonstrated that MIPs can exceed the affinity and selectivity of natural antibodies, yet operating by the same principle of “lock and key”. In contrast to antibodies, which have certain limitations related to the minimal size of the antigen, nanoMIPs can be fabricated against almost any target molecule irrespective of its size and low immunogenicity. Furthermore, the cost of MIP production is much lower compared to the cost of antibody production. Excitingly, MIPs can be used as nanocontainers for specific delivery of therapeutics both in vitro and in vivo. The adoption of the solid phase synthesis rendered MIPs precise reproducible characteristics and, as a consequence, improved the controlled release of therapeutic payloads. These major breakthroughs paved the way for applicability of MIPs in medicine as a novel class of therapeutics. In this review, we highlight recent advances in the fabrication of MIPs, mechanisms of controlled release from the MIPs, and their applicability in biomedical research.

Collective guiding of acoustically propelled nano- and microparticles.

One of the most important potential applications of motile nano- and microdevices is targeted drug delivery. To realize this, biocompatible particles that can be guided collectively towards a target inside a patient's body are required. Acoustically propelled nano- and microparticles constitute a promising candidate for such biocompatible, artificial motile particles. The main remaining obstacle to targeted drug delivery by motile nano- and microdevices is to also achieve a reliable and biocompatible method for guiding them collectively to their target. Here, we propose such a method. As we confirm by computer simulations, it allows for the remote guiding of large numbers of acoustically propelled particles to a prescribed target by combining a space- and time-dependent acoustic field and a time-dependent magnetic field. The method works without detailed knowledge about the particle positions and for arbitrary initial particle distributions. With these features, it paves the way for the future application of motile particles as vehicles for targeted drug delivery in nanomedicine.

Multifunctional Magnetic Nanomedicine Drug Delivery and Imaging‐Based Diagnostic Systems

AbstractMagnetically guided drug transportation is a technique in which magnetic pharmaceutical transporters in organisms are controlled by applied magnetic forces to deliver drugs to the desired location. Different magnetic drug delivery systems (MDDSs) are developed to treat a variety of illnesses, particularly cancer and neurological disorders. However, a unique magnetic setup is required in each application for an effective magnetically guided drug aiming to direct the drug‐carrying nanocarriers to the intended area. The current and future perspectives of MDDS are investigated in this study by considering their biological functions, deliverable efficiency, complexity, and the nature of the externally applied magnetic field. Despite the fact that MDDSs have low cytotoxicity, regulated magneto reactivity, extended circulation lifespan, and high surface stability, very few clinical studies have been conducted to date in order to achieve optimized therapeutic efficacy before entering the market. In recent studies, the development of novel magnetic medication transporting carriers is preferred over direct magnetic medication administration. Better functional magnetic targeting technologies are required for such breakthroughs to enter clinical trials. Because MDDSs are unlikely to work in all clinical situations, more focused research is needed to replace or improve the strategy for treating multiple illnesses.

Recent Advances of Microfluidic Platforms for Controlled Drug Delivery in Nanomedicine.

Nanomedicine drug delivery systems hold great potential for the therapy of many diseases, especially cancer. However, the controlled drug delivery systems of nanomedicine bring many challenges to clinical practice. These difficulties can be attributed to the high batch-to-batch variations and insufficient production rate of traditional preparation methods, as well as a lack of technology for fast screening of nanoparticulate drug delivery structures with high correlation to in vivo tests. These problems may be addressed through microfluidic technology. Microfluidics, for example, can not only produce nanoparticles in a well-controlled, reproducible, and high-throughput manner, but it can also continuously create three-dimensional environments to mimic physiological and/or pathological processes. This overview gives a top-level view of the microfluidic devices advanced to put together nanoparticulate drug delivery systems, including drug nanosuspensions, polymer nanoparticles, polyplexes, structured nanoparticles and therapeutic nanoparticles. Additionally, highlighting the current advances of microfluidic systems in fabricating the more and more practical fashions of the in vitro milieus for fast screening of nanoparticles was reviewed. Overall, microfluidic technology provides a promising technique to boost the scientific delivery of nanomedicine and nanoparticulate drug delivery systems. Nonetheless, digital microfluidics with droplets and liquid marbles is the answer to the problems of cumbersome external structures, in addition to the rather big pattern volume. As the latest work is best at the proof-of-idea of liquid-marble-primarily based on totally virtual microfluidics, computerized structures for developing liquid marble, and the controlled manipulation of liquid marble, including coalescence and splitting, are areas of interest for bringing this platform toward realistic use.

Nanoemulsions for drug delivery

Emulsions are liquid–liquid dispersions with one liquid phase dispersed in the other liquid phase as small droplets. Nanoemulsions are nano-sized emulsions with sizes ranging from tens to hundreds of nanometers, and have great potential applications in pharmaceutics, foods and cosmetics due to their attractive properties, such as small sizes, high surface area per unit volume, improved dispersion of active hydrophobic components and enhanced absorption. The article provides an overview of nanoemulsions for drug delivery, starting with an introduction of emulsion types, nanoemulsion preparation and nanoemulsion stability. Surfactants play critical roles in producing and stabilizing nanoemulsions. Different types of surfactants are summarized including small molecule surfactants, particle surfactants, phospholipids, peptide and protein surfactants. Then the applications of nanoemulsions as nanomedicine in drug delivery are presented. Finally, clinical applications of nanoemulsions are discussed.

Biodegradable Dendritic Polyglycerol Sulfate for the Delivery and Tumor Accumulation of Cytostatic Anticancer Drugs.

Targeted delivery and extended blood circulation of anticancer drugs have been the challenges for decreasing the adverse side effects and improving the therapeutic efficiency in cancer chemotherapy. Herein, we present a drug delivery system (DDS) based on biodegradable dendritic polyglycerol sulfate-bearing poly(caprolactone) (dPGS-PCL) chains, which has been synthesized on 20 g scale using a straightforward two-step protocol. In vivo fluorescence imaging demonstrated a significant accumulation of the DDS in the tumor environment. Sunitinib, an anticancer drug, was loaded into the DDS and the drug-induced toxicity was investigated in vitro and in vivo. The drug encapsulated in dPGS-PCL and the free drug showed similar toxicities in A431 and HT-29 cells, and the cellular uptake was comparable. The straightforward and large-scale synthesis, the organic solvent-free drug-loading approach, together with the tumor targetability of the biodegradable dendritic polyglycerols, render this copolymer a promising candidate for targeted cancer nanomedicine drug delivery systems.

CD147 Monoclonal Antibody Targeted Reduction-Responsive Camptothecin Polyphosphoester Nanomedicine for Drug Delivery in Hepatocellular Carcinoma Cells.

In the treatment of tumor-targeted small-molecule anti-cancer drugs, antibody-mediated therapies, especially for antibody-drug conjugates (ADCs), have revealed great latent force. However, the therapeutic drugs provided by ADCs possess limitation. Considering that the combination of antibodies and nano-drugs can broaden their applicability in the field of tumor treatment, herein, we developed an antibody conjugated polymeric prodrug nanoparticles SAE-PEG-b-PBYP-ss-CPT for targeted camptothecin (CPT) delivery to liver tumor cells. The diblock copolymer was composed of PEG and biodegradable polyphosphoester (PBYP) containing alkynyl groups in the side chain. A derivative of CPT (CPT-ss-N3) was bonded to the PBYP via "click" reaction. The diethyl squarate (SAE) in the terminal of PEG chain was used as a functional group to bond with CD147 monoclonal antibody (CD147 mAb). The particle size and size distribution of the both nanoparticles, with antibody binding (namely CD147-CPT NPs) and without antibody (abbreviated as CPT-loaded NPs), were measured by dynamic light scattering (DLS). The morphologies of both two kinds of nanoparticles were observed by transmission electron microscope (TEM). The results of X-ray photoelectron spectroscopy (XPS) showed that CD147 mAb had been coupled to the surface of CPT-loaded NPs. Endocytosis test indicated that CD147-CPT NPs had higher uptake rate and accumulation in HepG2 cells than those of CPT-loaded NPs without antibodies, due to CD147 mAb can specifically bind to CD147 protein overexpressed in HepG2 cells. We establish a method to bond monoclonal antibodies to anti-cancer polymeric prodrugs, and endow biodegradable polymeric prodrugs with precise targeting functions to liver cancer cells.

Tailoring Antifouling Properties of Nanocarriers via Entropic Collision of Polymer Grafting.

Polymer graftings (PGs) are widely employed in antifouling surfaces and drug delivery systems to regulate the interaction with a foreign environment. Through molecular dynamics simulations and scaling theory analysis, we investigate the physical antifouling properties of PGs via their collision behaviors. Compared with mushroom-like PGs with low grafting density, we find brush-like PGs with high grafting density could generate large deformation-induced entropic repulsive force during a collision, revealing a microscopic mechanism for the hop motions of polymer-grafted nanoparticles for drug delivery observed in experiment. In addition, the collision elasticity of PGs is found to decay with the collision velocity by a power law, i.e., a concise dynamic scaling despite the complex process involved, which is beyond expectation. These results elucidate the dynamic interacting mechanism of PGs, which are of immediate interest for a fundamental understanding of the antifouling performance of PGs and the rational design of PG-coated nanoparticles in nanomedicine for drug delivery.