Cancer-targeted Nanoparticles Research Articles

Folic Acid-Functionalized Nanocrystalline Cellulose as a Renewable and Biocompatible Nanomaterial for Cancer-Targeting Nanoparticles

Folic Acid-Functionalized Nanocrystalline Cellulose as a Renewable and Biocompatible Nanomaterial for Cancer-Targeting Nanoparticles

Preparation, characterization, and in vitro cytotoxicity activity of allyl-isothiocyanate-embedded polymeric nanoparticles for potential breast cancer targeting.

Allyl isothiocyanate (AITC) is an excellent active phytoconstituent recently revealed for cancer treatment. The strategic prominence of this study was to synthesize and characterize AITC-embedded tripolyphosphate-modified chitosan nanoparticles (AITC@CS-TPP-NPs) by ionic gelation. Chitosan is recycled as a polymer to fabricate AITC@CS-TPP-NPs; the fabricated nanoparticles (NPs) are then characterized using FT-IR spectroscopy, DSC, XRD, zeta potential, size analysis, SEM, EDX, entrapment efficiency, in vitro drug release study, and in vitro cytotoxicity activity against MCF-7 to explore the effectiveness and strength. As a result, developed AITC@CS-TPP-NPs demonstrates good stability with a zeta potential of 35.83mV and 90.14% of drug release. The anticancer potential of AITC@CS-TPP-NPs shows the improved cytotoxicityactivity of AITC due to the surface modification of CS using TPP. Hence, the cytotoxicity of AITC@CS-TPP-NPs was tested in vitro against a human breast cancer cell line (MCF-7) and found to be considerable. The AITC@CS-TPP-NPs were effectively synthesized and have significant benefits, including being easy to prepare, stable, and affordable with wide use in human breast cancer against cell line (MCF-7).

Prediction of cancer nanomedicines self-assembled from meta-synergistic drug pairs

Combination therapy is widely used in cancer medicine due to the benefits of drug synergy and the reduction of acquired resistance. To minimize emergent toxicities, nanomedicines containing drug combinations are being developed, and they have shown encouraging results. However, developing multi-drug loaded nanoparticles is highly complex and lacks predictability. Previously, it was shown that single drugs can self-assemble with near-infrared dye, IR783, to form cancer-targeted nanoparticles. A structure-based predictive model showed that only 4% of the drug space self-assembles with IR783. Here, we mapped the self-assembly outcomes of 77 small molecule drugs and drug pairs with IR783. We found that the small molecule drug space can be divided into five types, and type-1 drugs self-assemble with three out of four possible drug types that do not form stable nanoparticles. To predict the self-assembly outcome of any drug pair, we developed a machine learning model based on decision trees, which was trained and tested with F1-scores of 89.3% and 87.2%, respectively. We used literature text mining to capture drug pairs with biological synergy together with synergistic chemical self-assembly and generated a database with 1985 drug pairs for 70 cancers. We developed an online search tool to identify cancer-specific, meta-synergistic drug pairs (both chemical and biological synergism) and validated three different pairs in vitro. Lastly, we discovered a novel meta-synergistic pair, bortezomib-cabozantinib, which formed stable nanoparticles with improved biodistribution, efficacy, and reduced toxicity, even over single drugs, in an in vivo model of head and neck cancer.

Biomimetic Nanoparticles for Cancer Targeting and Drug Delivery

0Cellular membrane engineered nanoparticles (NPs) have shown immense potential for anti-cancer drug delivery applications. In principle, cell membrane of any type of cells can be processed to obtain purified cellular membrane which can self-assemble to form stable and highly robust nanovesicles. These nanovesicles retain lipid-bilayer architecture of host’s cells and much of the surface biomarkers and proteins are conserved during top-down approach. Interestingly, nanovesicles have exhibited long plasma circulation and appreciable tumour specific binding, which is largely suggestive of their biomimetic properties. Many pioneer studies have demonstrated their ability to encapsulate different chemotherapeutic agents and photosensitizers of varied chemical complexities, and releasing them in a triggered fashion. Additionally, the novel NPs system has been developed for cancer immunotherapy. The review discusses some of the important research and applications of cellular membrane derived nanovesicles for different forms of cancer therapy and their potential to be developed as personalized nanomedicine.

Towards epigenetic regulation of triple-negative breast cancer via ligand-mediated nanoparticles.

Aims: Develop and analyze triple-negative breast cancertargeted nanoparticles loaded with the demethylating agent decitabine. Materials & methods: The polymers were synthesized by ring-opening polymerization of D,L-lactide and formulated into nanoparticles via emulsion-evaporation method. The nanoparticles were characterized by physicochemical analysis as well as in vitro using breast cancer cell lineages. Results & conclusion: The targeted nanoparticles exhibited a hydrodynamic diameter of 75±12nm, zetapotential -6.3±0.2mV andspherical morphology, and displayedgreater in vitro accumulation into MDA-MB-231 (triple-negative breast cancer cell-line) compared with MCF7 and HB4A cell lineages as verified by fluorescence confocal microscopy and significant demethylating effects via ADAM33 screening by PCR.

Principles of Nanoparticle Delivery to Solid Tumors.

The effective treatment of patients with cancer hinges on the delivery of therapeutics to a tumor site. Nanoparticles provide an essential transport system. We present 5 principles to consider when designing nanoparticles for cancer targeting: (a) Nanoparticles acquire biological identity in vivo, (b) organs compete for nanoparticles in circulation, (c) nanoparticles must enter solid tumors to target tumor components, (d) nanoparticles must navigate the tumor microenvironment for cellular or organelle targeting, and (e) size, shape, surface chemistry, and other physicochemical properties of nanoparticles influence their transport process to the target. This review article describes these principles and their application for engineering nanoparticle delivery systems to carry therapeutics to tumors or other disease targets.

Induction of ferroptosis using functionalized iron-based nanoparticles for anti-cancer therapy.

Ferroptosis, a cell death pathway that is induced in response to iron, has recently attracted remarkable attention given its emerging therapeutic potential in cancer cells. The need for a promising modality to improve chemotherapy's efficacy through this pathway has been urgent in recent years, and this non-apoptotic cell death pathway accumulates reactive oxygen species (ROS) and is subsequently involved in lipid peroxidation. Here, we report cancer-targeting nanoparticles that possess highly efficient cancer-targeting ability and minimal systemic toxicity, thereby leading to ferroptosis. To overcome the limit of actual clinical application, which is the ultimate goal due to safety issues, we designed safe nanoparticles that can be applied clinically. Nanoparticles containing ferroptosis-dependent iron and FDA-approved hyaluronic acid (FHA NPs) are fabricated by controlling physicochemical properties, and the FHA NPs specifically induce ROS production and lipid peroxidation in cancer cells without affecting normal cells. The excellent in vivo anti-tumor therapeutic effect of FHA NPs was confirmed in the A549 tumor-bearing mice model, indicating that the induction of FHA NP-mediated cell death via the ferroptosis pathway could serve as a powerful platform in anticancer therapy. We believe that this newly proposed FHA NP-induced ferroptosis strategy is a promising system that offers the potential for efficient cancer treatment and provides insight into the safe design of nanomedicines for clinical applications.

Development, evaluation, pharmacokinetic and biodistribution estimation of resveratrol-loaded solid lipid nanoparticles for prostate cancer targeting

Background and aim The study was to extend systemic circulation and biological half-life (t1/2) of trans-resveratrol (RSV) using solid lipid nanoparticles (RSV-SLN) to improve its anti-cancer potential. Methods RSV-SLN was prepared by solvent emulsification evaporation technique and proceeded for evaluation like particle size, PDI, zeta potential, in vitro release, in vitro cytotoxicity, cellular internalisation, haemolysis and erythrocyte membrane integrity, platelet aggregation and pharmacokinetic studies in rats. Moreover, cancer cells accumulation of RSV-SLN also needs to be evaluated for proving their targeting ability. Result Prepared SLN showed 126.85 ± 12.09 nm particle size, −24.23 ± 3.27 mV Zeta potential and 74.67 ± 4.76%. release at 48 h and haemocompatible. The cellular internalisation image showed the SLN reach in a cytoplasm and nucleus of PC3 prostate cells. RSV-SLN exhibited high t1/2 (8.22 ± 1.36 h) and 7.19 ± 0.69 h MRT (Mean residence time) and lower clearance i.e. 286.42 ± 13.64 mL/min/kg. The bio-distribution of RSV-SLN was found to be extremely high in prostate cells and accumulate 7.56 times greater than that of RSV solution. Conclusion The developed RSV-SLN can be applied as potential carrier for delivery of drug of chemotherapeutics at an extend systemic circulation and targeting efficiency at tumour site.

Development and characterization of hyaluronic acid surface scaffolds Encorafenib loaded polymeric nanoparticles for colorectal cancer targeting

For treatment of colorectal cancer and to improve intravascular bioavailability, Encorafenib (ECF) encapsulated Hyaluronic Acid (HA) decorated polycaprolactone (PCL), and polyhydroxybutyrate (PHB) polymeric nanoparticles were prepared. The DLS, SEM, and TEM data show an increase in particle size (<200 nm) after hyaluronic acid conjugation over polymeric nanoparticles. AFM confirms that HA-linked nanoparticles have a rougher surface. FTIR, DSC, XRD, and TGA confirm that HA conjugates form amorphous nanoparticles. The in-vitro drug release study indicated initial burst release of ECF followed by sustain release profile. In vitro cytotoxicity testing revealed that HA-ECF-PHB-NPs significantly inhibited HCT116 cell lines compared to the other three nanoparticles and ECF drug solutions. The genotoxicity of polymeric nanoparticles was assessed by cytokinesis-block micronucleus (CBMN) assay, indicating DNA damage in HCT116 cells and micronuclei and nuclear buds’ formation. The produced nanoparticles can lower ROS, possibly due to their good cellular internalisation and apoptotic arrest. Histopathology of colon tissue following nanoparticle injection showed no injury. Haemolysis, LDH assay showed nanoparticles' biocompatibility. According to fluorescence research, epithelial colon cells accumulate more fluorescent nanoparticles after i.v. administration. The ECF polymeric nanoparticles fabricated with HA can be considered a promising drug delivery system for colorectal cancer therapy.

Hyaluronan self-agglomerating nanoparticles for non-small cell lung cancer targeting

BackgroundOwing to the limited amount of research, there are no nanoparticle-based anticancer agents that use hydrophilic drugs. Therefore, we developed irinotecan-loaded self-agglomerating hyaluronan nanoparticles (ISHNs). While irinotecan has high hydrophilicity, the resulting nanoparticle should possess high anticancer drug-loading capacity and allow selective targeting of the cluster of differentiation 44 (CD44) protein, which is overexpressed on the surface of tumor cells.ResultsThe ISHNs were successfully made with hyaluronan (HA) as a targeting moiety, FeCl3 as a binder, and D-glutamic acid (GA) as a stabilizer. The ISHNs self-agglomerated via chelating bonding and were lyophilized using a freeze dryer. The particle diameter and zeta potential of the ISHNs were 93.8 ± 4.48 nm and − 36.3 ± 0.28 mV, respectively; a relatively narrow size distribution was observed. The drug fixation yield and drug-loading concentration were 58.3% and 1.75 mg/mL, respectively. Affinity studies revealed a tenfold stronger targeting to H23 (CD44+) non-small-cell lung cancer (NSCLC) cells, than of A549 (CD44−) cells.ConclusionWe developed irinotecan-loaded ISHNs, which comprised irinotecan hydrochloride as a water-soluble anticancer agent, HA as a targeting moiety, FeCl3 as a binder for self-agglomeration, and GA as a stabilizer; HA is a binding material for CD44 in NSCLC cells. Owing to their ease of manufacture, excellent stability, non-cell toxicity and CD44-targeting ability, ISHNs are potential nanocarriers for passive and active tumor targeting.

Structural and Functional Characterizations of Cancer Targeting Nanoparticles Based on Hepatitis B Virus Capsid.

Cancer targeting nanoparticles have been extensively studied, but stable and applicable agents have yet to be developed. Here, we report stable nanoparticles based on hepatitis B core antigen (HBcAg) for cancer therapy. HBcAg monomers assemble into spherical capsids of 180 or 240 subunits. HBcAg was engineered to present an affibody for binding to human epidermal growth factor receptor 1 (EGFR) and to present histidine and tyrosine tags for binding to gold ions. The HBcAg engineered to present affibody and tags (HAF) bound specifically to EGFR and exterminated the EGFR-overexpressing adenocarcinomas under alternating magnetic field (AMF) after binding with gold ions. Using cryogenic electron microscopy (cryo-EM), we obtained the molecular structures of recombinant HAF and found that the overall structure of HAF was the same as that of HBcAg, except with the affibody on the spike. Therefore, HAF is viable for cancer therapy with the advantage of maintaining a stable capsid form. If the affibody in HAF is replaced with a specific sequence to bind to another targetable disease protein, the nanoparticles can be used for drug development over a wide spectrum.

Salicylic acid-loaded chitosan nanoparticles (SA/CTS NPs) for breast cancer targeting: Synthesis, characterization and controlled release kinetics

The present study aimed to develop an easy controlled release system for salicylic acid (SA) through ionotropic gelation of chitosan (CTS) using tripolyphosphate (TPP) as cross-linker. The synthesized nanoparticles (SA/CTS NPs) were characterized for their physicochemical properties by various techniques including Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), scanning electron microscopy (SEM) with an energy-dispersive X-ray (EDX) spectroscopy, X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). A maximum encapsulation efficiency (EE) of 84% was obtained. The obtained material not only was tested as drug delivery system in neutral (pH 7.4) and acidic medium (pH 5.5) but also the kinetic release behavior of SA from the CTS NPs was investigated based on two models namely Korsmeyer-Peppas and Higuchi. These data demonstrated that the drug release mechanism governed by Korsmeyer-Peppas model. Finally, the cytotoxic effects of free SA and SA/CTS NPs were evaluated in-vitro against breast cancer (MDA-MB-231) cell lines by MTT assay. Results showed that SA/CTS NPs were more cytotoxic than free SA. This work suggested the potential of SA/CTS NPs system as an effective anticancer system.

Cell membrane biomimetic nanoparticles for inflammation and cancer targeting in drug delivery.

Nanoparticle capture and elimination by the immune system are great obstacles for drug delivery. Camouflaging nanoparticles with cell membrane represents a promising strategy to communicate and negotiate with the immune system. As a novel class of nanotherapeutics, such biomimetic nanoparticles inherit specific biological functionalities of the source cells (e.g., erythrocytes, immune cells, cancer cells and platelets) in order to evade immune elimination, prolong circulation time, and even target a disease region by virtue of the homing tendency of the cell membrane protein. In this review, we begin with an overview of different cell membranes that can be utilized to create a biointerface on nanoparticles. Subsequently, we elaborate on the state-of-the-art of cell membrane biomimetic nanoparticles for drug delivery. In particular, a summary of data on circulation capacity and targeting efficiency by camouflaged nanoparticles is presented. In addition to cancer therapy, inflammation treatment, as an emerging application of biomimetic nanoparticles, is specifically included. The challenges and outlook of this technology are discussed.

Tuning the size, shape and structure of RNA nanoparticles for favorable cancer targeting and immunostimulation.

The past decade has shown exponential growth in the field of RNA nanotechnology. The rapid advances of using RNA nanoparticles for biomedical applications, especially targeted cancer therapy, suggest its potential as a new generation of drug. After the first milestone of small molecule drugs and the second milestone of antibody drugs, it was predicted that RNA drugs, either RNA itself or chemicals/ligands that target RNA, will be the third milestone in drug development. Thus, a comprehensive assessment of the current therapeutic RNA nanoparticles is urgently needed to meet the drug evaluation criteria. Specifically, the pharmacological and immunological profiles of RNA nanoparticles need to be systematically studied to provide insights in rational design of RNA-based therapeutics. By virtue of its programmability and biocompatibility, RNA molecules can be designed to construct sophisticated nanoparticles with versatile functions/applications and highly tunable physicochemical properties. This intrinsic characteristic allows the systemic study of the effects of various properties of RNA nanoparticles on their in vivo behaviors such as cancer targeting and immune responses. This review will focus on the recent progress of RNA nanoparticles in cancer targeting, and summarize the effects of common physicochemical properties such as size and shape on the RNA nanoparticles' biodistribution and immunostimulation profiles. This article is categorized under: Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures Diagnostic Tools > in vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Cancer-Targeting Nanoparticles for Combinatorial Nucleic Acid Delivery.

Nucleic acids are a promising type of therapeutic for the treatment of a wide range of conditions, including cancer, but they also pose many delivery challenges. For efficient and safe delivery to cancer cells, nucleic acids must generally be packaged into a vehicle, such as a nanoparticle, that will allow them to be taken up by the target cells and then released in the appropriate cellular compartment to function. As with other types of therapeutics, delivery vehicles for nucleic acids must also be designed to avoid unwanted side effects; thus, the ability of such carriers to target their cargo to cancer cells is crucial. Classes of nucleic acids, hurdles that must be overcome for effective intracellular delivery, types of nonviral nanomaterials used as delivery vehicles, and the different strategies that can be employed to target nucleic acid delivery specifically to tumor cells are discussed. Additonally, nanoparticle designs that facilitate multiplexed delivery of combinations of nucleic acids are reviewed.

High Affinity to Skeleton Rare Earth Doped Nanoparticles for Near-Infrared II Imaging.

As a newly noninvasive emerging modality, NIR-II fluorescence imaging (1000-1700 nm) has many advantages over conventional visible and NIR-I imaging (700-900 nm). Unfortunately, only a few NIR-II fluorophores are suitable for bone imaging. Here, we report an NIR-II fluorophore based on DSPE-mPEG encapsulated rare earth doped nanoparticles (RENPs@DSPE-mPEG), which shows inherent affinity to bone without linking any targeting ligands, and thus, it provides an alternative noninvasive and nonradiation strategy for skeletal system mapping and bone disease diagnoses. Interestingly, within the NIR-II window, imaging at a longer wavelength (1345 nm) provides a higher resolution and signal-to-noise ratio than imaging at 1064 nm, even though the quantum yield at 1064 nm is 2-fold higher than that at 1345 nm. Besides bone imaging, RENPs@DSPE-mPEG show an imaging application in blood vessels and lymph nodes. Importantly, RENPs@DSPE-mPEG can be internalized by circulating white blood cells. This finding may open a window to increase efficient nanoparticle delivery in the fields such as immunotherapy and improve the diagnostic and therapeutic efficacy of cancer-targeted nanoparticles in clinical applications.

Dimeric Prodrug Self-Delivery Nanoparticles with Enhanced Drug Loading and Bioreduction Responsiveness for Targeted Cancer Therapy.

Efficient drug accumulation in tumor cells is essential for cancer therapy. Herein, we developed dimeric prodrug self-delivery nanoparticles (NPs) with enhanced drug loading and bioreduction responsiveness for triple negative breast cancer (TNBC) therapy. Specially designed camptothecin dimeric prodrug (CPTD) containing a disulfide bond was constructed to realize intracellular redox potential controlled drug release. Direct conjugation of hydrophobic CPTD to poly(ethylene glycol) PEG5000, a prodrug-based amphiphilic CPTD-PEG5000 co-polymer was synthesized, which could encapsulate parental CPTD prodrug spontaneously and form ultrastable NPs due to the highly analogous structure. Such dimeric prodrug self-delivery nanoparticles showed ultrahigh stability with critical micelle concentration as low as 0.75 μg/mL and remained intact during endocytosis. In addition, neurotensin (NT), a 13 amino acid ligand, was further modified on the nanoparticles for triple negative breast cancer (TNBC) targeting. Optimized NT-CPTD NPs showed improved pharmacokinetics profile and increased drug accumulation in TNBC lesions than free CPT, which largely reduced the systemic toxicity and presented an improved anticancer efficacy in vivo. In summary, with advantages of extremely high drug loading capacity, tumor microenvironmental redox responsiveness, and targeted TNBC accumulation, NT-CPTD NPs showed their potential for effective triple negative breast cancer therapy.

Genetic Assembly of Double-Layered Fluorescent Protein Nanoparticles for Cancer Targeting and Imaging.

Hepatitis B virus capsid (HBVC), a self‐assembled protein nanoparticle comprised of 180 or 240 subunit proteins, is used as a cage for genetic encapsulation of fluorescent proteins (FPs). The self‐quenching of FPs is controlled by varying the spacing between FPs within the capsid structure. Double‐layered FP nanoparticle possessing cancer cell‐targeting capabilities is also produced by additionally attaching FPs and cancer cell receptor‐binding peptides (affibodies) to the outer surface of the capsid. The generically modified HBVC with double layers of mCardinal FPs and affibodies (mC‐DL‐HBVC) exhibit a high fluorescence intensity and a strong photostability, and is efficiently internalized by cancer cells and significantly stable against intracellular degradation. The mC‐DL‐HBVC effectively detects tumor in live mice with enhanced tumor targeting and imaging efficiency with far less accumulation in the liver, compared to a conventional fluorescent dye, Cy5.5. This suggests the great potential of mC‐DL‐HBVC as a promising contrast agent for in vivo tumor fluorescence imaging.

Epidermal growth factor (EGF) fragment-guided anticancer theranostic particles for pH-responsive release of doxorubicin

EGF fragment (EGFfr) and doxorubicin were chemically co-decorated on single magnetic nanoparticles (MNPs) for concomitant cancer targeting and treatment. Magnetic nanoparticles were prepared by the precipitation of ferric chloride hydrates in an ammonia solution and subsequent surface-functionalization with amines. The terminal thiol group of the EGF fragment was first conjugated to surface amines of the MNPs using a heterofunctional crosslinker, and doxorubicin was sequentially conjugated to the MNPs via a hydrazone linker, where the degree of subsitution of the surface amines to EGFfr was varied from 1% to 40%. The decorated doxorubicin showed clear pH-dependency in the release profile, and doxorubicin showed fast release at pH 5.0 in comparison to pH 7.4. The EGF-decorated MNPs were tested for differential cellular uptakes against EGF overexpressing cells (A549), and the uptake levels gradually increased to 10% and saturated, which was quantified by ICP-OES. Internalized doxorubicin was also visualized by confocal microscopy, and A549 cells with EGF-decorated MNPs with EGF decoration showed higher fluorescence intensity of doxorubicin than those with non-decorated MNPs. Anti-cancer activity of the MNPs was compared at various concentrations of doxorubicin and EGFfr. Decoration of EGFfr significantly increased the anti-cancer activity of doxorubicin-incorporated MNPs in A549 cells; however, EGFfr alone did not affect the viability of the cells. Thus, we concluded that MNPs with optimized EGFfr and doxorubicin ratios showed higher targeting and drug payload against EGF receptor overexpressing cancer cells.

Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles

Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles