Delivery System For Cancer Therapy Research Articles

Limited Impact of the Protein Corona on the Cellular Uptake of PEGylated Zein Micelles by Melanoma Cancer Cells.

The formation of a protein layer “corona” on the nanoparticle surface upon entry into a biological environment was shown to strongly influence the interactions with cells, especially affecting the uptake of nanomedicines. In this work, we present the impact of the protein corona on the uptake of PEGylated zein micelles by cancer cells, macrophages, and dendritic cells. Zein was successfully conjugated with poly(ethylene glycol) (PEG) of varying chain lengths (5K and 10K) and assembled into micelles. Our results demonstrate that PEGylation conferred stealth effects to the zein micelles. The presence of human plasma did not impact the uptake levels of the micelles by melanoma cancer cells, regardless of the PEG chain length used. In contrast, it decreased the uptake by macrophages and dendritic cells. These results therefore make PEGylated zein micelles promising as potential drug delivery systems for cancer therapy.

Magnetic ZnO/CdO Nanocomposite for Effective Drug Delivery System for Cancer Therapy

ZnO, ZnO/CdO, and Magnetic Ni-ZnO/CdO nanocomposite have been eco-friendly synthesized using Black Rice Husk Extract (BRHE) and water instead of hazardous chemicals and solvents. The anticancer drug Doxorubicin (Dox) was loaded on the PVA-coated biomimetic nanomaterials. The successful synthesis of the pure nanomaterials and the Dox-nanomaterial systems has been confirmed by evaluating their structural, crystalline, textural, surface, and optical properties using various characterization techniques. The Dox-nanomaterials systems were used as anticancer drugs against HEPG2 cells as a model of human cancerous cells. The in vitro Dox release was slower and more sustained from Ni-ZnO/CdO composite compared to the other individual nanomaterials, suggesting that a hydrogen bond strongly attached more Dox molecules to the surface Ni-ZnO/CdO. Moreover, the cytotoxicity investigations on the HEPG2 cell line showed that higher toxicity was obtained by Ni-doped nanocomposite, consistent with the results of in vitro release. This study provides novel magnetic Nanocarriers that can be used as anticancer drug delivery systems after more in vivo investigations on animals or clinical investigations.

Design of Turmeric Rhizome Extract Nano-Formula for Delivery to Cancer Cells.

Novel turmeric rhizome extract nanoparticles (TE-NPs) were developed from fractions of dried turmeric (Curcuma longa Linn.) rhizome. Phytochemical studies, by using HPLC and TLC, of the fractions obtained from ethanol extraction and solvent–solvent extraction showed that turmeric rhizome ethanol extract (EV) and chloroform fraction (CF) were composed mainly of three curcuminoids and turmeric oil. Hexane fraction (HE) was composed mainly of turmeric oil while ethyl acetate fraction (EA) was composed mainly of three curcuminoids. The optimal TE-NPs formulation with particle size of 159.6 ± 1.7 nm and curcumin content of 357.48 ± 8.39 µM was successfully developed from 47-run D-optimal mixture–process variables experimental design. Three regression models of z-average, d50, and d90 could be developed with a reasonable accuracy of prediction (predicted r2 values were in the range of 0.9120–0.9992). An in vitro cytotoxicity study using MTT assay demonstrated that the optimal TE-NPs remarkably exhibited the higher cytotoxic effect on human hepatoma cells, HepG2, when compared with free curcumin. This study is the first to report nanoparticles prepared from turmeric rhizome extract and their cytotoxic activity to hepatic cancer cells compared with pure curcumin. These nanoparticles might serve as a potential delivery system for cancer therapy.

Exosomes as Drug Carriers in Anti-Cancer Therapy.

Over the years, there has been a high demand for developing new safe and effective drug carriers for cancer therapy. Emerging studies have indicated that exosomes can serve as potent therapeutic carriers since they offer low immunogenicity, high stability, innate and acquired targetability, and the stimulation of anti-cancer immune responses. Yet, the development of exosome-based drug delivery systems remains challenging due to their heterogeneity, low yield, and limited drug loading efficiency. Herein, we summarized the current application of exosomes derived from different cells as drug carriers in anti-cancer therapy in vitro and in vivo. We also discussed the challenges and prospects of exosome-based drug delivery systems in cancer therapy.

Stability-tunable core-crosslinked polymeric micelles based on an imidazole-bearing block polymer for pH-responsive drug delivery

Polymeric micelles from block copolymers have gained increasing attention in cancer drug delivery. However, the fabrication of polymeric micelles that are stable in biological fluids and unstable at tumor sites remains a principal challenge. To achieve the tunable stability for the polymeric micelles, Zn coordination-induced core-crosslinked polymeric micelles have been proposed and confirmed. Herein, a block copolymer bearing imidazole pendants is synthesized which is capable of self-assembling into polymeric micelles in water. After core-crosslinking, it can be found that the critical micelle concentration (CMC) of the core-crosslinked polymeric micelles is significantly lower than that of non-crosslinked polymeric micelles. Particularly, the drug-loaded core-crosslinked polymeric micelles are fragile and easily affected by the slightly acidic environments, which makes it possible to turn the polymeric micelles back to hydrophilic polymers and therefore disassemble micelles to unload cargoes. The drug-loaded core-crosslinked polymeric micelles display adequate toxicity as a result of their low IC50 value of 3.713 ± 0.166 μg/mL. Collectively, Zn coordination-induced core-crosslinked polymeric micelles offer a design idea for practicable drug delivery system in cancer therapy.

Antibody-based drug delivery systems for cancer therapy: Mechanisms, challenges, and prospects.

In recent years, antibody-based cancer therapy has emerged as one of the efficient therapeutic strategies, such as immune checkpoint inhibitors (ICIs), angiogenesis inhibitors, antibody-drug conjugates (ADCs), multi-specific antibodies, and chimeric antigen receptor T (CAR-T) cells, among others. To date, various drug delivery platforms have been developed to improve the bioavailability, delivery convenience, and reduced toxicity towards increased therapeutic efficacy of antibodies. Herein, we emphasize the clinical manifestations of various antibody-based tumor therapies, highlighting their mechanisms and applications for cancer therapy. Further, based on the problems to be solved in the current clinical application of antibodies, and combined with the advanced drug delivery technologies, we discuss the roles of antibody-based drug delivery systems (DDSs) in cancer therapy, such as enhanced patient compliance and regulating the tumor microenvironment for combined therapy. By expounding the importance of DDSs and discussing the challenges and prospects of their implementation, we suggest that pharmaceutical enterprises and scientists develop appropriate antibody-based delivery platforms.

Mitochondrion-targeted supramolecular "nano-boat" simultaneously inhibiting dual energy metabolism for tumor selective and synergistic chemo-radiotherapy.

Rationale: Tumor energy metabolism has been a well-appreciated target of cancer therapy; however, the metabolism change of cancer cells between oxidative phosphorylation and glycolysis poses a challenge to the above. In this study, we constructed an innovative mitochondrion-targeted supramolecular “nano-boat” based on peptide self-assembly for tumor combined chemo-radiotherapy by simultaneously inhibiting the dual energy metabolism.Methods: A lipophilic self-assembled peptide and a positively charged cyclen were integrated to fabricate a brand new mitochondrion-targeted nano-platform for the first time. The indices of mitochondrial dysfunction including mitochondrial membrane potential, apoptosis proteins expression and ultrastructure change were evaluated using a JC-1 probe, western blotting and biological transmission electron microscopy, respectively. Energy metabolism assays were conducted on a Seahorse XF24 system by detecting the oxygen consumption rate and the glycolytic proton efflux rate. The radio-sensitization effect was investigated by colony formation, the comet assay, and γ-H2AX staining.Results: The supramolecular “nano-boat” could selectively kill cancer cells by much higher enrichment and reactive oxygen species generation than those in normal cells. In the cancer cells treated with the supramolecular “nano-boat”, the dysfunctional morphological changes of the mitochondrial ultrastructure including swelling and pyknosis were evidently observed, and the endogenous mitochondrial apoptosis pathway was effectively triggered by abundant of cytochrome C leaking out. Concurrently, the dual metabolic pathways of glycolysis and oxidative phosphorylation were severely inhibited. More importantly, the supramolecular “nano-boat” displayed an excellent radio-sensitization effect with a sensitization enhancement ratio value as high as 2.58, and hence, in vivo efficiently combining radiotherapy yielded an enhanced chemo-radiotherapy effect.Conclusion: Our study demonstrated that the rationally designed peptide-based “nano-boat” could efficiently induce cancer cell apoptosis by the energy metabolism inhibition involving multiple pathways, which may provide the motivation for designing novel and universal mitochondria-targeted drug delivery systems for cancer therapy.

The impact of MOFs in pH-dependent drug delivery systems: progress in the last decade.

Metal-organic frameworks (MOFs) are porous crystalline materials consisting of one-, two-, or three-dimensional networks created by metal ions/clusters and multidentate organic linkers through coordination bonding. MOFs are one of the most favorable candidates for biological applications such as wound dressings, cardiac prosthesis, tissue engineering, bioimaging, and drug delivery and as cancer theranostic systems due to their high surface area and porosity for the high loading of therapeutic agents and facile modification of their physical (e.g., pore size and shape) and chemical properties. Drug delivery involves the administration of drugs using a suitable carrier for achieving treatment without unwanted side effects. In the last few years, several types of MOFs have been synthesized including Zn-based MOFs, MIL series MOFs, and Zr-based MOFs and evaluated for their use in different biomedical fields, especially drug delivery. After Fe, zinc is the second most available element in the body, and hence Zn-based MOFs can be considered enduring platforms for various biomedical uses, especially drug delivery applications. MIL series composites and Zr-based biomaterials are also suggested for several biomedical applications due to their good mechanical properties, biocompatibility, and bioactivity. This review highlights the different types of Zn-based and MIL series MOFs that have been used as suitable pH-responsive drug delivery systems and summarizes the Zr-based MOFs that have been used as suitable pH-responsive or reverse pH-responsive drug delivery systems and also discuss their drug-releasing phenomenon at different pH ranges.

A New Approach for beta-cyclodextrin Conjugated Drug Delivery System in Cancer Therapy

A New Approach for beta-cyclodextrin Conjugated Drug Delivery System in Cancer Therapy

A bioinspired stimuli-responsive amino acid-based antibacterial drug delivery system in cancer therapy

Design of tyrosine based stimuli responsive antibacterial drug delivery system with potential application in cancer therapy.

Engineered microorganism-based delivery systems for targeted cancer therapy: a narrative review.

Microorganisms with innate and artificial advantages have been regarded as intelligent drug delivery systems for cancer therapy with the help of engineering technology. Although numerous studies have confirmed the promising prospects of microorganisms in cancer, several problems such as immunogenicity and toxicity should be addressed before further clinical applications. This review aims to investigate the development of engineered microorganism-based delivery systems for targeted cancer therapy. The main types of microorganisms such as bacteria, viruses, fungi, microalgae, and their components and characteristics are introduced in detail. Moreover, the engineering strategies and biomaterials design of microorganisms are further discussed. Most importantly, we discuss the innovative attempts and therapeutic effects of engineered microorganisms in cancer. Taken together, engineered microorganism-based delivery systems hold tremendous promise for biomedical applications in targeted cancer therapy.

Overcoming MDR by Associating Doxorubicin and pH-Sensitive PLGA Nanoparticles Containing a Novel Organoselenium Compound-An In Vitro Study.

In this study, we developed PLGA nanoparticles (NPs) as an effective carrier for 5′-Se-(phenyl)-3-(amino)-thymidine (ACAT-Se), an organoselenium compound, nucleoside analogue that showed promising antitumor activity in vitro. The PLGA NPs were prepared by the nanoprecipitation method and modified with a pH-responsive lysine-based surfactant (77KL). The ACAT-Se-PLGA-77KL-NPs presented nanometric size (around 120 nm), polydispersity index values < 0.20 and negative zeta potential values. The nanoencapsulation of ACAT-Se increased its antioxidant (DPPH and ABTS assays) and antitumor activity in MCF-7 tumor cells. Hemolysis study indicated that ACAT-Se-PLGA-77KL-NPs are hemocompatible and that 77KL provided a pH-sensitive membranolytic behavior to the NPs. The NPs did not induce cytotoxic effects on the nontumor cell line 3T3, suggesting its selectivity for the tumor cells. Moreover, the in vitro antiproliferative activity of NPs was evaluated in association with the antitumor drug doxorubicin. This combination result in synergistic effect in sensitive (MCF-7) and resistant (NCI/ADR-RES) tumor cells, being especially able to successfully sensitize the MDR cells. The obtained results suggested that the proposed ACAT-Se-loaded NPs are a promising delivery system for cancer therapy, especially associated with doxorubicin.

Multifunctional ZnCo2O4 Quantum Dots Encapsulated In Carbon Carrier for Anchoring/Catalyzing Polysulfides and Self‐Repairing Lithium Metal Anode in Lithium‐Sulfur Batteries

AbstractLithium‐sulfur batteries have recently attracted academic/industrial attention due to the high theoretical energy density. However, the capacity decay mainly caused by the polysulfides shuttle effect and poor conductivity of sulfur. Herein, in situ growth of ZnCo2O4 quantum dots (ZCO‐QDs) embedded into the hollow carbon‐carrier sphere (HCS) to form the ZnCo2O4 quantum dots nanocapsule (ZCO‐QDs@HCS) as the multifunctional sulfur host is rationally demonstrated. Based on density‐functional theory calculations, in situ spectroscopic techniques, and electrochemical studies, the synergistic effects on anchoring/catalyzing polysulfide of the ZCO‐QDs@HCS composite in Li‐S batteries is investigated. Interestingly, the ZCO‐QDs@HCS also allows for the controlled release of ZCO‐QDs into the Li‐S electrolyte. Subsequently, it is first discovered that these diffused ZCO‐QDs can act as self‐repairing initiators to stabilize Li metal anodes via rebuilding the damaged solid electrolyte interphase and suppressing Li dendrites growth. With this concept, quantum dots‐based catalyst delivery systems is first constructed in a Li‐S battery, which is similar to the use of nanocarrier‐based drug delivery systems in cancer therapy. The Li‐S cells with the S@ZCO‐QDs@HCS cathode display significantly superior electrochemical performances with a high specific capacity (1350.5 mAh·g−1 at 0.1 C) and excellent cycling stability (capacity decay rate of 0.057% per cycle after 1000 cycles at 3.0 C).

Multi-stimuli-sensitive superparamagnetic κ-carrageenan based nanoparticles for controlled 5-fluorouracil delivery

Herein, a novel multi-stimuli-sensitive nanoparticles with triple magnetic field, temperature, and pH-sensitive features was designed and developed as a drug nanocarrier for delivery of 5-fluorouracil (FL). For this purpose, dimethylaminoethyl methacrylate (DMA) was firstly grafted onto κ-carrageenan (κ-CG), and then κ-CG-g-PDMA copolymer was coated onto Fe3O4 nanoparticles via microwave-supported coprecipitation method. The prepared multi-functional magnetic nanoparticles were characterized by UV, FTIR, XRD, TEM, Zeta-sizer, and VSM analyses to confirm the formation of superparamagnetic Fe3O4@κ-CG-g-PDMA structure. The in vitro FL release of the nanoparticles was investigated at 48 and 37 °C in different pH conditions and exhibited good pH- and temperature-sensitive behavior. Furthermore, the effects of graft yield and magnetic field on FL release were explored. When the magnetic field was applied at 100 kHz, the release of FL increased rapidly, demonstrating that nanoparticles had magnetic field-sensitive features. According to the results, the designed Fe3O4@κ-CG-g-PDMA@FL nanoparticles can be considered as a “smart” drug delivery system for cancer therapy due to its high entrapment efficiency, slow and multi-stimuli-triggered FL release performance, and satisfactory magnetic properties.

An Efficient Carbon-Based Drug Delivery System for Cancer Therapy through the Nucleus Targeting and Mitochondria Mediated Apoptotic Pathway.

The emergence of nanocarriers solves the problems of antitumor drugs such as non-targeting, huge side effects, etc., and has been widely used in tumor therapy. Some kinds of antitumor drugs such as doxorubicin (DOX) mainly act on the nucleic acid causing DNA damage, interfering with transcription, and thereby disrupting or blocking the process of cancer cell replication. Herein, a new nanodrug delivery system, the carbon-based nanomaterials (CBNs)-Pluronic F127-DOX (CPD), is designed by using CBNs as a nanocarrier for DOX. As a result, the tumor growth inhibition rate of CPD group is as high as 79.42± 2.83%, and greatly reduces the side effects. The targeting rate of the CPD group of DOX in the tumor nucleus is 36.78%, and the %ID/g in tumor tissue is 30.09%. The CPD regulates the expression levels of Caspase-3, p53, and Bcl-2 genes by increasing intracellular reactive oxygen species (ROS) levels and reducing mitochondrial membrane potential, which indicates that mitochondrial-mediated pathways are involved in apoptosis. The CPD nanodrug delivery system increases the effective accumulation of DOX in tumor cell nuclei and tumor tissues, and generates massive ROS, thereby inhibiting tumor growth in vivo, representing a promising agent for anticancer applications.

MOF Hydrogel With Structurally Dynamic Properties as Stimuli-Responsive Localized Drug Delivery System for Cancer Therapy

Metal-organic framework (MOF) is an exciting class of porous biomaterial that have been considered as carrier to store and deliver therapeutic drugs. However, pure MOF similar with other nanomaterial is still limitedly used in clinic because of premature diffusion of their payloads and tissue off-targeting behavior. To figure out above challenges, we design a MOF hydrogel with structurally dynamic properties, i.e. self-healing and shear-thinning, as injectable localized drug delivery platform. To realize the presented drug encapsulating hydrogel, the doxorubicin loaded MOF (MOF@DOX) suspension is mixed with home-made bisphosphonate modified hyaluronic acid (HA-BP) polymeric binder. The dynamic coordination bonds basing hydrogel cross-linkage between the bisphosphonate groups on HA-BP macromolecule and the zinc ion on MOF particle affords the hydrogel of injectable, shear-thinning, self-healing properties. HA-BP•MOF@DOX hydrogel demonstrates pH- and ATP-responsive drug release characteristic and kills cancer cells in vitro efficiently. The animal experiments reveal HA-BP•MOF@DOX hydrogel of enhanced capability in terms of suppression tumor growth comparing with MOF@DOX group, which can be caused by the drug localization in hydrogel superstructure and sustainable release at tumor site. Therefore, the presented injectable dynamic MOF hydrogel is a promising in vivo localized drug delivery system for cancer treatment.

Systemic and Local Silk-Based Drug Delivery Systems for Cancer Therapy.

Simple SummaryApplication of drug delivery systems (DDS) in oncology may increase the effectiveness of cancer treatment and reduce the associated adverse side effects. Although various biomaterials can be considered for the development of DDS, the materials of natural origin offer great biocompatibility and degradability. Silk is a natural biomaterial with exceptional properties, and one of them is the possibility to form diverse morphological structures. Scaffolds, films, hydrogels, fibers, foams spheres, capsules, microneedles, among others, can be used for local and systemic drug delivery. In this review, we described the various silk-based DDS for potential application in oncology. However, the unique silk properties combined with the possibility of their further modifications and blending open the gate to numerous potential biomedical applications, not only in the oncology field.For years, surgery, radiotherapy, and chemotherapy have been the gold standards to treat cancer, although continuing research has sought a more effective approach. While advances can be seen in the development of anticancer drugs, the tools that can improve their delivery remain a challenge. As anticancer drugs can affect the entire body, the control of their distribution is desirable to prevent systemic toxicity. The application of a suitable drug delivery platform may resolve this problem. Among other materials, silks offer many advantageous properties, including biodegradability, biocompatibility, and the possibility of obtaining a variety of morphological structures. These characteristics allow the exploration of silk for biomedical applications and as a platform for drug delivery. We have reviewed silk structures that can be used for local and systemic drug delivery for use in cancer therapy. After a short description of the most studied silks, we discuss the advantages of using silk for drug delivery. The tables summarize the descriptions of silk structures for the local and systemic transport of anticancer drugs. The most popular techniques for silk particle preparation are presented. Further prospects for using silk as a drug carrier are considered. The application of various silk biomaterials can improve cancer treatment by the controllable delivery of chemotherapeutics, immunotherapeutics, photosensitizers, hormones, nucleotherapeutics, targeted therapeutics (e.g., kinase inhibitors), and inorganic nanoparticles, among others.

A Review on Nanocarriers Third Generation As Targeted Delivery Systems for Cancer Therapy

Cancer is a leading cause of death worldwide. Currently available therapies are inadequate and spur demand for improved technologies. Nanomaterials are at the cutting edge of the rapidly developing area of nanotechnology. The potential for nanoparticles in cancer drug delivery is infinite with novel new applications constantly being explored. Targeted nanoparticles play a very significant role in cancer drug delivery. The promising implications of these platforms for advances in cancer diagnostics and therapeutics form the basis of this review. Targeted delivery systems of nano biomaterials are necessary to be developed for the diagnosis and treatment of cancer. Nano-based pharmaceuticals, or nanomedicines,” are engineered to either function as a drug or carry a drug while addressing these scientific challenges due to their nano-size. Keywords: Nanomaterials, nanomedicines, Targeted delivery

Paclitaxel nano-conjugated to polyhedral oligomeric silsesquioxane (POSS) nanoparticles as a novel water-soluble prodrug

Condensed polyhedral oligomeric silsesquioxane (POSS) family of materials are very attractive as a nanoscale drug delivery system in cancer therapy. This work describes a novel method for conjugation of poorly soluble anticancer drug paclitaxel (PTX) to octa-aminopropyl polyhedral oligomeric silsesquioxane hydrochloride salt nanoparticles (OA-POSS NPs). The synthesized nanoconjugate of PTX and OA-POSS NPs (PTXn-OA-POSS8-n prodrug) was fully soluble in aqueous solution as compared to the free PTX.

Synthesis of folic acid-conjugated glycodendrimer with magnetic β-cyclodextrin core as a pH-responsive system for tumor-targeted co-delivery of doxorubicin and curcumin

One of the most important applications of nanotechnology in cancer treatment involves the design of magnetic nanocomposites for the targeted delivery of anticancer drugs to cancer cells. This study aims to develop a novel, appropriate, and efficient magnetic carrier having antioxidant properties for the controlled release of anticancer drugs, hydrophilic doxorubicin (DOX), and hydrophobic curcumin (CUR) to cancer cells using folic acid conjugated with magnetic glycodendrimer (Fe 3 O 4 -β-CD-CTD-FA). The synthesized carrier was characterized using DLS, EDX, XRD, BET, FT‐IR, Zeta potential, VSM, TEM, and SEM analysis. The TEM results showed that synthesized Fe 3 O 4 -β-CD-CTD-FA have a spherical-like core-shell structure with an average diameter of approximately 533 nm. The encapsulation efficiency (EE) of Fe 3 O 4 -β-CD-CTD-FA was found to be 98.96% for DOX and 70.91% for CUR. The release studies of DOX and CUR from Fe 3 O 4 -β-CD-CTD-FA showed that maximum release occurs at pH 5 which means it has a controlled pH-responsive behavior. In vitro cytotoxicity and confocal microscopy of the as-synthesized Fe 3 O 4 -β-CD-CTD-FA in MDA-MB-231 cells clearly showed that the prepared carrier had no significant cytotoxicity and could easily enter the cell. Furthermore, the in vitro antioxidant capacity of Fe 3 O 4 -β-CD-CTD-FA was evaluated by DPPH assay and the results exhibited that the synthesized carrier has excellent antioxidant activity (75.45%). Therefore, the obtained glycodendrimer in this study due to their target ability under a magnetic field, excellent biocompatibility, good colloidal stability, simple preparing method, and good antioxidant activity could be used as a promising targeted co-drug delivery system for cancer therapy. • Fe 3 O 4 -β-CD-CTD-FA nanocomposite with antioxidant properties successfully prepared. • The resulted nanocomposite was applied for co-delivery of DOX and CUR to breast cancer cells. • In vitro cytotoxicity and confocal microscopy illustrated that the nanocomposite had no significant cytotoxicity and could easily enter the cells.