Drug Carrier For Cancer Therapy Research Articles

Clinical significance of small extracellular vesicles in cholangiocarcinoma.

Cholangiocarcinoma is an aggressive and heterogeneous malignancy originating from the bile duct epithelium. It is associated with poor prognosis and high mortality. The global incidence of cholangiocarcinoma is rising, and there is an urgent need for effective early diagnosis and treatment strategies to reduce the burden of this devastating tumor. Small extracellular vesicles, including exosomes and microparticles, are nanoscale vesicles formed by membranes that are released both normally and pathologically from cells, mediating the intercellular transfer of substances and information. Recent studies have demonstrated the involvement of small extracellular vesicles in numerous biological processes, as well as the proliferation, invasion, and metastasis of tumor cells. The present review summarizes the tumorigenic roles of small extracellular vesicles in the cholangiocarcinoma microenvironment. Owing to their unique composition, accessibility, and stability in biological fluids, small extracellular vesicles have emerged as ideal biomarkers for use in liquid biopsies for diagnosing and outcome prediction of cholangiocarcinoma. Specific tissue tropism, theoretical biocompatibility, low clearance, and strong biological barrier penetration of small extracellular vesicles make them suitable drug carriers for cancer therapy. Furthermore, the potential value of small extracellular vesicle-based therapies for cholangiocarcinoma is also reviewed.

Synthesis of High-Precision Sub-Micron CaCO3 Anticancer Drug Carriers from Coral Remains

Calcium carbonate (CaCO3) particles have attracted increasing attention as a promising material for drug delivery systems. In this study, coral remains were utilized as a raw material for a novel drug carrier. A series of pre-treatment and parameter experiments were conducted to synthesize sub-micron spherical CaCO3 particles. The CaCO3 particles exhibited uniform size distribution, with the minimum mean size being only 344 nm. The effects on the CaCO3 crystal phases and particle sizes were also discussed in this study. Drug loading experiments were also conducted to assess the feasibility of the CaCO3 drug carrier. We loaded TRITC-Dextran into CaCO3 particles for the simulation experiments. The loading capacity reached up to 9.6 wt.%, which was as high as common drug carriers such as liposomes. In this study, we aimed not only to tackle the local environmental issues caused by coral remains, but also to synthesize a suitable drug carrier for cancer therapy using the outstanding properties and low cost of CaCO3.

MAb-Functionalized Biomimetic MamC-Mediated-Magnetoliposomes as Drug Delivery Systems for Cancer Therapy.

In cancer therapy, new therapeutic nanoformulations able to mediate targeted chemotherapy are required. Recently, biomimetic magnetic nanoparticles (BMNPs) mediated by MamC, a magnetosome protein from Magnetococcus marinus MC-1, have proven, in vitro and in vivo, to be effective drug nanocarriers (following the application of an external gradient magnetic field) and to allow combination with hyperthermia. However, these nanoassemblies require further optimization to improve cytocompatibility, stability and active targeting ability. Herein, we describe the production of the magnetoliposomes (LP) embedding BMNPs functionalized (or not) with doxorubicin (DOXO), [LP(+/-DOXO-BMNPs)], and their surface modification with the DO-24 mAb, which targets the human Met/HGF receptor's ectodomain (overexpressed in many cancers). Nanoformulations were extensively characterized using TEM, DLS, FTIR and when tested in vitro, the lipid coating increased the colloidal stability and their biocompatibility, favoring the cellular uptake in cells overexpressing the cognate receptor. Indeed, the magnetoliposomes mAb-LP(+/-DOXO-BMNPs) exerted a specific active targeting ability by the presence of the mAb that preserved its immunocompetence. Both LP(BMNPs) and mAb-LP(BMNPs) were not toxic to cells, while +/-mAb-LP(DOXO-BMNPs) nanoformulations were indeed cytotoxic. Therefore, this study represents a proof of concept for the development of promising drug carriers for cancer therapy based on local chemotherapy directed by mAbs.

Temozolomide and flavonoids against glioma: from absorption and metabolism to exosomal delivery.

Patients with glioblastoma multiforme and anaplastic astrocytoma are treated with temozolomide. Although it has been demonstrated that temozolomide increases GBM patient survival, it has also been connected to negative immune-related adverse effects. Numerous research investigations have shown that flavonoids have strong antioxidant and chemo-preventive effects. Consequently, it might lessen chemotherapeutic medicines' side effects while also increasing therapeutic effectiveness. The need for creating innovative, secure, and efficient drug carriers for cancer therapy has increased over time. Recent research indicates that exosomes have enormous potential to serve as carriers and cutting-edge drug delivery systems to the target cell. In recent years, researchers have been paying considerable attention to exosomes because of their favorable biodistribution, biocompatibility, and low immunogenicity. In the present review, the mechanistic information of the anti-glioblastoma effects of temozolomide and flavonoids coupled with their exosomal delivery to the targeted cell has been discussed. In addition, we discuss the safety aspects of temozolomide and flavonoids against glioma. The in-depth information of temozolomide and flavonoids action via exosomal delivery can unravel novel strategies to target Glioma.

Development of a Smart Portable Hypoxic Chamber with Accurate Sensing, Control and Visualization of In Vitro Cell Culture for Replication of Cancer Microenvironment.

Clinical resistance towards treatment is a major concern in cancer therapy. This is due to in vitro studies lacking essential microenvironmental aspects. Tumor-hypoxia is an important pathophysiological phenomenon in numerous malignant tumors. Various studies have shown the importance of a hypoxic microenvironment (HME) in cancer drug resistance and its effects on cellular signaling and metabolism pathways. Most drugs fail in transition from a laboratory to clinical trials because of the variability in the testing microenvironment conditions. It is, thus, very crucial that research work needs to replicate these conditions in vitro to test the drugs and/or drug carriers for cancer therapy. Previous works have used a portable hypoxia chamber to reduce the cell microenvironment to hypoxic conditions. These techniques lack reliability and consistency due to a lack of control and visualization. In this research, we developed a smart portable hypoxia chamber that could accurately control the oxygen inside the portable chamber and have a global visualization. The proposed hypoxia chamber provided ease of use with the ranges of 1% to 20% oxygen with increments of 0.5%, as well as reproducibility and accuracy. The chamber displayed great precision on reaching the set oxygen limit and a high stability in maintaining that set level of oxygen compared to the uncontrolled setup for extended durations (24 h). For instance, at a 2% oxygen level, our automated system maintained this level over 1400 min, whereas the oxygen level fluctuated up to 4.5% in the conventional hypoxic chamber. We have also demonstrated the pitfalls of uncontrolled and non-visualized hypoxia chamber setup and the dire need for our system. The hypoxia-induced factor (HIF-1α) expression in cancer cell lines was tested and compared between the conventional hypoxia setup and our automated hypoxia chamber. We observed that there was a twofold increase in HIF-1α expression in the automated controlled chamber compared to the conventional device. The device also provided real-time sensing, visualization and control of the chamber conditions, which could aid in complex in vitro studies.

Recent Progress in Extracellular Vesicle-Based Carriers for Targeted Drug Delivery in Cancer Therapy.

Extracellular vesicles (EVs) are small, membrane-based vesicles released by cells that play a critical role in various physiological and pathological processes. They act as vehicles for transporting a variety of endogenous cargo molecules, enabling intercellular communication. Due to their natural properties, EVs have emerged as a promising "cell-free therapy" strategy for treating various diseases, including cancer. They serve as excellent carriers for different therapeutics, including nucleic acids, proteins, small molecules, and other nanomaterials. Modifying or engineering EVs can improve the efficacy, targeting, specificity, and biocompatibility of EV-based therapeutics for cancer therapy. In this review, we comprehensively outline the biogenesis, isolation, and methodologies of EVs, as well as their biological functions. We then focus on specific applications of EVs as drug carriers in cancer therapy by citing prominent recent studies. Additionally, we discuss the opportunities and challenges for using EVs as pharmaceutical drug delivery vehicles. Ultimately, we aim to provide theoretical and technical support for the development of EV-based carriers for cancer treatment.

Nano-liposomes: Historical Perspectives and Major Advances in Cancer Therapy. A critical Review

Since the discoveryof liposomes by Bangham and co-workers in 1960, giant strides in the field ofliposomes as drug carriers for cancer therapy have been achieved. From the veryfirst generation of liposomes known as conventional liposomes to the stealthliposomes which are surface decorated with polyethylene glycol attachments toprotect the liposomes from phagocytic attack, and finally, a more recent nano-liposomedelivery innovation which involves specific antibody targeting and stimulussensitivity. Advanced research on enhancing the stability of liposomes throughvarious smart surface modifications has been ongoing. Some liposomalformulations have made it from benchtop research to pharmaceuticalmanufacturing and marketing. Commercially available are stealth liposomeformulations which have been approved for use, including Doxil® (a PEGylatedliposomal formulation of doxorubicin hydrochloride). These formulations haveshown increased bioavailability at the target site compared to conventionaldrugs.

Micro/nanomotor: A promising drug delivery system for cancer therapy

Micro/nanomotors (MNMs) are small-scale devices that can effectively convert various forms of energy into mechanical motion. Their controllable motility and good permeability have attracted the interest of researchers as promising drug carriers in cancer therapy. Compared with traditional formulations, micro/nanomotor drug delivery systems can greatly improve therapeutic efficiency and reduce the side effects of antitumor drugs. This review mainly discusses the advantages of micro/nanomotor drug delivery systems and the applications of MNMs propelled by exogenous, endogenous, and biohybrid power in cancer therapy. Finally, the main challenges of the applications of micro/nanomotor drug delivery systems, as well as future development trends and opportunities are discussed.

The Potential Use of Exosomes in Anti-Cancer Effect Induced by Polarized Macrophages.

The rapid development of aberrant cells outgrowing their normal bounds, which can subsequently infect other body parts and spread to other organs-a process known as metastasis-is one of the significant characteristics of cancer. The main reason why cancer patients die is because of widespread metastases. This abnormal cell proliferation varies in cancers of over a hundred types, and their response to treatment can vary substantially. Several anti-cancer drugs have been discovered to treat various tumors, yet they still have harmful side-effects. Finding novel, highly efficient targeted therapies based on modifications in the molecular biology of tumor cells is essential to reduce the indiscriminate destruction of healthy cells. Exosomes, an extracellular vesicle, are promising as a drug carrier for cancer therapy due to their good tolerance in the body. In addition, the tumor microenvironment is a potential target to regulate in cancer treatment. Therefore, macrophages are polarized toward M1 and M2 phenotypes, which are involved in cancer proliferation and are malignant. It is evident from recent studies that controlled macrophage polarization might contribute to cancer treatment, by the direct way of using miRNA. This review provides an insight into the potential use of exosomes to develop an 'indirect', more natural, and harmless cancer treatment through regulating macrophage polarization.

Supermolecule-Drug Conjugates Based on Acid-Degradable Polyrotaxanes for pH-Dependent Intracellular Release of Doxorubicin.

Doxorubicin (DOX)-conjugated acid-degradable polyrotaxanes (PRXs) were designed as supramolecular drug carriers capable of releasing drugs in acidic cellular environments. Acid-degradable PRXs composed of α-cyclodextrin (α-CD) as a cyclic molecule, poly(ethylene glycol) (PEG) as a polymer axis, and N-triphenylmethyl (N-Trt) groups as an acid-labile stopper molecules were synthesized and DOX was conjugated with the threaded α-CDs in the PRXs. Because the acid-induced cleavage of N-Trt groups in PRXs leads to PRX dissociation, the DOX-modified α-CDs were released under acidic conditions (pH 5.0). The cytotoxicity of DOX-conjugated PRXs in colon-26 cells revealed significant cell death for DOX-conjugated PRXs after 48 h of treatment. Confocal laser scanning microscopy (CLSM) analysis revealed that the fluorescence signals derived from DOX-conjugated PRXs were observed in cellular nuclei after 48 h, suggesting that the DOX-modified α-CDs were released and accumulated in cellular nuclei. These results confirmed that acid-degradable PRXs can be utilized as drug carriers capable of releasing drug-modified α-CDs in acidic lysosomes and eliciting cytotoxicity. Overall, acid-degradable PRXs represent a promising supramolecular framework for the delivery and intracellular release of drug-modified α-CDs, and PRX-drug conjugates are expected to contribute to the development of pH-responsive drug carriers for cancer therapy.

Therapeutic poly(amino acid)s as drug carriers for cancer therapy

As one of the top global health problems, the effective treatment of cancer is one of the most urgent clinical challenges. Currently, the main treatments for cancer include surgery, chemotherapy, radiotherapy, and gene therapy etc. Chemotherapy is one of the most commonly used treatments, however it has limitations such as highly toxic side effects and low drug utilization rate that limit its application. Gene therapy, as an emerging cancer treatment, has limitations such as drug instability, off-target effects and low internalization efficiency. Poly(amino acid)s carriers with good biocompatibility, degradability and multifunctionality as drug carriers have received much attention, as they can reduce the toxic side effects of chemotherapy, improve drug utilization, and enhance the internalization efficiency and utilization of gene drugs. However, little attention has been paid to the nature of the carriers themselves. This paper reviews the immunomodulatory, anti-inflammatory, antioxidant, internalization-promoting and apoptosis-promoting functions of poly(amino acid)s drug carriers in tumor therapy to provide a theoretical basis for different carrier-drug-adapted synergistic therapies.

Effect of calcination temperature on structural, antibacterial, radiation shielding and magnetic properties of cubic spinel cobalt nanoferrite

For the first time, Cobalt ferrite (CoFO) nanoparticles (NPs) were synthesized by solution combustion method using BigThyme leaf extract as a reducing agent followed by varying the calcination temperature as-formed — 800 °C. At all the calcination temperatures, Bragg reflections matches well with FCC cubic spinel structure. Crystallite size increases from 12–79 nm with increase in calcination temperature. The SAED pattern and d-spacing from Transmission electron microscopy matches well with the PXRD pattern and the calculated crystallite size matches well with the Scherrer’s formula. The direct energy band gap was found to be 1.55 eV. The effect of calcination temperature on different magnetic properties such as retentivity, coercivity, saturation of magnetization, squareness ratio and Bohr magneton was discussed in detail. Large coercivity (2.26 kOe) is observed at low calcination temperature. Further, X-ray/gamma radiation absorption parameters such as mass attenuation coefficient, half value layer and Zeff are established which is an essential in the field of radiation dosimetry. CoFO NPs exhibited sensitivity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The cytotoxic properties were examined on cervical cancer HeLa cells and compared with the cisplatin drug. CoFO NPs shows higher % cell viability and less % cell death. Thus, CoFO NPs can be used as a drug carrier in cancer therapy.

Enhanced photothermal heating and combination therapy of gold nanoparticles on a breast cell model

Multi-drug resistance (MDR) in addition to the damage to non-malignant normal cells are the most difficult in cancer treatment. Drug delivery and Plasmonic photothermal therapy based on the use of resonant metallic nanoparticles have developed as promising techniques to destroy cancer cells selectively. In the present work, gold nanoparticles (AuNPs) were synthesized using trisodium citrate. The prepared AuNPs have a small size of 14 ± 4 nm and exhibit high stability with Zeta potential − 18 mV, AuNPs showed higher photothermal heating efficiency compared to irradiation with a 532 nm laser alone on the breast cancer cell line (MCF-7). Treatment of MCF-7 cells with 0.125 mM AuNPs coupled with laser irradiation for 6 min was found to significantly reduce (34%) the cell viability compared to 5% obtained with AuNPs in the same concentration and 26% with laser irradiation for 6 min without AuNPs. Moreover, the prepared AuNPs were used as an anticancer drug carrier for Doxorubicin (Dox), upon loading Dox to AuNPs there was a slight increase in the particle size to 16 ± 2 nm, FT-IR spectroscopic results showing the binding of Dox to AuNPs was through the –NH group. The potential cytotoxicity of the DOX@AuNPs nanocomposite was significantly increased compared to free DOX on the MCF7 cell line with a decrease in IC50. All these results suggested the potential use of AuNPs as therapeutic photothermal agents and drug carriers in cancer therapy.

Mannosylated poly(acrylic acid)-coated mesoporous silica nanoparticles for anticancer therapy

Although mesoporous silica nanoparticles (MSNs) are widely used as anticancer drug carriers, unmodified MSNs induce off-target effects and at high doses, there are adverse effects of hemolysis because of the interaction with the silanol group on the surface and cells. In this study, we developed doxorubicin (DOX)-loaded MSNs coated with mannose grafted poly (acrylic acid) copolymer (DOX@MSNs-man-g-PAA) to enhance the hemocompatibility and target efficacy to cancer cells. This uniform nanosized DOX@MSNs-man-g-PAA showed sustained and pH-dependent drug release with improved hemocompatibility over the bare MSNs. The uptake of the DOX@MSN-man-g-PAA in breast cancer cells was significantly improved by mannose receptor-mediated endocytosis, which showed significant increasing intracellular ROS and changes in mitochondrial membrane potential. This formulation exhibited superior tumor-suppressing activity in the MDA-MB-231 cells inoculated mice. Overall, the present study suggested the possibility of the copolymer-coated MSNs as drug carriers for cancer therapy.

One‐Pot Synthesis of Size‐Controlled Poly(cyclotriphosphazene‐co‐hesperetin) Microspheres and Their Properties as Drug Delivery Carriers

AbstractIn this study, cross‐linked poly(cyclotriphosphazene‐co‐hesperetin) (PCTPHP) microspheres were synthesized by the reaction of hexachlorocyclotriphosphazene (HCCP) with hesperetin (HSP). Fourier transform infrared (FT‐IR) spectroscopy was used to confirm the successful preparation of the PCTPHP microspheres. The cross‐linking density of the prepared PCTPHP microspheres was examined by electron paramagnetic resonance (EPR) spectroscopy. The results showed that the increased HSP mole might be more suitable to cross‐link with HCCP in high density. The thermal properties, particle size distribution, morphology and crystalline nature of PCTPHP microspheres were investigated by thermogravimetric analysis (TGA), dynamic light scattering (DLS), scanning electron microscope (SEM) and X‐ray diffraction (XRD). The prepared PCTPHP‐3 microspheres were used as drug carriers. The 5‐fluorouracil (5‐FU) was loaded on the microspheres and their in vitro release behavior was observed at two different pH values. The results showed a controlled release of 5‐FU from the PCTPHP‐3/5‐FU in both basic and acidic mediums up to 216 h. The results showed that the PCTPHP microspheres might play a vital role as drug carriers in cancer therapy.

The Most Recent Discoveries in Heterocyclic Nanoformulations for Targeted Anticancer Therapy.

Every day, new cases of cancer patients whose recovery is delayed by multidrug resistance and chemotherapy side effects are identified, which severely limit treatment options. One of the most recent advances in nanotechnology is the effective usage of nanotechnology as drug carriers for cancer therapy. As a consequence, heterocyclic nanocarriers were put into practice to see whether they could have a better cure with positive results. The potential of a therapeutic agent to meet its desired goal is vital to its success in treating any disease. Heterocyclic moieties are molecules that have a wide variety of chemically therapeutic functions as well as a significant biological activity profile. Heterocyclic nanoformulations play an important role in cell physiology and as possible arbitrators for typical biological reactions, making them valuable in cancer research. As a result, experts are working with heterocyclic nanoformulation to discover alternative approaches to treat cancer. Due to their unique physicochemical properties, heterocyclic compounds are real cornerstones in medicinal chemistry and promising compounds for the future drug delivery system. This review briefly explores the therapeutic relevance of heterocyclic compounds in cancer treatment, various nanoformulation, and actively describes heterocyclic magnetic nano catalysts and heterocyclic moiety, as well as their mode of action, which have favorable anti-cancer effects.

Dendrimer-Functionalized Nanodiamonds as Safe and Efficient Drug Carriers for Cancer Therapy: Nucleus Penetrating Nanoparticles.

Nanodiamonds (NDs) are increasingly being assessed as potential candidates for drug delivery in cancer cells and they hold great promise in overcoming the side effects of traditional chemotherapeutics. In the current work, carboxylic acid functionalized nanodiamonds (ND-COOH) were covalently modified with poly(amidoamine) dendrimer (PAMAM) to form amine-terminated nanodiamonds (NP). Unlike ND-COOH, the chemically modified nanodiamond platform NP revealed a pH-independent aqueous dispersion stability, enhancing its potential as an effective carrier. Physical encapsulation of poorly water soluble cabazitaxel (CTX) drug on NP formed ND-PAMAM-CTX (NPC) nanoconjugates and substantially reduced the size of CTX from micrometer to nanometer. CTX was localized within the pores of nanoparticle aggregates and the cavities of the PAMAM dendrimer, thus facilitating the loaded drug's controlled and sustained release. NPC's cumulative CTX release efficiency was determined to be ∼95% at pH 4 after 96 h. A high cellular uptake of NPC both within the cytoplasm and nucleus of U87 cells is confirmed, accounting for a reduced IC50 value (1 nM). Both the cell cycle and Western blot analyses confirmed enhanced cell death and suppressed tubulin protein expression in NPC-treated cells. A significantly high inhibition to cell division with early apoptosis and reduced metastasis demonstrates the effective loading of CTX dosages on the nanocarrier. The present work highlights the potential of a newly designed nanocarrier NP as an efficient nanocargo for cellular delivery applications and may provide future insights to treat one of the most aggressive tumors in neuro-oncological research, glioblastoma multiforme (GBM).

Manganese Phosphate-Doxorubicin-Based Nanomedicines Using Mimetic Mineralization for Cancer Chemotherapy.

Inorganic nanomaterials showed great potential as drug carriers for chemotherapeutics molecules due to their biocompatible physical and chemical properties. A manganese-based inorganic nanomaterial manganese phosphate (MnP) had become a new drug carrier in cancer therapy. However, the approach for manganese phosphate preparation and drug integration is still confined in complex methods. Inspired by mimetic mineralization, we proposed a "one-step" method for the preparation of manganese phosphate-doxorubicin (DOX) nanomedicines (MnP-DOX) by manganese ion and DOX complexation. The structural characterization results revealed that the prepared MnP-DOX nanocomplexes were homogeneous with controlled sizes and shapes. More importantly, the MnP-DOX nanocomposites could significantly induce cancer inhibition in vitro and in vivo. The results indicated that the drug molecules were integrated into MnP nanocarriers by mimetic mineralization, which not only prevented the premature release of the drug but also reduced excessive modification. Moreover, the designed MnP-DOX complex showed high loading efficacy and pH-dependent degradation leading to drug release, achieving high efficiency for cancer chemotherapy in vitro and in vivo via a facile process. These achievements presented an approach to construct the manganese phosphate-based chemotherapy nanomedicines by mimetic mineralization for cancer therapy.

Synthesis and characterization of mesoporous silica-g-poly(hydroxyethylmethacrylate) nanohybrid particles as a drug delivery system

Hybrid nanoparticles (MSiO2/TMSPMA-g-PHEMA) based on poly(hydroxyethylmethacrylate) (PHEMA) grafted onto mesoporous silica particles (MSiO2) were prepared using “grafting from” approach by free radical polymerization. According to thermogravimetric analysis (TGA), the amount of grafted PHEMA increased as a function of the quantity of monomer feed. The hybrid nanoparticles were uniformly shaped as ellipsoids with a mean size diameter of 74 nm. Textural characterization and transmission electron microscopy (TEM) demonstrated that the morphology and structural framework of the materials were maintained. The grafted PHEMA favored that MSiO2/TMSPMA-g-PHEMA system could be well dispersed in an aqueous solution, showing pH dependence. The hybrid nanoparticles were capable to load 5FU with a maximum efficiency of 36.6% ± 5.4%. The drug release rate of (MSiO2/TMSPMA-g-PHEMA)/5FU was pH dependent and reached up to 86 ± 2.58% after 4 h at pH 7.4, much higher than at pH 2, which was only 46 ± 3.20% in 3.5 h. In vitro cytotoxicity test showed that hybrid MSiO2 were cytotoxic against U87 glioblastoma cells, indicating that the dosage-dependent effect of the hybrid delivery system was more effective than free 5FU. These results suggested that the MSiO2/TMSPMA-g-PHEMA is a potential system to be used as drug carrier 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.