Targeted Delivery of Drugs and Genes Using Polymer Nanocarriers for Cancer Therapy

Cancer is one of the primary causes of worldwide human deaths. Most cancer patients receive chemotherapy and radiotherapy, but these treatments are usually only partially efficacious and lead to a variety of serious side effects. Therefore, it is necessary to develop new therapeutic strategies. The emergence of nanotechnology has had a profound impact on general clinical treatment. The application of nanotechnology has facilitated the development of nano-drug delivery systems (NDDSs) that are highly tumor selective and allow for the slow release of active anticancer drugs. In recent years, vehicles such as liposomes, dendrimers and polymer nanomaterials have been considered promising carriers for tumor-specific drug delivery, reducing toxicity and improving biocompatibility. Among them, polymer nanoparticles (NPs) are one of the most innovative methods of non-invasive drug delivery. Here, we review the application of polymer NPs in drug delivery, gene therapy, and early diagnostics for cancer therapy.     

CRPC Membrane-Camouflaged,Biomimetic Nanosystem for Overcoming Castration-Resistant Prostate Cancer by Cellular Vehicle-Aided Tumor Targeting

Castration-resistant prostate cancer (CRPC) is the most common malignant tumor of the male urinary system. Nanodrug delivery systems (NDDS) have been widely applied in drug delivery for tumor therapy; however, nanotherapeutics encounter various biological barriers that prevent successful accumulation of drugs, specifically at diseased sites. Therefore, there is an urgent need to develop a CRPC-targeting nanocomposite with fine biocompatibility for penetrating various biological barriers, delivering sufficient drugs to the targeting site and improving therapeutic efficiency. In this work, CRPC cell membranes were firstly adapted as biomimetic vectors for the encapsulating PEG−PLGA polymer containing the chemotherapy drug docetaxel (DTX). The CRPC membrane-camouflaged nanoparticles can easily escape early recognition by the immune system, penetrate the extracellular barrier, and evade clearance by the circulatory system. In addition to the characteristics of traditional nanoparticles, the CRPC cell membrane contains an arsenal of highly specific homotypic moieties that can be used to recognize the same cancer cell types and increase the targeted drug delivery of DTX. In vivo fluorescence and radionuclide dual-model imaging were fulfilled by decorating the biomimetic nanosystem with near-infrared dye and isotope, which validated the homotypic targeting property offered by the CRPC cell membrane coating. Importantly, remarkably improved therapeutic efficacy was achieved in a mice model bearing CRPC tumors. This homologous cell membrane enabled an efficient drug delivery strategy and enlightened a new pathway for the clinical application of tumor chemotherapy drugs in the future.     

In vitro Biological Tests as the First Tools To Validate Magnetic Nanotheranostics for Colorectal Cancer Models

Colorectal cancer (CRC) remains a leading cause of cancer death. Nanotechnology has focused on reaching more effective treatments. In this concern, magnetic nanoparticles (MNPs) have been studied for a wide range of biomedical applications related to CRC, such as diagnostic imaging, drug delivery and thermal therapy. However, limited research is currently found in the open literature that refers to nanosystems combining all these mentioned areas (theranostics). When developing nanosystems intended as theranostics applied to CRC, possible variations between patients must be considered. Therefore, multiple in vitro assays are required as guidance for future preclinical and clinical trials. The objective of this contribution is to evaluate the available and recent literature regarding the interactions of MNP and CRC models, aiming to critically analyze the information given by the commonly used assays and evaluate the data provided by each one with a view to implementing this novel technology in CRC diagnostics and therapy.     

Theoretical Analysis for Using Pulsed Heating Power in Magnetic Hyperthermia Therapy of Breast Cancer

In magnetic hyperthermia, magnetic nanoparticles (MNPs) are used to generate heat in an alternating magnetic field to destroy cancerous cells. This field can be continuous or pulsed. Although a large amount of research has been devoted to studying the efficiency and side effects of continuous fields, little attention has been paid to the use of pulsed fields. In this simulation study, Fourier’s law and COMSOL software have been utilized to identify the heating power necessary for treating breast cancer under blood flow and metabolism to obtain the optimized condition among the pulsed powers for thermal ablation. The results showed that for small source diameters (not larger than 4 mm), pulsed powers with high duties were more effective than continuous power. Although by increasing the source domain the fraction of damage caused by continuous power reached the damage caused by the pulsed powers, it affected the healthy tissues more (at least two times greater) than the pulsed powers. Pulsed powers with high duty (0.8 and 0.9) showed the optimized condition and the results have been explained based on the Arrhenius equation. Utilizing the pulsed powers for breast cancer treatment can potentially be an efficient approach for treating breast tumors due to requiring lower heating power and minimizing side effects to the healthy tissues.     

Bioengineered Ferritin Nanocarriers for Cancer Therapy

Ferritin naturally exists in most organisms and can specifically recognize the transferrin 1 receptor (TfR1), which is generally highly expressed on various types of tumor cells. The pH dependent reversible assembling and disassembling property of ferritin renders it as a suitable candidate for encapsulating a variety of anticancer drugs and imaging probes. Ferritins external surface is chemically and genetically modifiable which can serve as attachment site for tumor specific targeting peptides or moieties. Moreover, the biological origin of these protein cages makes it a biocompatible nanocarrier that stabilizes and protects the enclosed particles from the external environment without provoking any toxic or immunogenic responses. Recent studies, further establish ferritin as a multifunctional nanocarrier for targeted cancer chemotherapy and phototherapy. In this review, we introduce the favorable characteristics of ferritin drug carriers, the specific targeted surface modification and a multifunctional nanocarriers combined chemotherapy with phototherapy for tumor treatment. Taken together, ferritin is a potential ideal base of engineered nanoparticles for tumor therapy and still needs to explore more on its way.     

Recent Advances in Preclinical Research Using PAMAM Dendrimers for Cancer Gene Therapy

Carriers of genetic material are divided into vectors of viral and non-viral origin. Viral carriers are already successfully used in experimental gene therapies, but despite advantages such as their high transfection efficiency and the wide knowledge of their practical potential, the remaining disadvantages, namely, their low capacity and complex manufacturing process, based on biological systems, are major limitations prior to their broad implementation in the clinical setting. The application of non-viral carriers in gene therapy is one of the available approaches. Poly(amidoamine) (PAMAM) dendrimers are repetitively branched, three-dimensional molecules, made of amide and amine subunits, possessing unique physiochemical properties. Surface and internal modifications improve their physicochemical properties, enabling the increase in cellular specificity and transfection efficiency and a reduction in cytotoxicity toward healthy cells. During the last 10 years of research on PAMAM dendrimers, three modification strategies have commonly been used: (1) surface modification with functional groups; (2) hybrid vector formation; (3) creation of supramolecular self-assemblies. This review describes and summarizes recent studies exploring the development of PAMAM dendrimers in anticancer gene therapies, evaluating the advantages and disadvantages of the modification approaches and the nanomedicine regulatory issues preventing their translation into the clinical setting, and highlighting important areas for further development and possible steps that seem promising in terms of development of PAMAM as a carrier of genetic material.     

Development of Biodegradable GQDs-hMSNs for Fluorescence Imaging and Dual Cancer Treatment via Photodynamic Therapy and Drug Delivery

Recently, nano-based cancer therapeutics have been researched and developed, with some nanomaterials showing anticancer properties. When it comes to cancer treatment, graphene quantum dots (GQDs) contain the ability to generate ¹O₂, a reactive oxidative species (ROS), allowing for the synergistic imaging and photodynamic therapy (PDT) of cancer. However, due to their small particle size, GQDs struggle to remain in the target area for long periods of time in addition to being poor drug carriers. To address this limitation of GQDs, hollow mesoporous silica nanoparticles (hMSNs) have been extensively researched for drug delivery applications. This project investigates the utilization and combination of biomass-derived GQDs and Stöber silica hMSNs to make graphene quantum dots-hollow mesoporous silica nanoparticles (GQDs-hMSNs) for fluorescent imaging and dual treatment of cancer via drug delivery and photodynamic therapy (PDT). Although the addition of hMSNs made the newly synthesized nanoparticles slightly more toxic at higher concentrations, the GQDs-hMSNs displayed excellent drug delivery using fluorescein (FITC) as a mock drug, and PDT treatment by using the GQDs as a photosensitizer (PS). Additionally, the GQDs retained their fluorescence through the surface binding to hMSNs, allowing them to still be used for cell-labeling applications.     

Redox-Responsive Porphyrin-Based Polysilsesquioxane Nanoparticles for Photodynamic Therapy of Cancer Cells

The development of stimulus-responsive photosensitizer delivery systems that carry a high payload of photosensitizers is of great importance in photodynamic therapy. In this study, redox-responsive polysilsesquioxane nanoparticles (PSilQNPs) built by a reverse microemulsion approach using 5,10,15,20-tetrakis(carboxyphenyl) porphyrin (TCPP) silane derivatives as building blocks, were successfully fabricated. The structural properties of TCPP-PSilQNPs were characterized by dynamic light scattering (DLS)/ζ-potential, scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The photophysical properties were determined by UV-vis and fluorescence spectroscopy. The quantity of singlet oxygen generated in solution was measured using 1,3-diphenylisobenzofuran. The redox-responsive release of TCPP molecules was successfully demonstrated in solution in the presence of a reducing agent. The internalization of TCPP-PSilQNPs in cancer cells was investigated using laser scanning confocal microscopy. Phototoxicity experiments in vitro showed that the redox-responsive TCPP-PSilQNPs exhibited an improved phototherapeutic effect on cervical cancer cells compared to a non-responsive TCPP-PSilQNP control material.     

Efficient Synthesis of a Maghemite/Gold Hybrid Nanoparticle System as a Magnetic Carrier for the Transport of Platinum-Based Metallotherapeutics

The preparation and thorough characterization of a hybrid magnetic carrier system for the possible transport of activated platinum-based anticancer drugs, as demonstrated for cisplatin (cis-[Pt(NH₃)₂Cl₂], CDDP), are described. The final functionalized mag/Au–LA–CDDP* system consists of maghemite/gold nanoparticles (mag/Au) coated by lipoic acid (HLA; LA stands for deprotonated form of lipoic acid) and functionalized by activated cisplatin in the form of cis-[Pt(NH₃)₂(H₂O)₂]²⁺ (CDDP*). The relevant techniques (XPS, EDS, ICP-MS) proved the incorporation of the platinum-containing species on the surface of the studied hybrid system. HRTEM, TEM and SEM images showed the nanoparticles as spherical with an average size of 12 nm, while their superparamagnetic feature was proven by ⁵⁷Fe Mössbauer spectroscopy. In the case of mag/Au, mag/Au–HLA and mag/Au–LA–CDDP*, weaker magnetic interactions among the Fe³⁺ centers of maghemite, as compared to maghemite nanoparticles (mag), were detected, which can be associated with the non-covalent coating of the maghemite surface by gold. The pH and time-dependent stability of the mag/Au–LA–CDDP* system in different media, represented by acetate (pH 5.0), phosphate (pH 7.0) and carbonate (pH 9.0) buffers and connected with the release of the platinum-containing species, showed the ability of CDDP* to be released from the functionalized nanosystem.     

Identification of Lectins from Metastatic Cancer Cells through Magnetic Glyconanoparticles

Cancer cells can have characteristic carbohydrate binding properties. Previously, it was shown that a highly metastatic melanoma cell line B16F10 bound to galactoside-functionalized nanoparticles much stronger than the corresponding less metastatic B16F1 cells. To better understand the carbohydrate binding properties of cancer cells, herein, we report the isolation and characterization of endogenous galactose binding proteins from B16F10 cells using magnetic glyconanoparticles. The galactose-coated magnetic glyconanoparticles could bind with lectins present in the cells and be isolated through magnet-mediated separation. Through Western blot and mass spectrometry, the arginine/serine rich splicing factor Sfrs1 was identified as a galactose-selective endogenous lectin, overexpressed in B16F10 cells, compared with B16F1 cells. In addition, galactin-3 was found in higher amounts in B16F10 cells. Finally, the glyconanoparticles exhibited a superior efficiency in lectin isolation, from both protein mixtures and live cells, than the corresponding more traditional microparticles functionalized with carbohydrates. Thus, the magnetic glyconanoparticles present a useful tool for discovery of endogenous lectins, as well as binding partners of lectins, without prior knowledge of protein identities.     

Pasty Polymers in Cancer Drug Therapy

Injectable polymeric systems suitable for the localized delivery of anticancer agents are reviewed. These polymeric systems include: drug-loaded low melting temperature polymers that are injected at the melting temperature of the polymer, usually below 50 °C, that solidify at body temperature to form an in situ device; polymer solutions in buffer or in N-methyl pyrrolidone, ethanol, or acetate esters which, upon injection in tissue,are absorbed into the tissue and cause precipitation of the polymer at the injection site; in situ crosslinking of polymer solutions to form a polymeric implant; and thermoresponsive polymer solutions that are soluble at room temperature and solidify at body temperature. However, these systems are hydrophilic and suffer from burst release of drug within a few hours post injection. Hydrophobic injectable, pasty, fat-based polymers that gel when injected in tissue have been used for the extended release of paclitaxel, cisplatin, and other agents. This polymer releases the drug in a controlled manner with no burst release. These systems have a potential use as drug carriers for regional or systemic drug delivery.     

Recent Advances in Metal-Based Magnetic Composites as High-Efficiency Candidates for Ultrasound-Assisted Effects in Cancer Therapy

Metal-based magnetic materials have been used in different fields due to their particular physical or chemical properties. The original magnetic properties can be influenced by the composition of constituent metals. As utilized in different application fields, such as imaging monitoring, thermal treatment, and combined integration in cancer therapies, fabricated metal-based magnetic materials can be doped with target metal elements in research. Furthermore, there is one possible new trend in human activities and basic cancer treatment. As has appeared in characterizations such as magnetic resonance, catalytic performance, thermal efficiency, etc., structural information about the real morphology, size distribution, and composition play important roles in its further applications. In cancer studies, metal-based magnetic materials are considered one appropriate material because of their ability to penetrate biological tissues, interact with cellular components, and induce noxious effects. The disruptions of cytoskeletons, membranes, and the generation of reactive oxygen species (ROS) further influence the efficiency of metal-based magnetic materials in related applications. While combining with cancer cells, these magnetic materials are not only applied in imaging monitoring focus areas but also could give the exact area information in the cure process while integrating ultrasound treatment. Here, we provide an overview of metal-based magnetic materials of various types and then their real applications in the magnetic resonance imaging (MRI) field and cancer cell treatments. We will demonstrate advancements in using ultrasound fields co-worked with MRI or ROS approaches. Besides iron oxides, there is a super-family of heterogeneous magnetic materials used as magnetic agents, imaging materials, catalytic candidates in cell signaling and tissue imaging, and the expression of cancer cells and their high sensitivity to chemical, thermal, and mechanical stimuli. On the other hand, the interactions between magnetic candidates and cancer tissues may be used in drug delivery systems. The materials’ surface structure characteristics are introduced as drug loading substrates as much as possible. We emphasize that further research is required to fully characterize the mechanisms of underlying ultrasounds induced together, and their appropriate relevance for materials toxicology and biomedical applications.     

Nanoparticles in Clinical Translation for Cancer Therapy

The advent of cancer therapeutics brought a paradigm shift from conventional therapy to precision medicine. The new therapeutic modalities accomplished through the properties of nanomaterials have extended their scope in cancer therapy beyond conventional drug delivery. Nanoparticles can be channeled in cancer therapy to encapsulate active pharmaceutical ingredients and deliver them to the tumor site in a more efficient manner. This review enumerates various types of nanoparticles that have entered clinical trials for cancer treatment. The obstacles in the journey of nanodrug from clinic to market are reviewed. Furthermore, the latest developments in using nanoparticles in cancer therapy are also highlighted.     

Exosomes: Isolation,Analysis, and Applications in Cancer Detection and Therapy

Exosomes are cell-derived small extracellular vesicles that are naturally secreted by all types of cells and widely distributed in various biofluids. They carry a variety of key bioactive molecules (e.g., nucleic acids, proteins, growth factors, cytokines) from their parent cells and convey them to neighboring or even distant cells through circulation. In recent years, tumor-derived exosomes have attracted great interest from investigators because they actively participate in nearly all aspects of tumor development and facilitate both tumor growth and metastasis through exosome-mediated intercellular communication. The vesicular contents are increasingly considered potential biomarkers for tumor diagnoses and prognosis. With the progress made in isolation and analytical technologies, the functions of exosomes and their contents in tumor development are also becoming clearer. In this review article we describe the recent developments in exosome isolation techniques and analysis of exosomal contents. We also address their applications in cancer detection and therapy.     

A Parametric Study of a Portable Magnetic Separator for Separation of Nanospheres from Circulatory System

A portable magnetic separator was proposed for in-vivo biomedical applications. In this prototype design, a matrix of alternating, parallel magnetizable wires, and biocompatible tubing is immersed into an externally applied magnetic field. The wires are magnetized and high magnetic fields as well as field gradients are created to trap blood-borne flowing magnetic nanospheres in the tube. In this paper, a parametric investigation was carried out to evaluate the capture efficiency of flowing magnetic nanospheres by a separator unit consisting of single tubing and four wires. The parameters include: mean blood velocity (1 to 20 cm/s); magnetic field strength (0.1 to 2.0 T); sphere size (500 nm to 1000 nm in radii); sphere magnetic material (iron, two types of magnetite) and magnetite content in the spheres (0.05 to 0.8 by weight); wire material (nickel, stainless steel 430, and Wairauite); wire length (2.0 to 20 cm); wire size (0.125 to 1.0 mm in radii); tubing size at a fixed ratio of tubing to wire diameter of unity. The results show that capture efficiencies of the spheres of well over 90% were achievable under reasonable human physiological conditions, provided that the mean blood velocities were below about 5.0 cm/s. The results also show that the magnetic separator performance could be improved by maximizing the applied magnetic field strength up to about 1.0 T and by reducing the size of the unit with tubing and wires of equal radii. The results help further optimize a prototype magnetic separator suitable for rapid sequestration of magnetic nanospheres from the human blood stream while accommodating necessary clinical boundary conditions.     

Biocompatible PEGylated Fe3O4 Nanoparticles as Photothermal Agents for Near-Infrared Light Modulated Cancer Therapy

In accordance with the World Cancer Report, cancer has become the leading cause of mortality worldwide, and various therapeutic strategies have been developed at the same time. In the present study, biocompatible magnetic nanoparticles were designed and synthesized as high-performance photothermal agents for near-infrared light mediated cancer therapy in vitro. Via a facile one-pot solvothermal method, well-defined PEGylated magnetic nanoparticles (PEG–Fe₃O₄) were prepared with cheap inhesion as a first step. Due to the successful coating of PEG molecules on the surface of PEG–Fe₃O₄, these nanoparticles exhibited excellent dispersibility and dissolvability in physiological condition. Cytotoxicity based on MTT assays indicated these nanoparticles revealed high biocompatibility and low toxicity towards both Hela cells and C6 cells. After near-infrared (NIR) laser irradiation, the viabilities of C6 cells were effectively suppressed when incubated with the NIR laser activated PEG–Fe₃O₄. In addition, detailed photothermal anti-cancer efficacy was evaluated via visual microscope images, demonstrating that our PEG–Fe₃O₄ were promising for photothermal therapy of cancer cells.     

Light-Triggered Covalent Coupling of Gold Nanoparticles for Photothermal Cancer Therapy

Manipulating the cross-coupling of gold nanoparticles (AuNPs) to maximize the photothermal effect is a promising strategy for cancer therapy. Here, by taking advantage of the well-known tetrazole/alkene photoclick chemistry, we have demonstrated for the first time that small AuNPs (23 nm) decorated with both 2,5-diphenyltetrazole and methacrylic acid on their surfaces can form covalently crosslinked aggregates upon laser irradiation (λ=405 nm). In vitro studies indicated that the light-triggered assembling shifted the surface plasmon resonance of AuNPs significantly to near-infrared (NIR) regions, which as a consequence effectively enhanced the efficacy of photothermal therapy for 4T1 breast cancer cells. We thus believe that this new light-triggered cross-coupling approach might offer a valuable tool for cancer treatment.     

Novel Tumor-Targeting Nanoparticles for Cancer Treatment—A Review

Being one of the leading causes of death and disability worldwide, cancer represents an ongoing interdisciplinary challenge for the scientific community. As currently used treatments may face limitations in terms of both efficiency and adverse effects, continuous research has been directed towards overcoming existing challenges and finding safer specific alternatives. In particular, increasing interest has been gathered around integrating nanotechnology in cancer management and subsequentially developing various tumor-targeting nanoparticles for cancer applications. In this respect, the present paper briefly describes the most used cancer treatments in clinical practice to set a reference framework for recent research findings, further focusing on the novel developments in the field. More specifically, this review elaborates on the top recent studies concerning various nanomaterials (i.e., carbon-based, metal-based, liposomes, cubosomes, lipid-based, polymer-based, micelles, virus-based, exosomes, and cell membrane-coated nanomaterials) that show promising potential in different cancer applications.     

A Bimetallic Nanozyme with Cascade Effect for Synergistic Therapy of Cancer

Novel nanocomposites were constructed through encapsulation of Au nanoparticles and Ru nanoparticles into dendritic mesoporous silica (DMSN-Au-Ru NPs). These exhibit improved effects due to a cascade catalytic ability for the synergistic therapy of cancer. Au nanoparticles with glucose oxidase-like properties were found to catalyze the oxidation of glucose to produce H₂O₂, while Ru nanoparticles could decompose H₂O₂ and produce toxic ¹O₂ for improved photodynamic therapy (PDT). In addition, the nanocomposites were found to have good photothermal performance under irradiation by near-infrared (NIR) light. Both in vitro and in vivo experiments show that the nanocomposites have good therapeutic effects due to the cascade catalytic effect and synergistic effect. These findings provide an effective way to design a new generation of nanodrugs for highly efficient cancer treatment.     

Nanomedicine-Based Delivery Strategies for Breast Cancer Treatment and Management

Breast cancer is one of the most common types of cancer among women globally. It is caused by mutations in the estrogen/progesterone receptors and conventional treatment methods are commonly utilized. About 70–80 percent of individuals with the early-stage non-metastatic disease may be cured. Conventional treatment is far less than the optimal ratio, as demonstrated through the high mortality rate of women with this cancer. However, conventional treatment methods like surgery, radiotherapy, and chemotherapy are not as effective as expected and lead to concerns about low bioavailability, low cellular uptake, emerging resistance, and adverse toxicities. A nanomedicine-based approach is a promising alternative for breast cancer treatment. The present era is witnessing rapid advancements in nanomedicine as a platform for investigating novel therapeutic applications and modern intelligent healthcare management strategies. This paper focuses on nanomedicine-based therapeutic interventions that are becoming more widely accepted for improving treatment effectiveness and reducing undesired side effects in breast cancer patients. By evaluating the state-of-the-art tools and taking the challenges involved into consideration, various aspects of the proposed nano-enabled therapeutic approaches have been discussed in this review.