Delivery System For Cancer Therapy Research Articles

Exosomes and Their Application as Drug Delivery System in Cancer Therapy

Exosomes are extracellular vesicles naturally released from cells. Exosomes from different sources play different roles in cellular component exchange, signal transduction, and pathological development. Exosomes have distinct biological characteristics such as low immunogenicity, easy uptake by cells, crossing the blood-brain barrier, natural targeting, and easy modification. Many studies show that exosomes as drug carriers have a great application prospect in cancer therapy. In this review, we review the biogenesis, origin, biological characteristics of exosomes, and the exosome drug delivery system and its application for cancer therapy are summarized to provide a reference for the study of exosomes.

Development of injectable upconversion nanoparticle-conjugated doxorubicin theranostics electrospun nanostructure for targeted photochemotherapy in breast cancer.

Nanotheranostic-based photochemotherapies with targeted drug delivery have considerably surfaced in cancer therapy. In the presented work, polyethyleneimine-coated upconversion nanoparticles were engineered to conjugate covalently with doxorubicin. Upconversion nanoparticles (UCNP)-Doxorubicin (DOX)/synthesized epidermal growth factor receptor-targeting peptide blended with polymer composite was electrospun and formulated as the injectable dosage form. The size of the UCNP and the nanofiber diameter were assessed as 26.75 ± 1.54 and 162 ± 2.82 nm, respectively. The optimized ratio of dopants resulted in UCNP photoluminescence with maximum emission intensity at around 800 nm upon 980 nm excitation wavelength. The paramagnetic nature of UCNPs and amide conjugation with the drug was confirmed analytically. The loading capacity of UCNP for doxorubicin was determined to be 54.56%, while nanofibers exhibited 98.74% capacity to encapsulate UCNP-DOX. The release profile of UCNP-DOX from nanofiber formulation ranged from sustained to controlled, with relative enhancement in acidic conditions. The nanofiber demonstrated good mechanical strength, robust swelling, and degradation rate. Biocompatibility tests showed more than 90% cell viability on L929 and NIH/3T3 cell lines with UCNP-DOX@NF/pep nanoformulation. The IC50 values of 2.15 ± 0.54, 2.87 ± 0.67, and 3.42 ± 0.45 μg/mL on MDA-MB-231, 4T1, and MCF-7 cancer cell line, respectively, with a significant cellular uptake, has been reported. The UCNP protruded a ≈62.7°C temperature rise within 5 min of 980 nm laser irradiation and a power density of 0.5 W cm-2. The nanoformulation induced reactive oxygen species of 65.67% ± 3.21% and apoptosis by arresting the cell cycle sub-G1 phase. The evaluation conveys the effectiveness of the developed injectable theranostic delivery system in cancer therapy.

PH/GSH-responsive diselenide-containing micelle via backbone ketoxime cross-links for efficient drug delivery and controlled release

Stimulus-responsive polymers are promising drug delivery systems for cancer therapy. However, low drug loading and drug leakage of polymeric carriers remain challenges. Here, a crosslinked diselenide-containing micelle was developed with pH/GSH dual responsiveness. Polyesters with multiple diselenide bonds and pendant ketone groups were synthesized by the ring-opening copolymerization of three cyclic monomers (diselenide-containing macrocyclic carbonate, 2-oxepane-1,5-dione, and 1,3-dioxan-2-one). The crosslinked polyester was obtained by the oxime click reaction of pendant ketone groups with hydroxylamine and then self-assembled into crosslinked micelle. This crosslinked micelle remained stable for 14 days, and responded to disassembly under the condition of pH = 5.0 and 10 mM glutathione (GSH). When the crosslinked micelle was loaded with the chemotherapeutic drug DOX, which possessed an active ketone group, the encapsulation efficiency of the crosslinked micelle increased to 91.36 %. The cumulative DOX release reached approximately 45 % under pH = 5.0 and 10 mM GSH. Importantly, the crosslinked diselenide-containing micelle could be taken up in MCF-7 breast cancer cells, responding to the tumor microenvironment and releasing encapsulated DOX. This crosslinked diselenide-containing micelle with pH/GSH dual responsiveness was proven to be a stable and efficient carrier with a promising application.

Microstructure of dendrimers functionalized with folic acid as studied by molecular dynamics simulations

Poly(amidoamine) dendrimers (PAMAM), due to their unique properties such as nanometric size and shape, monodispersity, and numerous modifiable surface groups, are promising nanocarriers in a wide range of biomedical applications. However, amine-terminated PAMAM dendrimers have been proven to be toxic at physiological pH, which limits their biomedical application. It has been approved that the binding of folic acid (FA) to dendrimer reduces nanocarrier toxicity. Also, it can selectively target cancer cells with folate receptors (FR-α) overexpression. In this study, we have explored the structural features of FA-functionalized PAMAM dendrimers using all-atom molecular dynamics (MD) simulations. To this end, third and fourth generations of PAMAM dendrimers were functionalized with FA, and MD simulations were performed for 100 ns at 310 K and 1 bar at neutral pH. We have examined the effect of FA functionalization on the molecular size, solvent accessible surface area, structural changes of amidoamine monomers, and the solvation of investigated dendrimers. Our results reveal that G4FA is the most suitable drug delivery system for cancer therapy among others.

Nanoplatform-Based In Vivo Gene Delivery Systems for Cancer Therapy.

Gene therapy uses modern molecular biology methods to repair disease-causing genes. As a burgeoning therapeutic, it has been widely applied for cancer therapy. Since 1989, there have been numerous clinical gene therapy cases worldwide. However, a few are successful. The main challenge of clinical gene therapy is the lack of efficient and safe vectors. Although viral vectors show high transfection efficiency, their application is still limited by immune rejection and packaging capacity. Therefore, the development of non-viral vectors is overwhelming. Nanoplatform-based non-viral vectors become a hotspot in gene therapy. The reasons are mainly as follows. 1) Non-viral vectors can be engineered to be uptaken by specific types of cells or tissues, providing effective targeting capability. 2) Non-viral vectors can protect goods that need to be delivered from degradation. 3) Nanoparticles can transport large-sized cargo such as CRISPR/Cas9 plasmids and nucleoprotein complexes. 4) Nanoparticles are highly biosafe, and they are not mutagenic in themselves compared to viral vectors. 5) Nanoparticles are easy to scale preparation, which is conducive to clinical conversion and application. Here, an overview of the categories of nanoplatform-based non-viral gene vectors, the limitations on their development, and their applications in cancer therapy.

Construction of Smart DNA-Based Drug Delivery Systems for Cancer Therapy.

Due to the disadvantages of poor targeting, slow action, and low effectiveness of current commonly used cancer treatments, including surgery, chemotherapy, and radiotherapy, researchers have turned to DNA as a biomaterial for constructing drug delivery nanocarriers. DNA is favored for its biocompatibility and programmability. In order to overcome the limitations associated with traditional drug delivery systems (DDSs), researchers have developed smart-responsive DNA DDSs that can control drug release in response to specific physical or chemical stimuli at targeted sites. In this review, a summary of multiple targeted ligand structures is provided, various shapes of stable DNA nanomaterials, and different stimuli-responsive drug release strategies in DNA DDSs. Specifically, targeted cell recognition, in vivo stable transport, and controlled drug release of smart DDSs are focused. Finally, the further development prospects and challenges of clinical application of DNA nanomaterials in the field of smart drug delivery are discussed. The objective of this review is to enhance researchers' comprehension regarding the potential application of DNA nanomaterials in precision drug delivery, with the aim of expediting the clinical implementation of intelligent DDSs.

Bacteria Mediated Drug Delivery System for Cancer Therapy

Kanser tedavisine yönelik terapötiklerin ve tedavi yaklaşımlarının geliştirilmesine rağmen hastalık dünya çapında önde gelen ölüm nedenlerinden biridir. Spesifite eksikliği, sitotoksisite ve çoklu ilaç direnci gibi sınırlamalar nedeniyle kemoterapi, radyasyon terapisi ve immünoterapi gibi kanser tedavileri ile henüz istenen düzeyde başarı elde edilememiştir. Bu nedenle yan etkilerin azaltılarak etkin bir tedavinin gerçekleştirilebilmesi için hedefe yönelik tedavilerin geliştirilmesi büyük önem taşımaktadır. Ancak kanser mikroçevresi, vaskülarizasyonu ve hipoksik bölgeleri ile hedeflendirme için birçok fizyolojik engele sahiptir. 1800’lü yıllardan günümüze kadar yapılan araştırmalar, bakterilerin bu fizyolojik engelleri aşarak kanser dokusuna seçici olduğunu göstermiştir. Bakterilerin doğal olarak tümör dokularını hedefleme ve dokuda birikme özelliklerine sahip olduğunun keşfedilmesiyle birlikte araştırmacılar, bakteri destekli ilaç taşıyıcı sistemler üzerine yoğunlaşmıştır. Bakterilerin hareketlilik, immün yanıt oluşturma ve kolay modifikasyon özelliğiyle konvansiyonel ilaç taşıyıcı sistemlerden daha üstün olduğu bildirilmiştir. Bu derlemede kanser tedavisine yönelik bakteri destekli ilaç taşıyıcı sistemler konusunda literatürde yer alan en güncel gelişmeler değerlendirilmiştir.

Niosomes: Composition, Formulation Techniques, and Recent Progress as Delivery Systems in Cancer Therapy.

Niosomes are vesicular nanocarriers, biodegradable, relatively non-toxic, stable, and inexpensive, that provide an alternative for lipid-solid carriers (e.g., liposomes). Niosomes may resolve issues related to the instability, fast degradation, bioavailability, and insolubility of different drugs or natural compounds. Niosomes can be very efficient potential systems for the specific delivery of anticancer, antioxidant, anti-inflammatory, antimicrobial, and antibacterial molecules. This review aims to present an overview of their composition, the most common formulation techniques, as well as of recent utilizations as delivery systems in cancer therapy.

Revisiting edible insects as sources of therapeutics and drug delivery systems for cancer therapy.

Cancer has been medicine's most formidable foe for long, and the rising incidence of the disease globally has made effective cancer therapy a significant challenge. Drug discovery is targeted at identifying efficacious compounds with minimal side effects and developments in nanotechnology and immunotherapy have shown promise in the fight against this complicated illness. Since ancient times, insects and insect-derived products have played a significant role in traditional medicine across several communities worldwide. The aim of this study was to inspect the traditional use of edible insects in various cultures and to explore their modern use in cancer therapy. Edible insects are sources of nutrients and a variety of beneficial substances with anticancer and immunomodulatory potential. Recently, insect derived bioactive-components have also been used as nanoparticles either in combination with chemotherapeutics or as a nano-cargo for the enhanced delivery of chemotherapeutic drugs due to their high biocompatibility, low bio-toxicity, and their antioxidant and anticancer effects. The crude extracts of different edible insects and their active components such as sericin, cecropin, solenopsin, melittin, antimicrobial peptides and fibroin produce anti-cancer and immunomodulatory effects by various mechanisms which have been discussed in this review.

Effective Strategies in Designing Chitosan-hyaluronic Acid Nanocarriers: From Synthesis to Drug Delivery Towards Chemotherapy.

The biomedical field faces an ongoing challenge in developing more effective anti-cancer medication due to the significant burden that cancer poses on human health. Extensive research has been conducted on the utilization of natural polysaccharides in nanomedicine owing to their properties of biocompatibility, biodegradability, non-immunogenicity, and non-toxicity. These characteristics make them a potent drug delivery system for cancer therapy. The chitosan hyaluronic acid nanoparticle (CSHANp) system, consisting of chitosan and hyaluronic acid nanoparticles, has exhibited considerable potential as a nanocarrier for various cancer drugs, rendering it one of the most auspicious systems presently accessible. The CSHANps demonstrate remarkable drug loading capacity, precise control over drug release, and exceptional selectivity towards cancer cells. These properties enhance the therapeutic effectiveness against cancerous cells. This article aims to provide a comprehensive analysis of CSHANp, focusing on its characteristics, production techniques, applications, and future prospects.

Fabrication of hyaluronic acid with graphene quantum dot as a dual drug delivery system for cancer therapy

With recent advancements in nanomedicine, there has been growing interest in developing drug delivery systems with multifunctional capabilities. In this study, we developed a novel dual drug delivery system by combining two drug carriers via positive and negative electrostatic interactions. First, we modified polyethyleneimine (PEI) with graphene quantum dots (GQDs) to create a positively charged particle (GPI) with high drug loading efficiency and good dispersibility. Second, we embedded the pyrenebutyric acid structure in hyaluronic acid (HA) through EDC/NHS cross-linking and used TAK-632 as the hydrophobic drug to create negatively charged particles (HANPs) with hydrogel-like properties and the CD44 receptor. After the two components were constructed, the increase in the particle charge and simultaneous delivery of both drugs synergistically enhanced the therapeutic effect of this strategy. Qualitative tests confirmed the successful synthesis of the drug carrier, while the potential of this system as a cancer treatment strategy was evaluated in HCT116 cancer cells (through MTT cell viability assays) and in vivo mice xenograft experiments. Our results demonstrated that the dual drug delivery system, HANPs(TAK)/GPI(DOX), had a significant inhibitory effect on the growth of cancer cells both in vitro and in vivo, suggesting that this system is a promising candidate for a new type of treatment.

Recent Development and Future Aspects: Nano-Based Drug Delivery System in Cancer Therapy

Recent Development and Future Aspects: Nano-Based Drug Delivery System in Cancer Therapy

CRISPR/Cas gene editing and delivery systems for cancer therapy

AbstractCRISPR/Cas systems stand out because of simplicity, efficiency, and other superiorities, thus becoming attractive and brilliant gene‐editing tools in biomedical field including cancer therapy. CRISPR/Cas systems bring promises for cancer therapy through manipulating and engineering on tumor cells or immune cells. However, there have been concerns about how to overcome the numerous physiological barriers and deliver CRISPR components to target cells efficiently and accurately. In this review, we introduced the mechanisms of CRISPR/Cas systems, summarized the current delivery strategies of CRISPR/Cas systems by physical methods, viral vectors, and nonviral vectors, and presented the current application of CRISPR/Cas systems in cancer clinical treatment. Furthermore, we discussed prospects related to delivery approaches of CRISPR/Cas systems.This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

Advances in Ferroptosis-Inducing Agents by Targeted Delivery System in Cancer Therapy.

Currently, cancer remains one of the most significant threats to human health. Treatment of most cancers remains challenging, despite the implementation of diverse therapies in clinical practice. In recent years, research on the mechanism of ferroptosis has presented novel perspectives for cancer treatment. Ferroptosis is a regulated cell death process caused by lipid peroxidation of membrane unsaturated fatty acids catalyzed by iron ions. The rapid development of bio-nanotechnology has generated considerable interest in exploiting iron-induced cell death as a new therapeutic target against cancer. This article provides a comprehensive overview of recent advancements at the intersection of iron-induced cell death and bionanotechnology. In this respect, the mechanism of iron-induced cell death and its relation to cancer are summarized. Furthermore, the feasibility of a nano-drug delivery system based on iron-induced cell death for cancer treatment is introduced and analyzed. Secondly, strategies for inducing iron-induced cell death using nanodrug delivery technology are discussed, including promoting Fenton reactions, inhibiting glutathione peroxidase 4, reducing low glutathione levels, and inhibiting system Xc-. Additionally, the article explores the potential of combined treatment strategies involving iron-induced cell death and bionanotechnology. Finally, the application prospects and challenges of iron-induced nanoagents for cancer treatment are discussed.

Aptamer-Modified Tetrahedral DNA Nanostructures as Drug Delivery System for Cancer Targeted Therapy.

Improving the selective delivery and uptake efficiency of chemotherapeutic drugs remains a challenge for cancer-targeted therapy. In this work, a DNA tetrahedron is constructed as a targeted drug delivery system for efficient delivery of doxorubicin (Dox) into cancer cells. The DNA tetrahedron is composed of a tetrahedral DNA nanostructure (TDN) with two strands of AS1411 aptamer as recognition elements which can target the nucleolin protein on the cell membrane of cancer cells. The prepared DNA tetrahedron has a high drug-loading capacity and demonstrates pH-responsive Dox release properties. This enables efficient delivery of Dox into targeted cancer cells while reducing side effects on nontarget cells. The proposed drug delivery system exhibits significant therapeutic efficacy in vitro compared to free Dox. Accordingly, this work provides a good paradigm for developing a targeted drug delivery system for cancer therapy based on DNA tetrahedrons.

Novel carboxymethyl cellulose/polyvinyl pyrrolidone hydrogel incorporating graphitic carbon nitride for quercetin delivery

Herein, quercetin (QC) as a model anticancer drug was encapsulated in a carboxymethyl cellulose/polyvinyl pyrrolidone/graphitic carbon nitride (g-C3N4) nanocomposite synthesized via dual oil-in-water emulsification method. The nanocomposite hydrogel showed a high surface area, nano-porous structure and a hydroxylated surface. g-C3N4 enhanced the drug loading efficiency up to 95 %. X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR) analyses provided information about the crystalline structure of the nanocarrier and the interactions between its components, respectively. Field-emission scanning electron microscopy (FESEM) showed its spherical shape, with a mean particle size of 160 nm. Dynamic light scattering (DLS) revealed a monomodal and narrow particle distribution, with a PDI value of 0.12. Further, the average zeta potential was −38.7 mV, indicative of its high colloidal stability. The release kinetics of the drug-loaded nanocomposite was investigated at pH = 5.4 and 7.4, and the results showed a controlled and pH-sensitive release, with 97 % and 54 % QC released after 96 h, respectively. The mechanism of drug release was investigated via fitting the experimental release data to different kinetic models, and the best fitting were obtained for Korsmeyer–Peppas and Baker at pH 7.4 and 5.4, respectively. Significant cytotoxicity of the Qc-loaded nanocomposite on breast cancer model cells, MCF-7, was corroborated by flow cytometry and MTT assays. In addition, improved apoptotic cell death was attained due to the presence of g-C3N4 nanoparticles. Results support the high potential of the developed nanocomposite as a novel pH-responsive drug delivery system for cancer therapy.

Cell Membrane Biomimetic Nano-Delivery Systems for Cancer Therapy.

Nano-delivery systems have demonstrated great promise in the therapy of cancer. However, the therapeutic efficacy of conventional nanomedicines is hindered by the clearance of the blood circulation system and the physiological barriers surrounding the tumor. Inspired by the unique capabilities of cells within the body, such as immune evasion, prolonged circulation, and tumor-targeting, there has been a growing interest in developing cell membrane biomimetic nanomedicine delivery systems. Cell membrane modification on nanoparticle surfaces can prolong circulation time, activate tumor-targeting, and ultimately improve the efficacy of cancer treatment. It shows excellent development potential. This review will focus on the advancements in various cell membrane nano-drug delivery systems for cancer therapy and the obstacles encountered during clinical implementation. It is hoped that such discussions will inspire the development of cell membrane biomimetic nanomedical systems.

An analysis of the application prospects of nano-targeted drug delivery systems in cancer therapy

Cancer is an important cause of human death in the world today. Traditional cancer treatment methods have many defects, such as high damage to normal cells and the inability to efficiently remove tumor cells. In recent years, due to the EPR effect of nano-targeted drugs can stay in the tumor site for a long time, as well as their high specificity to cancer cells and better therapeutic ability than traditional drugs, more and more scholars believe that nano-targeted drug delivery system is a very promising research direction for cancer treatment. This article focuses on recent research in this field, focuses on targeting the tumor itself and various pathways by which T cells kill tumor cells, including promoting apoptosis, reversing polarization TAMs, Inducing iron death in cancer cells, Remodeling the tumor microenvironment and reprogramming metabolism. Through analysis of recent research, it was found that these methods have their own advantages and can be combined to improve the therapeutic effect of drugs. However, the more basic mechanism is still a blank, and more exploration is needed.

Folic acid-coupled bovine serum albumin-modified magnetic nanocomposites from quantum-sized Fe3O4 and layered double hydroxide for actively targeted delivery of 5-fluorouracil

The development of multifunctional magnetic nanocomposites as a drug delivery system for cancer therapy is highly desirable in current nanomedicine. Herein, folic acid-bovine serum albumin conjugate (FA-BSA) was modified on nanocomposites by combining quantum-sized Fe3O4 and layered double hydroxide (LDH) to obtain a novel FA-BSA/Fe3O4@LDH for the delivery of the anticancer drug 5-Fluorouracil (5-Fu). The prepared nanocomposites showed good dispersibility, colloidal stability, magnetic property and erythrocyte compatibility. FA-BSA/Fe3O4@LDH/5-Fu showed pH responsiveness, with both the amount and duration of release of FA-BSA/Fe3O4@LDH/5-Fu being significantly higher in pH 5.0 release medium than in pH 7.4 release medium. The cellular experiments implied that no significant cytotoxicity of FA-BSA/Fe3O4@LDH, particularly due to the presence of FA-BSA, which further enhanced the biocompatibility of the nanocomposite. Furthermore, FA-BSA/Fe3O4@LDH/5-Fu could specifically target the 2D HepG2 cells model and 3D hepatoma cell microspheres model in vitro, and efficient internalization through folate receptor-mediated endocytosis, showing excellent anti-cancer cell activity in a concentration-dependent manner. Therefore, the constructed FA-BSA/Fe3O4@LDH was able to provide a potential novel multifunctional nanocomposite for magnetic-targeting drug delivery and pH-responsive release of drugs to enhance the efficiency of cancer therapy.

An off-the-shelf small extracellular vesicle nanomedicine for tumor targeting therapy

Small extracellular vesicles (sEVs) have shown excellent prospects as drug delivery systems for cancer therapy. However, the inherent non-targeting and short blood circulation characteristics severely restrict their practical applications as a delivery system. In addition, post-encapsulating drugs into sEVs also remains challenging. Here, we constructed an engineered cell line that secreted multifunctional sEVs (termed NBsEV204) with 7D12 (an anti-EGFR nanobody) and hCD47 decorations on their surface, as well as high levels of miR-204-5p encapsulation. NBsEV204 exhibited extended blood circulation and improved macrophage-mediated phagocytosis of tumor cells by blocking CD47 signaling. Importantly, NBsEV204 specifically targeted EGFR+ tumor cells and showed robust tumor-suppressive effects both in vitro and in vivo. Overall, this study provides a convenient and feasible method to produce off-the-shelf anticancer sEV nanomedicine, which exhibits tremendous potential for clinical translation.