Targeted Drug Carriers Research Articles

Folate receptor-targeted thiol-maleimide clicked chitosan/carboxymethyl cellulose nanoparticles for cisplatin delivery in oral carcinoma.

This study aimed to develop cisplatin (CDDP)-loaded folic acid (FA)-decorated nanoparticles (NPs) as targeted drug carrier towards overexpressed folate receptors on the oral carcinoma cell line (KB cells). The FA-conjugated thiolated succinyl chitosan (FA-SH-SCS) and maleimide-grafted-carboxymethyl cellulose (CMC-MAL) were synthesized and acquired in the preparation of NPs via thiol-maleimide click reaction. The physicochemical characteristics, drug loading, and drug release of the FA-decorated NPs (FA-NPs) were examined. Also, the in vitro biocompatibility, cellular uptake, and cell death mechanism were investigated. Relatively spherical NPs with negative charge were obtained with a size of approximately 200 nm. The formation of FA-NPs through click reaction was confirmed by the pH change and Ellman's assay. The release of CDDP from the FA-NPs was influenced by the acidic tumor environment condition. The FA-NPs were non-toxic to the normal cells. Furthermore, FA-NPs improved the cellular uptake of CDDP in oral carcinoma cells through specific recognition of folate receptors by FA-NPs. The delivery of CDDP by FA-NPs to the KB cell induced the apoptotic cell death pathway. Therefore, FA-NPs presented the potential to be effective nanocarriers for CDDP delivery in the treatment of oral cancer via active targeting approach.

A review on exploring the potential of PVA and chitosan in biomedical applications: A focus on tissue engineering, drug delivery and biomedical sensors.

Polymers have been integral to the advancement of biomedicine, owing to their exceptional versatility and functionality. Among these, polyvinyl alcohol (PVA) and chitosan both natural polymers stand out for their remarkable biocompatibility, biodegradability, and unique properties. This review article provides a comprehensive examination of the diverse applications of PVA and chitosan in three pivotal areas: tissue engineering, drug delivery, and biosensors. In tissue engineering, the discussion centres on how PVA and chitosan are engineered into scaffolds that not only support cell growth and differentiation but also promote tissue regeneration by closely mimicking the extracellular matrix. These scaffolds offer the necessary mechanical strength and adaptability for various biomedical applications. For drug delivery, the article delves into the development of sophisticated controlled release systems and targeted drug carriers, highlighting the polymers' customizable properties and their mucoadhesive nature, which make them highly effective across multiple drug delivery methods. Furthermore, the potential of PVA and chitosan in biosensor technology is explored, particularly their ability to interact with biomolecules and their intrinsic conductivity attributes that are essential for creating sensitive, reliable, and biocompatible sensors for medical diagnostics. By synthesizing recent research findings and suggesting future research directions, this review underscores the versatility and critical role of PVA and chitosan in pushing the boundaries of biomedical innovation. It offers valuable insights for researchers and scientists dedicated to advancing healthcare through the application of these natural polymers.

Exosome applications for the diagnosis and treatment of pancreatic ductal adenocarcinoma: An update (Review).

Pancreatic ductal adenocarcinoma (PDAC) is a malignant neoplasm that typically manifests with subtle clinical manifestations in its early stages and frequently eludes diagnosis until the advanced phases of the disease. The limited therapeutic options available for PDAC significantly contribute to its high mortality rate, highlighting the urgent need for novel biomarkers capable of effectively identifying early clinical manifestations and facilitating precise diagnosis. The pivotal role of cellular exosomes in both the pathogenesis and therapeutic interventions for PDAC has been underscored. Furthermore, researchers have acknowledged the potential of exosomes as targeted drug carriers against regulatory cells in treating PDAC. The present article aims to provide a comprehensive review encompassing recent advancements in utilizing exosomes for elucidating mechanisms underlying disease development, patterns of metastasis, diagnostic techniques and treatment strategies associated with PDAC.

Macrophage corpses for immunoregulation and targeted drug delivery in treatment of collagen-induced arthritis mice

The role of pro-inflammatory macrophages (M1) in rheumatoid arthritis (RA) is significant, as they produce excessive cytokines. Targeting efferocytosis is a potential manner to repolarize M1 macrophages into pro-resolving M2 phenotype, which restores immune homeostasis by releasing anti-inflammatory mediators. In this study, liquid nitrogen-treated dead macrophages (DM) are employed to act as a dead cell-derived active targeted drug carrier for shikonin (SHK) and induce efferocytosis in M1 macrophages with the enhancement of SHK as an AMP-activated protein kinase (AMPK)-activator. The synergistic activation of AMPK leads to uncoupled protein 2 (UCP2) upregulation and reprograms M1 macrophages into M2 phenotypes by promoting oxidative phosphorylation. In the mouse model of collagen-induced arthritis, the intravenous administration of DM/SHK leads to a consistent transformation of M1 macrophages into the M2 phenotype within the infiltrative synovium. This transformation of macrophages results in the restoration of immune homeostasis in the synovium through an increase in the production of pro-resolving mediators. Additionally, it inhibits synovial proliferation and infiltration and provides protection against erosion of cartilage and bone. In summary, LNT-based DM serves as an active targeting drug carrier to M1 macrophages and also acts synergistically with SHK to target immunometabolism.

The Importance of Biotinylation for the Suitability of Cationic and Neutral Fourth-Generation Polyamidoamine Dendrimers as Targeted Drug Carriers in the Therapy of Glioma and Liver Cancer.

In this study, we hypothesized that biotinylated and/or glycidol-flanked fourth-generation polyamidoamine (PAMAM G4) dendrimers could be a tool for efficient drug transport into glioma and liver cancer cells. For this purpose, native PAMAM (G4) dendrimers, biotinylated (G4B), glycidylated (G4gl), and biotinylated and glycidylated (G4Bgl), were synthesized, and their cytotoxicity, uptake, and accumulation in vitro and in vivo were studied in relation to the transport mediated by the sodium-dependent multivitamin transporter (SMVT). The studies showed that the human temozolomide-resistant glioma cell line (U-118 MG) and hepatocellular carcinoma cell line (HepG2) indicated a higher amount of SMVT than human HaCaT keratinocytes (HaCaTs) used as a model of normal cells. The G4gl and G4Bgl dendrimers were highly biocompatible in vitro (they did not affect proliferation and mitochondrial activity) against HaCaT and U-118 MG glioma cells and in vivo (against Caenorhabditis elegans and Wistar rats). The studied compounds penetrated efficiently into all studied cell lines, but inconsistently with the uptake pattern observed for biotin and disproportionately for the level of SMVT. G4Bgl was taken up and accumulated after 48 h to the highest degree in glioma U-118 MG cells, where it was distributed in the whole cell area, including the nuclei. It did not induce resistance symptoms in glioma cells, unlike HepG2 cells. Based on studies on Wistar rats, there are indications that it can also penetrate the blood-brain barrier and act in the central nervous system area. Therefore, it might be a promising candidate for a carrier of therapeutic agents in glioma therapy. In turn, visualization with a confocal microscope showed that biotinylated G4B penetrated efficiently into the body of C. elegans, and it may be a useful vehicle for drugs used in anthelmintic therapy.

Advancing Tumor-Targeted Chemo-Immunotherapy: Development of the CAR-M-derived Exosome-Drug Conjugate.

Traditional antibody-drug conjugates (ADCs) mainly suppress tumor growth through either chemotherapy with cytotoxic payloads or immunotherapy with immuno-modulators. However, a single therapeutic modality may limit their exploration. Herein, we developed a new type of drug conjugate termed CAR-EDC (CAR-M-derived exosome-drug conjugate) by using CAR-exosomes from CAR-M cells as the targeting drug carrier that contains a high level of CXCL10. CAR-exosomes could significantly enhance the immunological activation and migratory capacity of T lymphocytes and promote their differentiation into CD8+ T cells. It also increased the proportion of M1 macrophages. The CAR-EDC, covalently loaded with SN-38, was internalized into Raji cells through endocytosis mediated by the CAR molecules. It exerted excellent antitumor activity in vivo by virtue of not only chemotherapy by SN38 but also immunotherapy by CXCL10-mediated antitumor immunity. Generally, this study provides an exosome-drug conjugate system with enhanced antitumor effects over traditional ADCs through the synergism of chemotherapy and immunotherapy.

Enhanced curcumin solubility in epichlorohydrin engineered β-Cyclodextrin copolymer for gastric maladies

The present work relates to a β-cyclodextrin based drug delivery system with epichlorohydrin as cross-linking agent, with higher binding efficiency of the drug curcumin and enhanced solubility of the curcumin in complex form when simulated in gastric fluid and increased sustained release of curcumin from complex for 2 h to act in gastric region. Although cross-linking with epichlorohydrin (EPC) is a process studied long time ago, however its use as a gastric solubility enhancer for curcumin has been studied for the first time. The synthesized polymer was well characterized by FT-IR, SEM, XRD, TGA and particle size analysis. The polymer enhanced the water solubility of curcumin by ∼ 800–850 times and the gastric solubility was increased by ∼ 1400–1500 times and acted as a sustained release system as verified by the pepsin inhibition studies which makes it a potential drug carrier for gastric specific drug targeting that can be a promising treatment for gastritis and gastric ulcers.

Review on Study of Nanoparticles in Brain Targeting for Treatment Of Alzheimer’s

Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder, in which there is a progressive deterioration of intellectual and social functions, memory loss, personality changes and inability for self-care, and has become the fourth leading cause of death in developed countries. Pathogenesis of AD, there is a progressive deposition of β-amyloid (Aβ)- peptide in the hippocampal and cerebral cortical regions. This deposition is associated with the presence of neurofibrillary tangles (NFTs) and senile plaques. The senile plaques deposited between the neurons consist mainly protein β amyloid. Neurofibrillary tangles deposited inside the neurons fabricated from Tau protein. Diagnosing Alzheimer's requires careful medical evaluation thorough medical history, mental status testing, physical and neurological examination tests (such as blood tests and brain imaging), two classes of medications approved to treat AD. Cholinesterase inhibitors: Donepezil, Rivastigmine, Galantamine, NMDA receptor antagonists: Memantine. The major goal in designing nanoparticles as a delivery system are to control particle size, surface property and release of pharmacologically active agents in order to achieve the site-specific action of the drug at the therapeutic optimum rate and dose regimen of the agent to the CNS, but also the ability of the agent to access the relevant target site within the CNS. Many strategies have been developed to deliver the drug into brain by crossing the BBB: chemical delivery systems, magnetic drug targeting or drug carrier systems such as antibodies, liposomes or nanoparticles. Among those, nanoparticles have got a great concentration as the potential targeted drug delivery systems in the brain recently. Keywords: Alzheimer’s disease, β-amyloid, cholinesterase inhibitors, Curcumin nanoparticles.

Effective therapy of advanced breast cancer through synergistic anticancer by paclitaxel and P-glycoprotein inhibitor

Multi-drug resistance (MDR) in advanced breast cancer (ABC) is triggered by the high expression of P-glycoprotein (P-gp), which reduces intracellular concentration of anti-tumor drugs, in turn preventing oxidative stress damage to cytoplasmic and mitochondrial membranes. It is therefore of clinical relevance to develop P-gp-specific targeted nanocarriers for the treatment of drug resistant ABC. Herein, a drug carrier targeting CD44 and mitochondria was synthesised for the delivery of encequidar (ER, P-gp inhibitor) and paclitaxel (PTX). HT@ER/PTX nanoparticles (ER:PTX molar ratio 1:1) had excellent P-gp inhibition ability and targeted mitochondria to induce apoptosis in MCF-7/PTX cells in vitro. Furthermore, HT@ER/PTX nanocarriers showed more anti-tumor efficacy than PTX (Taxol®) in a xenograft mouse model of MCF-7/PTX cells; the tumor inhibitory rates of HT@ER/PTX nanoparticles and Taxol® were 72.64% ± 4.41% and 32.36% ± 4.09%, respectively. The survival of tumor-bearing mice administered HT@ER/PTX nanoparticles was prolonged compared to that of the mice treated with Taxol®. In addition, HT@ER/PTX not only inhibited P-gp-mediated removal of toxic lipid peroxidation byproducts resulting from anti-tumor drugs but also upregulated the expression of mitochondrial dynamics-related protein, fostering oxidative stress damage, which induced activation of the Caspase-3 apoptosis pathway. Our findings indicate that mitochondria targeted co-delivery of anti-tumor drugs and P-gp inhibitors could be a practical approach in treating multi-drug resistance in ABC.

The application of nanomaterials in tumor therapy based on the regulation of mechanical properties.

Mechanical properties, as crucial physical properties, have a significant impact on the occurrence, development, and metastasis of tumors. Regulating the mechanical properties of tumors to enhance their sensitivity to radiotherapy and chemotherapy has become an important strategy in the field of cancer treatment. Over the past few decades, nanomaterials have made remarkable progress in cancer therapy, either based on their intrinsic properties or as drug delivery carriers. However, the investigation of nanomaterials of mechanical regulation in tumor therapy is currently in its initial stages. The mechanical properties of nanomaterials themselves, drug carrier targeting, and regulation of the mechanical environment of tumor tissue have far-reaching effects on the efficient uptake of drugs and clinical tumor treatment. Therefore, this review aims to comprehensively summarize the applications and research progress of nanomaterials in tumor therapy based on the regulation of mechanical properties, in order to provide strong support for further research and the development of treatment strategies in this field.

Chiral self-assembled (β,d)-RIB-TPE micron vesicles with AIE characteristics used as targeting-drug carriers

The synthetic material (β,d)-RIB-TPE, which can realize the specific recognition of the drug S-(+)-clopidogrel sulfate. The drug S-(+)-clopidogrel sulfate could be embedded, and the embedding rate was 45.7%.

Atorvastatin-based nanoparticle-decorated glyceryl monostearate as a targeted drug carrier for inhibition of atherosclerosis lesions

Macrophages play a significant role in various phases of a chronic atherosclerotic plaque of the arterial wall.

Platelets as delivery vehicles for targeted enrichment of NO· to cerebral glioma for magnetic resonance imaging

Using a magnetic resonance imaging (MRI) contrast agent, MRI has made substantial contributions to glioma diagnosis. Metal-free MRI agents, such as the nano free radical nitric oxide (NO·) micelle, can overcome the inherent toxicity of metal-based agents in certain patient populations. However, the low spatial resolution of nano NO· micelle in MRI limits its clinical development. In this study, we pretreated platelets (PLTs) and loaded them with nano NO· micelles to synthesize NO·@PLT, which can overcome the low contrast and poor in vivo stability of nitroxide-based MRI contrast agents. The PLTs can serve as potential drug carriers for targeting and delivering nano NO· micelles to gliomas and thus increase the contrast in T1-weighted imaging (T1WI) of MRI. This drug carrier system uses the unique tumor-targeting ability of PLTs and takes advantage of the high signal presentation of steady nano NO· micelles in T1WI, thereby ultimately achieving signal amplification of glioma in T1WI. With the effect of PLTs-tumor cell adhesion, NO·@PLT has per-nitroxide transverse relativities of approximately 2-fold greater than those of free NO· particles. These features allow a sufficient NO·@PLT concentration to accumulate in murine subcutaneous glioma tumors up from 5 min to 2.5 h (optimum at 1.5 h) after systemic administration. This results in MRI contrast comparable to that of metal-based agents. This study established a promising metal-free MRI contrast agent, NO·@PLT, for glioma diagnosis, because it has superior spatial resolution owing to its high glioma-targeting ability and has significant translational implications in the clinic.

A versatile strategy to construct surface functionalized pH/redox dual stimuli‐responsive nanogels for targeted drug delivery

AbstractDeveloping facile, green, and efficient synthetic methodology for preparing surface‐functionalized nanogels has attracted tremendous attention in the field of polymer chemistry and biomaterials engineering. Herein, a series of “clickable” P(MAA‐PMA) nanogels with reactive alkyne groups were conveniently prepared by “one‐pot” reflux‐precipitation polymerization (RPP), their particle sizes and zeta potentials are solid content‐dependent. Using P(MAA‐PMA)‐1 nanogels as the model, the physicochemical properties including particle size, surface potential, morphology, solution stability, and pH/redox responsiveness were characterized in detail. Moreover, the pH/redox dual‐responsive drug release feature/kinetics and parameters were analyzed using Korsmeyer–Peppas model and Gallagher–Corrigan model. Then the surface of nanogels was facilely modified with various thiol‐containing functional ligands via thiol‐yne photo click reaction. As targeted drug carriers, doxorubicin (DOX)‐loaded folic acid (FA)‐functionalized nanogels (FA@Nanogels/DOX) demonstrated higher tumor cell proliferation inhibition effect in B16F10 cancer cells than that in CHO‐K1 normal cells, while the non‐FA‐functionalized counterparts (Nanogels/DOX) do not show similar effect. This work provides a versatile “one‐pot RPP‐photo Click functionalization” strategy to construct surface‐functionalized pH/redox dual responsive nanogels for efficient and targeted drug delivery.

Gelatin microsphere-alginate hydrogel combined system for sustained and gastric targeted delivery of 5-fluorouracil

In the current study, novel gelatin microspheres/methacrylated alginate hydrogel combined system (5-FU-GELms/Alg-MA) was developed for gastric targeted delivery of 5-fluorouracil as an anticancer agent. While water-in-oil emulsification method was used for the production of 5-FU-GELms, Alg-MA was synthesized through methacrylation reaction occurred by epoxide ring-opening mechanism. Then, 5-FU-GELms/Alg-MA hydrogel system was fabricated by the encapsulation of 5-FU-GELms into Alg-MA hydrogel network via UV-crosslinking. To evaluate applicability of fabricated 5-FU-GELms/Alg-MA as gastric targeted drug delivery vehicle, both swelling and in vitro drug release experiments were carried out at pH 1.2 medium resembling gastric fluid. Compared to drug release directly from 5-FU-GELms, 5-FU-GELms/Alg-MA hydrogel system showed more controlled and sustained drug release profile with lower amount of cumulative release starting from early stages, since hydrogel matrix created a barrier to the diffusion of 5-FU included in microspheres. Drug release kinetic results obtained by applying various kinetic models to release data showed that the mechanism of 5-FU release from 5-FU-GELms/Alg-MA hydrogel system is controlled by Fickian diffusion. All results revealed that 5-FU-GELms/Alg-MA hydrogel integrated system could be potentially utilized as gastric targeted drug carrier to enhance therapeutic efficacy and reduce systemic side effects in gastric cancer treatments for future studies.

Potential applications of Folate-conjugated Chitosan Nanoparticles for Targeted delivery of Anticancer drugs

Folate-conjugated chitosan nanoparticles represent a promising nanoplatform for targeted delivery of anticancer drugs. The nanoparticle carrier can protect the therapeutic agents from degradation and offer the ability to target cancer cells overexpressing folate receptors. This review summarizes recent research progress in synthesizing folate-conjugated chitosan nanoparticles as well as evaluating their potential as targeted drug delivery systems. The chemical conjugation of folic acid to chitosan is first discussed followed by an overview of different techniques for preparation of stable folate-conjugated chitosan nanoparticles less than 200 nm in size. Recent studies loading various anticancer drugs into these nanoparticles and investigating their in vitro cytotoxicity against multiple cancer cell lines are then summarized. The results indicate that folate-conjugated nanoparticles exhibit higher cytotoxicity and targeting efficiency compared to non-conjugated nanoparticles due to receptor-mediated endocytosis. Lastly, future challenges and opportunities are outlined including in vivo investigations to determine the effectiveness, toxicity, and pharmacokinetics of folate-conjugated chitosan nanoparticle systems as well as their potential clinical translation as targeted drug carriers for cancer chemotherapy.

Role of Albumin as a Targeted Drug Carrier in the Management of Rheumatoid Arthritis: A Comprehensive Review.

An endogenous transporter protein called albumin interacts with the Fc receptor to provide it with multiple substrate-binding domains, cell membrane receptor activation, and an extended circulating half-life. Albumin has the remarkable ability to bind with receptors viz. secreted protein acidic and rich in cysteine (SPARC) and scavenger protein-A (SR-A) that are overexpressed during rheumatoid arthritis (RA), enabling active targeting of the disease site instead of requiring specialized substrates to be added to the nanocarrier. RA, a chronic autoimmune illness, is characterized by the presence of a severe inflammatory response. RA patients have low serum albumin concentration, which signifies the high uptake of albumin at the inflammatory sites, giving a rationale to use albumin as a drug carrier for RA therapy. Albumin has the capacity for both passive and active targeting. It is an abundantly available protein in the bloodstream showing excellent cellular compatibility, degradability in biological tissues, nonantigenicity, and safety. There are three strategies of albumin mediated drug delivery as encapsulating therapeutics in albumin nanoparticles, chemically conjugating drugs with functional proteins, and albumin itself which is used as a targeting ligand to deliver drugs specifically to cells or tissues that express albumin-binding receptors. In the current review, an attempt has been made to highlight the significant evidence of albumin as a drug delivery carrier for the safe and effective management of RA. Evidence has been provided in the form of recent research advances, clinical trials, and patents. Additionally, this review will outline the prospective for the potential utilization of albumin as a drug vehicle for RA and suggest possible future avenues to provide the perspective for subsequent studies.

Enhanced anti-cancer effects of magnetic targeted pH-sensitive curcumin delivery system based on heterogeneous magnetic α-Fe2O3/Fe3O4 nanoparticles on gastric cancer SGC-7901 cells

ProblemUnhealthy dietary habits and inadequate existing treatment technologies have led to high morbidity and mortality rates in patients with gastric cancer, and the research shows that curcumin has excellent antitumor properties, however, the non-water-soluble characteristic of curcumin limits its applications. To break the limitation, the targeted drug carriers become the urgent need to treat gastric cancer. MethodThe heterogeneous magnetic α-Fe2O3/Fe3O4 nanoparticles were obtained by rapid combustion method with citric acid (CA) and ferric nitrate as raw materials and anhydrous ethanol as solvent and fuel, and then modified with citric acid (CA) and chitosan (CTS), and loaded curcumin (Cur) to form α-Fe2O3/Fe3O4-CA-CTS-Cur nanosystem. ResultsThe particle sizes of heterogeneous magnetic α-Fe2O3/Fe3O4 nanoparticles and α-Fe2O3/Fe3O4-CA-CTS-Cur nanosystem were 24.9 nm and 35.6 nm, respectively, and their respective saturation magnetization were 70.9 emu/g and 30.3 emu/g. The magnetic α-Fe2O3/Fe3O4-CA-CTS-Cur nanosystem had good stability, excellent drug release rate, and enhanced apoptosis to gastric cancer cells (SGC-7901) through the caspase pathway and ferroptosis of cells. ConclusionsThe magnetic drug delivery nanosystem was successfully constructed, and revealed significant inhibitory and killing effects on SGC-7901 cells, and low toxic and side effects on normal cells.

Nanodrug Delivery Strategies to Signaling Pathways in Alopecia.

Over 50% of the global population suffers from hair loss. The mixed results in the treatment of hair loss reveal the limitations of conventional commercial topical drugs. One the one hand, the definite pathogenesis of hair loss is still an enigma. On the other hand, targeted drug carriers ensure the drug therapeutic effect and low side effects. This review highlights the organization and overview of nine crucial signaling pathways associated with hair loss, as well as the development of nanobased topical delivery systems loading the clinical drugs, which will fuel emerging hair loss treatment strategies.

Preparation and Characterization of Targeted Drug Carrier Materials Poly-β-Cyclodextrin-PEG-Folate Acid

Preparation and Characterization of Targeted Drug Carrier Materials Poly-β-Cyclodextrin-PEG-Folate Acid