Targeted Drug Delivery Systems Research Articles

Stem Cell-Nanodiamond Synergy: Efficacy in Breast Cancer

In the intricate and evolving landscape of oncological research and therapeutic modalities, the imperative for sophisticated, precise, and holistic strategies becomes paramount, especially within the intricate realm of breast cancer management. This analytical discourse undertakes a comprehensive examination of the synergistic interplay between stem cells and nanodiamonds, unveiling their collective potential to pioneer transformative therapeutic paradigms. Within the confines of this discussion, stem cells are acknowledged for their intrinsic adaptability and potent regenerative properties, whereas nanodiamonds are recognized for their versatile functions in targeted drug delivery systems and their inherent biocompatibility. Individually, they embody diverse therapeutic prospects; however, it is their collaborative interaction that is positioned at the vanguard of this evaluative discourse. The elaborate biophysical and biochemical exchanges incited by the amalgamation of stem cells’ regenerative prowess and nanodiamonds’ precision in drug conveyance are meticulously analyzed. This analysis transcends conventional scrutiny, delving into the profound molecular mechanisms, cellular kinetics, and resultant clinical ramifications, thereby delineating a comprehensive blueprint for an integrated therapeutic strategy.

Reactive oxygen species (ROS)-responsive biomaterials for treating myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury (MIRI) is a critical issue that arises when restoring blood flow after an ischemic event in the heart. Excessive reactive oxygen species (ROS) production during this process exacerbates cellular damage and impairs cardiac function. Recent therapeutic strategies have focused on leveraging the ROS microenvironment to design targeted drug delivery systems. ROS-responsive biomaterials have emerged as promising candidates, offering enhanced therapeutic efficacy with reduced systemic adverse effects. This review examines the mechanisms of ROS overproduction during myocardial ischemia-reperfusion and summarizes significant advancements in ROS-responsive biomaterials for MIRI treatment. We discuss various chemical strategies to impart ROS sensitivity to these materials, emphasizing ROS-induced solubility switches and degradation mechanisms. Additionally, we highlight various ROS-responsive therapeutic platforms, such as nanoparticles and hydrogels, and their unique advantages in drug delivery for MIRI. Preclinical studies demonstrating the efficacy of these materials in mitigating MIRI in animal models are reviewed, alongside their mechanisms of action and potential clinical implications. We also address the challenges and future prospects of translating these state of the art biomaterial-based therapeutics into clinical practice to improve MIRI management and cardiac outcomes. This review will provide valuable insights for researchers and clinicians working on novel therapeutic strategies for MIRI intervention.

Carbon Nanotubes an Excellent Targeted Drug Delivery System

Carbon nanotubes, or CNTs, are carbon allotropes with a nanostructure that can have a length-to-breadth proportion more prominent than 1,000,000. These round and hollow carbon particles have exceptional properties that make them possibly helpful in an assortment of nanotechnology applications. CNTs might be joined with a scope of natural components, including proteins, drugs, and nucleic acids, to give bio-functionalities. CNTs come in two assortments: multi-walled (MWNTs) and single-walled (SWNTs). Among its captivating properties are its high viewpoint proportion, strength, lightweight weight, high warm conductivity, and electrical attributes that reach from metallic to semiconducting. Carbon nanotubes might be made by various cycles, including warm blend, substance fume statement, laser removal, circular segment release dissipation, plasma-based union, and synthetic fume affidavit increased by plasma. Carbon nanotubes (CNTs) track down use in drug conveyance, blood malignant growth, bosom disease, cerebrum malignant growth, liver malignant growth, cervical malignant growth, quality treatment, resistant therapy, biomedical imaging, biosensors, and tissue designing. The noncovalent functionalization of specific MNTs with folic corrosive (FA) worked on the vehicle of medication to malignant growth cells in the lymph hubs. By utilizing a remotely introduced magnet to guide the medication lattice to the provincial designated lymph hubs, the MNTs can ceaselessly deliver chemotherapeutic medications for a few days while remaining in the depleting designated lymph hubs. Growth cells communicating folate receptors (FRs) in the lymph hubs can be explicitly obliterated since FRs are overexpressed in different human malignancies.

Advancing Ovarian Cancer Therapeutics: The Role of Targeted Drug Delivery Systems.

Ovarian cancer (OC) is the most lethal reproductive system cancer and a leading cause of cancer-related death. The high mortality rate and poor prognosis of OC are primarily due to its tendency for extensive abdominal metastasis, late diagnosis in advanced stages, an immunosuppressive tumor microenvironment, significant adverse reactions to first-line chemotherapy, and the development of chemoresistance. Current adjuvant chemotherapies face challenges such as poor targeting, low efficacy, and significant side effects. Targeted drug delivery systems (TDDSs) are designed to deliver drugs precisely to the tumor site to enhance efficacy and minimize side effects. This review highlights recent advancements in the use of TDDSs for OC therapies, including drug conjugate delivery systems, nanoparticle drug delivery systems, and hydrogel drug delivery systems. The focus is on employing TDDS to conduct direct, effective, and safer interventions in OC through methods such as targeted tumor recognition and controlled drug release, either independently or in combination. This review also discusses the prospects and challenges for further development of TDDSs. Undoubtedly, the use of TDDSs shows promise in the battle against OCs.

Unlocking the Potential of Drug Delivery Systems: A Comprehensive Review of Formulation Strategies and Technologies in the Field of Pharmaceutics

: The creation of innovative drug delivery systems to enhance therapeutic effectiveness, safety, and patient compliance has resulted in considerable developments in pharmaceutics in recent years. The most recent formulation techniques and technologies are reviewed in this article to improve medication distribution and accomplish specific therapeutic goals. : This article thoroughly summarizes the most recent formulation techniques and technologies used to enhance medication delivery and provide specific therapeutic effects. It discusses the variety of medication delivery methods, including nanoparticles, liposomes, micelles, and dendrimers, and explores the application of nanotechnology and biotechnology in drug delivery. Additionally, the paper emphasizes the significance of targeted drug delivery systems and their capacity to cross biological barriers including the blood-brain barrier and tumor microenvironment. : The review also addresses the challenges faced in developing and commercializing drug delivery systems and suggests potential solutions to overcome them. Furthermore, the article emphasizes the role of computational modeling and simulation in designing and optimizing drug delivery systems. : Overall, this review paper offers insightful information for pharmaceutics researchers, scientists, and practitioners that will help in the creation of novel drug delivery systems that improve patient outcomes and quality of life.

Chemo-Enzymatic Functionalization of Bovine Milk Exosomes with an EGFR Nanobody for Target-specific Drug Delivery.

Bovine milk exosomes (BmExo) have been identified as versatile nanovesicles for anti-cancer drugs delivery due to their natural availability and biocompatibility. However, tumor-specific delivery based on BmExo often requires post-isolation modifications of the membrane surface with active-targeting ligands. In this study, we report an alternative approach to functionalize BmExo with nanobody combining facile chemical modification and Sortase A-mediated site-specific ligation, as demonstrated by the development of an epidermal growth factor receptor (EGFR)-targeted drug delivery system. The BmExo membrane was first coated with a diglycine-containing amphiphile molecule, NH2-GG-PEG2000-DSPE, by hydrophobic insertion. The diglycine as nucleophiles displayed on the membrane enabled the subsequent ligation of the EGFR nanobody (7D12) by Sortase A (SrtA)-mediated site-specific transpeptidation. The successful construction of BmExo-7D12 was confirmed by Western blotting analysis, electron microscopy, and dynamic light scattering (DLS). As a demonstration model, BmExo-7D12 loaded with the chemotherapeutic drug doxorubicin (Dox) was shown to be able to deliver Dox to cancer cells in response to the expression of EGFR as manifested by immunocytochemistry and flow cytometry analysis. Finally, the cytotoxicity assay showed that BmExo-7D12-Dox was more effective in killing tumor cells with high EGFR expression while significantly reduced the non-specific toxicity to EGFR negative cells. In conclusion, these results demonstrate that 7D12-functionalized BmExo can serve as a target-specific delivery system for Dox to selectively kill EGFR-expressing tumor cells. This approach should prove to be versatile and efficient for the generation of protein-ligands modified BmExo.

Multi-Sensitive Au NCs/5-FU@Carr-LA Composite Hydrogels for Targeted Multimodal Anti-Tumor Therapy.

Multifunctional targeted drug delivery systems have been explored as a novel cancer treatment strategy to overcome limitations of traditional chemotherapy. The combination of photodynamic therapy and chemotherapy has been shown to enhance efficacy, but the phototoxicity of traditional photosensitizers is a challenge. In this study, we prepared a multi-sensitive composite hydrogel containing gold nanoclusters (Au NCs) and the temperature-sensitive antitumor drug 5-fluorourac il (5-FU) using carboxymethyl cellulose (Carr) as a dual-functional template. Au NCs were synthesized using sodium borohydride as a reducing agent and potassium as a promoter. The resulting Au NCs were embedded in the Carr hydrogel, which was then conjugated with lactobionic acid (LA) as a targeting ligand. The resulting Au NCs/5-FU@Carr-LA composite hydrogel was used for synergistic photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy. Au NCs/5-FU@Carr-LA releases the drug faster at pH 5.0 due to the acid sensitivity of the Carr polymer chain. In addition, at 50 °C, the release rate of Au NCs/5-FU@Carr-LA is 78.2%, indicating that the higher temperature generated by the photothermal effect is conducive to the degradation of Carr polymer chains. The Carr hydrogel stabilized the Au NCs and acted as a matrix for drug loading, and the LA ligand facilitated targeted delivery to tumor cells. The composite hydrogel exhibited excellent biocompatibility and synergistic antitumor efficacy, as demonstrated by in vitro and in vivo experiments. In addition, the hydrogel had thermal imaging capabilities, making it a promising multifunctional platform for targeted cancer therapy.

A versatile nanoplatform carrying cascade Pt nanozymes remodeling tumor microenvironment for amplified sonodynamic/chemo therapy of thyroid cancer

Thyroid cancer is increasing globally, with anaplastic thyroid carcinoma (ATC) being the most aggressive type and having a poor prognosis. Current clinical treatments for thyroid cancer present numerous challenges, including invasiveness and the necessity of lifelong medication. Furthermore, a significant portion of patients with ATC experience cancer recurrence and metastasis. To overcome this dilemma, we developed a pH-responsive biomimetic nanocarrier (CLP@HP-A) through the incorporation of Chlorin e6 (Ce6) and Lenvatinib (Len) within hollow polydopamine nanoparticles (HP) that were further modified with platinum nanoparticles (Pt), enabling synergistic chemotherapy and sonodynamic therapy. The CLP@HP-A nanocarriers exhibited specific binding with galectin-3 receptors, facilitating their internalization through receptor-mediated endocytosis for targeted drug delivery. Upon exposure to ultrasound (US) irradiation, Ce6 rapidly generated reactive oxygen species (ROS) to induce significant oxidative stress and trigger apoptosis in tumor cells. Additionally, Pt not only alleviated tumor hypoxia by catalyzing the conversion of H2O2 to oxygen (O2) but also augmented intracellular ROS levels through the production of hydroxyl radicals (•OH), thereby enhancing the efficacy of sonodynamic therapy. Moreover, Len demonstrated a potent cytotoxic effect on thyroid cancer cells through the induction of apoptosis. Transcriptomics analysis findings additionally corroborated that CLP@HP-A effectively triggered cancer cell apoptosis, thereby serving as a crucial mechanism for its cytotoxic effects. In conclusion, the integration of sonodynamic/chemo combination therapy with targeted drug delivery systems offers a novel approach to the management of malignant tumors.

Implementation of PLGA-based Nanoparticles for Treatment of Colorectal Cancer

: Colorectal cancer is more prevalent in females than males. There are many anticancer drugs accessible for use, but their therapeutic importance is constrained by factors including poor solubility, low absorption, and multi-drug resistance. This review highlights how PLGA may be used to develop polymeric- targeted drug delivery systems that specifically target colorectal cancer. The PLGA polymer, which is disseminated in the colon together with drugs in a regulated and targeted manner, has the distinct characteristics of smart degradation in a biological system. Its degradability is dependent on multiple glycolide units; therefore, a lower glycol concentration improves degradability and vice versa. Also, PLGA facilitates drug delivery in colorectal cancer, enhances the efficacy of the drug, improves the sustained release profile of a drug, improves bioavailability due to prolonged retention time in the colon, enhances solubility, etc. To develop the formulation for improving the cytotoxic impact of various anticancer drugs, the surface modification of PLGA can be carried out by introducing a copolymer. By emphasizing their crucial characterization to demonstrate their therapeutic potential, this literature work has also shed light on recent patents and advancements in PLGA application.

Enhancing targeted tumor treatment: A novel fuzzy logic framework for precision drug delivery strategy selection

Objective:This study aims to address the challenge of selecting optimal drug delivery strategies for tumor patients by introducing a novel theoretical framework. Methods:We propose a fuzzy logic-based framework for quantitatively assessing Health States (HS) in tumor patients. This framework integrates quantified HS assessments with causality strength analyses, offering a comprehensive understanding of various drug delivery schemes’ effectiveness from pharmacokinetic and pharmacodynamic perspectives. Results:The efficacy of our approach is demonstrated through a series of real-world patient case studies, highlighting its potential to enhance the evaluation and selection of targeted drug delivery strategies. Conclusion:Our work contributes to the field by showcasing practical applications of fuzzy logic in targeted drug delivery systems (TDDs) and establishing a new benchmark for precision in drug delivery strategy selection. Significance:This study has significant implications for developing personalized medical treatments, potentially revolutionizing the field with a more nuanced and scientifically rigorous method for evaluating and selecting drug delivery protocols. Contributions:Development of a fuzzy logic framework for precise quantification of health states in tumor patients. Innovative integration of a causal system for comprehensively evaluating targeted drug delivery strategies.

Redox-Responsive AIEgen Diselenide-Covalent Organic Framework Composites Targeting Hepatic Macrophages for Treatment of Drug-induced Liver Injury.

The escalating misuse of antipyretic and analgesic drugs, alongside the rising incidents of acute drug-induced liver injury, underscores the need for a precisely targeted drug delivery system. Herein, two isoreticular covalent organic frameworks (Se-COF and Se-BCOF) are developed by Schiff-base condensation of emissive tetraphenylethylene and diselenide-bridged monomers. Leveraging the specific affinity of macrophages for mannose, the first precise targeting of these COFs to liver macrophages is achieved. The correlation is also explored between the therapeutic effects of COFs and the NLRP3/ASC/Caspase-1 signaling pathway. Utilizing this innovative delivery vehicle, the synergistic delivery of matrine and berberine are accomplished, compounds extracted from traditional Chinese medicine. This approach not only demonstrated the synergistic effects of the drugs but also mitigated their toxicity. Notably, berberine, through phosphorylation of JNK and up-regulation of nuclear Nrf-2 and its downstream gene Mn-SOD expression, simultaneously countered excessive ROS and suppressed the activation of the NLRP3/ASC/Caspase-1 signaling pathway in injured liver tissues. This multifaceted approach proved highly effective in safeguarding against acute drug-induced liver injury, ultimately restoring liver health to normalcy. These findings present a novel and promising strategy for the treatment of acute drug-induced liver injury.

Preparation of double-loaded bitter ginseng derivative B21–DOX liposomes co-modified with SP94 and BR2 ligand and its in vitro anti-hepatocarcinogenic effect

Aim To construct a novel liposomal drug delivery system co-modified with SP94 and BR2 ligands, encapsulating both the bitter ginseng derivative B21 and doxorubicin (DOX), to achieve superior anti-tumour efficacy and reduced toxic side effects. Methods Liposomes were prepared using an organic phase reaction method, with B21 encapsulated in the lipid phase and DOX in the aqueous phase. The liposomes were further modified with SP94 and BR2 peptides. The characterisations, cytotoxicity, and in vitro targeting effects were assessed through various methods including ultraviolet spectrophotometry, high-performance liquid chromatography, nano-size analysis, ultrafiltration centrifugation, dialysis, transmission electron microscopy, flow cytometry, Methylthiazolyldiphenyl-tetrazolium bromide assay, confocal laser scanning microscopy, transwell assay, and tumorsphere assay. Results SP94/BR2-B21/DOX-LP liposomes were spherical with an average diameter of 120.87 ± 1.00 nm, a polydispersity index (PDI) of 0.223 ± 0.006, and a surface charge of −23.1 ± 1.27 mV. The encapsulation efficiencies for B21 and DOX were greater than 85% and 97% (mg/mg), respectively. The results indicated that SP94/BR2-B21/DOX-LP exhibited enhanced targeting and cytotoxicity compared to single-ligand modified and unmodified liposomes, with the combined encapsulation of B21 and DOX showing synergistic anti-hepatocarcinogenic effects. Conclusion SP94/BR2-B21/DOX-LP liposomes represent a promising targeted drug delivery system for hepatocellular carcinoma, offering improved membrane penetration, enhanced therapeutic efficacy, and reduced systemic toxicity.

Stimuli-Responsive Nanogel/Microgel Hybrids as Targeted Drug Delivery Systems: A Comprehensive Review

Stimuli-Responsive Nanogel/Microgel Hybrids as Targeted Drug Delivery Systems: A Comprehensive Review

Fast lipid vesicles and dielectric particles migration using thermal-gradient-induced forces

Abstract Lipid vesicles are small biological particles that can be used for both targeted drug delivery systems and clinical studies. Their optical manipulation, however, is limited by the small difference in refractive indices with the surrounding medium, as well as the requirement for high laser trapping powers. In this work, we combine gradient force and thermal forces to deliver and trap individual lipid vesicles with low-trapping laser powers. The total optothermal force exerted on liposomes causes them to migrate rapidly toward the laser focus with a high average migration velocity of 1.77 µm s−1 under 7.3% w/v polyethylene glycol (PEG) concentration and low trapping laser power of 1 mW. A high normalized experimental trap stiffness of 0.88 (pN µm) mW−1 was obtained at 7.3% w/v PEG/water solution. This work may open new ways for bioparticle sorting and manipulation with potential applications in cellular studies, drug delivery, biosensing, and medicine.

Cisplatin-induced pyroptosis: a double-edged sword in cancer treatment

Abstract Cancer is a major cause of death worldwide and a serious threat to human health. Cisplatin, a widely used first-line chemotherapeutic agent for various solid tumors, is renowned for its efficacy but is limited by significant cytotoxicity. Cisplatin triggers pyroptosis in tumor cells by activating Gasdermin proteins, thereby enhancing its anticancer efficacy. However, this same mechanism can induce pyroptosis in normal cells, causing inflammation and toxicity in healthy tissues, such as nephrotoxicity and ototoxicity. The objective of this review is to identify the major molecular targets for optimizing the cisplatin treatment window by summarizing recent advances in the pyroptosis caused by cisplatin in different cancer types and normal tissues. Among them, gasdermin D and gasdermin E are the main molecular targets involved in cisplatin-induced pyroptosis, and GSDMB also has similar effects. Future research directions include exploring targeted drug delivery systems and target regulating GSDMs (gasdermin protein family) to selectively modulate pyroptosis, thereby maximizing cisplatin’s anticancer effects while minimizing its side effects. Therefore, this review provides a comprehensive overview of cisplatin-induced pyroptosis, offering new insights into therapeutic strategies in cancer treatment.

Innovative Nanoscale Drug Delivery Strategies for Breast Carcinoma: A Comprehensive Exploration.

Breast cancer (BC) is one of the major causes of poor health in women and the most devastating disease after lung cancer. The term "cancer" refers to a collection of problems resulting from abnormal cell proliferation, particularly cells that can spread to other parts of the body. Surgery, followed by chemotherapy or radiotherapy, is now accepted for BC-related cancers. However, chemotherapy and radiotherapy are rarely effective in the treatment of BC due to the adverse effects of these treatments on healthy tissues and organs. Consequently, the use of NPs in targeted Drug Delivery Systems (DDSs) has emerged as a promising strategy for BC treatment. This review provides a summary of recent clinical investigations of nanoparticle-mediated DDS that offer a novel therapeutic strategy commonly used for the treatment of breast cancer.

Cancer cell-derived exosome based dual-targeted drug delivery system for non-small cell lung cancer therapy

Lung cancer is among most prevalent cancers in the world, in which non-small cell lung cancer (NSCLC) accounts for more than 85 % of all subtypes of lung cancers. NSCLC is often diagnosed at an advanced stage with a high mortality rate. Despite the demonstrated efficacy of chemotherapy in the treatment of NSCLC, the main drawback of current therapy is the lack of an effective drug-targeted delivery system, which may result in undesirable side effects during the clinical treatment. In this study, we construct a "dual-targeting" anti-cancer drug delivery platform by combining superparamagnetic iron oxide nanoparticles (SPIONs) with exosomes derived from NSCLC cells. We successfully promoted the targeted delivery of anti-drug doxorubicin (DOX) at the cellular levels by combining the homing targeted ability of exosomes with the magnetic targeted ability of SPIONs. Moreover, non-small cell lung cancer cell (NCI-h1299) tumor models were established. It was found that exosome-SPIONs (Exo-SPIONs) loaded with DOX exhibited optimal tumor tissue delivery and tumor suppression in the presence of an external magnetic field, and reduced the toxicity of the DOX to normal tissues. The constructed "dual-targeting" anti-cancer drug delivery platform holds promise for targeted chemotherapy for NSCLC.

A Comprehensive Review on the Nanotechnology-based Intranasal Drug Delivery Systems for Brain Targeting

A Comprehensive Review on the Nanotechnology-based Intranasal Drug Delivery Systems for Brain Targeting

Responsive-Hydrogel Aquabots.

It remains a challenge to produce soft robots that can mimic the responsive adaptability of living organisms. Rather than fabricating soft robots from bulk hydrogels,hydrogels are integrated into the interfacial assembly of aqueous two-phase systems to generate ultra-soft and elastic all-aqueous aquabots that exhibit responsive adaptability, that can shrink on demand and have electrically conductive functions. The adaptive functions of the aquabots provide a new platform to develop minimally invasive surgical devices, targeted drug delivery systems, and flexible electronic sensors and actuators.

Bacterial surface derived extracellular vesicles: A ground‐breaking approach in cancer therapy

AbstractConventional cancer therapies are often limited by inherent and acquired drug resistance, non‐specific toxicity, and suboptimal drug delivery. Bacterial extracellular vesicles (BEVs), including outer membrane vesicles and membrane vesicles, present a novel therapeutic strategy for cancer treatment. BEVs were found in both Gram‐negative and Gram‐positive bacteria. This article provides a classified investigation of the therapeutic potential of BEVs in cancer treatment. We discuss the molecular mechanisms underlying their observed anti‐tumor effects, including the induction of apoptosis in cancer cells, suppression of angiogenesis within the tumor microenvironment, and stimulation of both innate and adaptive anti‐tumor immune responses. Moreover, BEVs being biocompatible opens avenue for targeted drug delivery systems, potentially improving the therapeutic index of conventional chemotherapeutics. Challenges to clinical translation, such as BEV heterogeneity and potential immunogenicity, are addressed. We also explore future directions for research and development, comprehensively highlighting how BEVs transform the landscape of precision oncology and cancer treatment, eventually improving patient outcomes.