Intelligent Drug Delivery Systems Research Articles

A Biodegradable Nano-Drug Delivery Platform for Co-Delivery of Minocycline and Chitosan to Achieve Efficient and Safe Non-Surgical Periodontitis Therapy.

Mesoporous silica nanoparticles (MSN) are widely used as ideal nanovehicles for the delivery of chemotherapeutic drugs. However, the balance between high anti-periodontitis activity and low biotoxicity has been challenging to maintain in most relevant studies owing to the slow degradation of silica in living organisms. In this study, -responsive hydroxyapatite (HAP) was doped into the MSN skeleton, and the chemotherapeutic drug minocycline hydrochloride (MH) was loaded into the pores of MSN, forming a negatively charged drug delivery system. Cationic chitosan (COS) is a biodegradable material with high antibacterial performance and good biosafety. In this study, COS was immobilized on the surface of the drug-loaded particles through stable charge interaction to construct a composite drug delivery system (MH@MSNion@COS). In vitro and cellular experiments demonstrated effective degradation of the nanocarrier system and synchronized controlled release of the drug. Notably, compared with single MH administration, this system, in which MH and COS jointly regulated the expression levels of periodontitis- associated inflammatory factors (TNF-α, IL-6, IL-1β, and iNOS), better inhibited the progress of periodontitis and induced tissue regeneration without showing significant toxic side effects in cells. This system provides a promising strategy for the design of intelligent, efficient, and safe anti-periodontitis drug delivery systems.

Rational Design of Coordination Polymers Composited Hollow Multishelled Structures for Drug Delivery.

Multifunctional drug delivery systems (DDS) are in high demand for effectively targeting specific cells, necessitating excellent biocompatibility, precise release mechanisms, and sustained release capabilities. The hollow multishelled structure (HoMS) presents a promising solution, integrating structural and compositional design for efficient DDS development amidst complex cellular environments. Herein, starting from a Fe-based metal-organic framework (MOF), amorphous coordination polymers (CP) composited HoMS with controlled shell numbers are fabricated by balancing the rate of MOF decomposition and shell formation. Fe-CP HoMS loaded with DOX is utilized for synergistic chemotherapy and chemodynamic therapy, offering excellent responsive drug release capability (excellent pH-triggered drug release 82% within 72h at pH 5.0 solution with doxorubicin (DOX) loading capacity of 284mg g-1). In addition to its potent chemotherapy attributes, Fe-CP-HoMS possesses chemodynamic therapy potential by continuously catalyzing H2O2 to generate ·OH species within cancer cells, thus effectively inhibiting cancer cell proliferation. DOX@3S-Fe-CP-HoMS, at a concentration of 12.5µg mL-1, demonstrates significant inhibitory effects on cancer cells while maintaining minimal cytotoxicity toward normal cells. It is envisioned that CP-HoMS could serve as an effective and biocompatible platform for the advancement of intelligent drug delivery systems in the realm of cancer therapy.

Self-assembled nanoparticle-mediated cascade chemotherapy and chemodynamic therapy for enhanced tumor therapy

Chemodynamic therapy (CDT) is a non-invasive treatment strategy that aims to combat tumor growth by efficiently generating reactive oxygen species (ROS). However, the effectiveness of CDT can be limited by factors such as the availability of endogenous hydrogen peroxide (H2O2). Here, we established an intelligent nano-based drug delivery system responsive to the tumor microenvironment by self-assembling Cu2+, cisplatin, and L-histidine to form nanoparticles (Pt/CuH NPs), which can achieve the therapeutic effect of specific tumor killing by cascading chemotherapy with CDT. The Pt/CuH NPs are triggered by the acidic conditions and high glutathione (GSH) levels present in the tumor microenvironment, leading to the release of cisplatin and Cu2+. Cisplatin facilitates the production of H2O2 through a two-step enzymatic reaction, subsequently triggering ROS cascade that is amplified by CDT. Concurrently, Cu2+ consumes GSH and is reduced to Cu+, which reacts with H2O2 in an efficient Fenton-like reaction, amplifying oxidative stress and ultimately enhancing the anti-tumor therapeutic efficacy. Pt/CuH NPs demonstrated a significant cytotoxic effect on tumor cells in vitro. In vivo studies in mice indicated minimal toxic side effects at the tested dosages. The Pt/CuH NPs effectively combine chemotherapy and CDT strategies, showcasing the potential of a chemotherapy-cascading CDT approach for anti-tumor treatment.

Synthesis, characterization and evaluation of a pH-responsive molecular imprinted polymer for Matrine as an intelligent drug delivery system

Abstract To address the undesirable reactions associated with matrine (MAT) injection in clinical settings, a high-loading drug delivery system (DDS) based on pH-sensitive molecularly imprinted polymer (MAT@MIPs) was prepared for the first time. The imprinted materials containing recognition sites for the matrine were formed by using carboxyl-functionalized multiwalled carbon nanotubes as a supportive matrix and dopamine as a cross-linker due to its exceptional biocompatibility. Subsequently, the optimal reaction conditions and adsorption performance of MAT@MIPs were systematically investigated. The obtained polymers were characterized and evaluated by Fourier transform infrared spectrometry, scanning electron microscopy, elemental analysis, and thermogravimetric analysis. Results indicated that the MIPs demonstrated a favorable imprinting factor (2.36) and a high binding capacity (21.48 mg·g−1) for matrine. In vitro studies, we performed cell counting kit-8 assays in HepG2 cells, then the drug delivery capabilities of MAT-loaded MIPs were validated through light microscopy analyses, and the matrine content in culture medium was quantified using ultra high-performance liquid chromatography-mass spectrum synchronously. The facile fabrication of MAT@MIPs presents a viable solution for designing high-loading and pH-responsive DDS, which can offer a novel administration approach for drugs requiring injection in clinical applications.

Advances in the application of logic gates in nanozymes.

Nanozymes are a class of nanomaterials with biocatalytic function and enzyme-like activity, whose advantages include high stability, low cost, and mass production. They can catalyze the substrates of natural enzymes based on specific nanostructures and serve as substitutes for natural enzymes. Their applied research involves a wide range of fields such as biomedicine, environmental governance, agriculture, and food. Molecular logic gates are a new cross-disciplinary discipline, which can simulate the function of silicon circuits on a molecular scale, perform single or multiple input logic operations, and generate logic outputs. A molecular logic gate is a binary operation that converts an input signal into an output signal according to the rules of Boolean logic, generating two signals, a high level, and a low level. The high and low levels represent the "true" and "false" values of the logic gates, and their outputs correspond to "l" and "0" of the molecular logic gates, respectively. The combination of nanozymes and logic gates is a novel and attractive research direction, and the cross-application of the two brings new opportunities and ideas for various fields, such as the construction of efficient biocomputers, intelligent drug delivery systems, and the precise diagnosis of diseases. This review describes the application of logic gates based on nanozymes, which is expected to provide a certain theoretical foundation for researchers' subsequent studies.

Thrombotic microenvironment responsive crosslinking cyclodextrin metal-organic framework nanocarriers for precise targeting and thrombolysis

Global public health is seriously threatened by thrombotic disorders because of their high rates of mortality and disability. Most thrombolytic agents, especially protein-based pharmaceuticals, have a short half-life in circulation, reducing their effectiveness in thrombolysis. The creation of an intelligent drug delivery system that delivers medication precisely and releases it under regulated conditions at nearby thrombus sites is essential for effective thrombolysis. In this article, we present a unique medication delivery system (MCRUA) that selectively targets platelets and releases drugs by stimulation from the thrombus' microenvironment. The thrombolytic enzyme urokinase-type plasminogen-activator (uPA) and the anti-inflammatory medication Aspirin (acetylsalicylic acid, ASA) are both loaded onto pH-sensitive CaCO3/cyclodextrin crosslinking metal-organic frameworks (MC) that make up the MCRUA system. c(RGD) is functionalized on the surface of MC, which is functionalized by RGD to an esterification reaction. Additionally, the thrombus site's acidic microenvironment causes MCRUA to disintegrate to release uPA for thrombolysis and aiding in vessel recanalization. Moreover, cyclodextrin-encapsulated ASA enables the treatment of the inflammatory environment within the thrombus, enhancing the antiplatelet aggregation effects and promoting cooperative thrombolysis therapy. When used for thrombotic disorders, our drug delivery system (MCRUA) promotes thrombolysis, suppresses rethrombosis, and enhances biosafety with fewer hemorrhagic side effects.

Injectable Chitosan Hydrogels Doped with 2D Peptide Nanosheet-Drug Conjugates for Glutathione-Responsive Sustained Drug Delivery.

The development of novel and effective drug delivery systems aimed at enhancing therapeutic profile and efficacy of therapeutic agents is a critical challenge in modern medicine. This study presents an intelligent drug delivery system based on self-assembled two-dimensional peptide nanosheets (2D PNSs). Leveraging the tunable properties of amino acid structures and sequences, we design a peptide with the sequence of Fmoc-FKKGSHC, which self-assembles into 2D PNSs with uniform structure, high biocompatibility, and excellent degradability. Covalent attachment of thiol-modified doxorubicin (DOX) drugs to 2D PNSs via disulfide bonds results in the peptide-drug conjugates (PDCs), which is denoted as PNS-SS-DOX. Subsequently, PDCs are encapsulated within the injectable, thermosensitive chitosan (CS) hydrogels for drug delivery. The designed drug delivery system demonstrates outstanding pH-responsiveness and sustained drug release capabilities, which are facilitated by the characteristics of the CS hydrogels. Meanwhile, the covalently linked disulfide bond within PNS-SS-DOX is responsive to the intracellular glutathione (GSH) within tumor cells, enabling controlled drug release and significantly inhibiting cancer cell growth. This responsive peptide-drug conjugate based on a 2D peptide nanoplatform paves the way for the development of smart drug delivery systems and has bright prospects in the future biomedicine field.

Photoinduced Metal-Free Atom Transfer Radical Polymerization for the Modification of Cellulose with Poly(N-isopropylacrylamide) to Create Thermo-Responsive Injectable Hydrogels.

Photoinduced metal-free ATRP has been successfully applied to fabricate thermo-responsive cellulose graft copolymer (PNIPAM-g-Cell) using 2-bromoisobuturyl bromide-modified cellulose as the macroinitiator. The polymerization of N-isopropylacrylamide (NIPAM) from cellulose was efficiently activated and deactivated with UV irradiation in the presence of an organic-based photo-redox catalyst. Both FTIR and 13C NMR analysis confirmed the structural similarity between the obtained PNIPAM-g-Cell and that synthesized via traditional ATRP methods. When the concentration of the PNIPAM-g-Cell is over 5% in water, it forms an injectable thermos-responsive hydrogel composed of micelles at 37 °C. Since organic photocatalysis is a metal-free ATRP, it overcomes the challenge of transition-metal catalysts remaining in polymer products, making this cellulose-based graft copolymer suitable for biomedical applications. In vitro release studies demonstrated that the hydrogel can continuously release DOX for up to 10 days, and its cytotoxicity indicates that it is highly biocompatible. Based on these findings, this cellulose-based injectable, thermo-responsive drug-loaded hydrogel is suitable for intelligent drug delivery systems.

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.

Smart Ultrasound-responsive Polymers for Drug Delivery: An Overview on Advanced Stimuli-sensitive Materials and Techniques.

In recent years, a notable advancement has occurred in the domain of drug delivery systems via the integration of intelligent polymers that respond to ultrasound. The implementation of this groundbreaking methodology has significantly revolutionised the controlled and precise delivery of therapeutic interventions. An in-depth investigation is conducted into the most recent developments in ultrasonic stimulus-responsive materials and techniques for the purpose of accomplishing precise medication administration. The investigation begins with an exhaustive synopsis of the foundational principles underlying drug delivery systems that react to ultrasonic stimuli, focusing specifically on the complex interplay between polymers and ultrasound waves. Significant attention is devoted to the development of polymers that demonstrate tailored responsiveness to ultrasound, thereby exemplifying their versatility in generating controlled drug release patterns. Numerous classifications of intelligent polymers are examined in the discussion, including those that react to variations in temperature, pH, and enzymes. When coupled with ultrasonic stimuli, these polymers offer a sophisticated framework for the precise manipulation of drug release in terms of both temporal and spatial dimensions. The present study aims to examine the synergistic effects of responsive polymers and ultrasound in overcoming biological barriers such as the blood-brain barrier and the gastrointestinal tract. By doing so, it seeks to shed light on the potential applications of these materials in intricate clinical scenarios. The issues and future prospects of intelligent ultrasound-responsive polymers in the context of drug delivery are critically analysed in this article. The objective of this study is to offer valuable perspectives on the challenges that must be overcome to enable the effective implementation of these technologies. The primary objective of this comprehensive review is to furnish researchers, clinicians, and pharmaceutical scientists with a wealth of information that will serve as a guide for forthcoming developments in the development and enhancement of intelligent drug delivery systems that employ ultrasound-responsive polymers to attain superior therapeutic outcomes.

Preparation of pH-responsive polyurethane nano micelles and their antibacterial application

Considering the differences in pH between bacterial infection microenvironment and normal tissues, a series of pH-responsive drug-release amphiphilic polyurethane copolymers (DPU-g-PEG) have been prepared in this work. Fourier transform infrared (FT-IR) spectroscopy and 1H NMR was selected to detect the structure of the condensed polymers. The DPU-g-PEG amphiphilic copolymers could form stable micelles with a hydrophilic shell of polyethylene glycol (PEG) and a hydrophobic core of polylactic acid (PLA). We loaded a model drug called triclosan onto DPU-g-PEG micelles and studied how pH affects their particle size, Zeta potential, and drug release performance. The results revealed that when exposed to acidic conditions, the surface potential of DPU-g-PEG micelles changed, the micelles’ particle size increased, and the drug release performance was significantly enhanced. These results suggested that the micelles prepared in this study can release more antibacterial substances at sites of bacterial infection. Meanwhile, we also investigated the impact of different ratios of soft and hard segments on the properties of micelles, and the results showed that the pH responsiveness of micelles was strongest when the ratio of soft segments (PLLA diol + PEG 2000): 1,6-hexamethylene diisocyanate (HDI): 2,6-Bis-(2-hydroxy-ethyl)-pyrrolo[3,4-f]isoindole-1,3,5,7-tetraone (DMA) = 1: 1.2: 0.2. Furthermore, the results of inhibition zone test, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) all confirmed the antibacterial activity of triclosan-load DPU-g-PEG micelles. In conclusion, the DPU-g-PEG micelles produced in this study have the potential to be used as intelligent drug delivery systems in the biomedical field.

ROS-responsive polymeric micelles with aggregation-induced emission effects for drug delivery and cellular imaging

The ROS-responsive amphiphilic copolymer micelles mPEG-TK-PCL-TPE, combined with AIE properties, enable real-time drug release monitoring and intracellular tracing, and ensures stable circulation and rapid release in tumors.

Intelligent Delivery Systems in Tumor Metabolism Regulation: Exploring the Path Ahead.

Cancer metabolism plays multifaceted roles in the initiation and progression of tumors, and interventions in metabolism are considered fundamental approaches for cancer control. Within the vast metabolic networks of tumors, there exist numerous potential therapeutic targets, intricately interconnected with each other and with signaling networks related to immunity, metastasis, drug resistance, and more. Based on the characteristics of the tumor microenvironment, constructing drug delivery systems for multi-level modulation of the tumor microenvironment is proven as an effective strategy for achieving multidimensional control of cancer. Consequently, this article summarizes several features of tumor metabolism to provide insights into recent advancements in intelligent drug delivery systems for achieving multi-level regulation of the metabolic microenvironment in cancer, with the aim of offering a novel paradigm for cancer treatment.

Artificial Intelligence in Pharmaceutical Industry: Revolutionizing Drug Development and Delivery

Abstract: Artificial Intelligence (AI) has ushered in a profound revolution within the pharmaceutical sector, effectively streamlining the processes of drug development and delivery. The application of AI-driven tools and methodologies, including machine learning and natural language processing, in the realm of pharmaceutical research and development has yielded recent breakthroughs. This accelerated the drug discovery process by meticulously scrutinizing copious data and pinpointing potential drug targets, as expounded upon in this comprehensive review. Furthermore, AI has found utility in optimizing clinical trials, thereby refining trial designs and cost-effectiveness and bolstering patient safety. Notably, AI-based strategies are being harnessed to enhance drug delivery, fostering the creation of intelligent drug delivery systems engineered to target specific cells or organs. This results in heightened efficacy and a concomitant reduction in undesirable side effects. This review also delves into the potential biases residing within AI algorithms and the challenges associated with data quality when integrating AI into the pharmaceutical sphere. The findings of this study underscore the immense potential of artificial intelligence in reshaping the pharmaceutical industry, thereby enhancing the quality of life for patients worldwide.

Thermoresponsive MXene-based hydrogel for controlled anticancer drug release

The response of smart hydrogels to near-infrared (NIR) light has great potential for local drug delivery in tumor treatment. However, it is limited in biomedical applications due to low photothermal conversion rate, poor photothermal stability, and unreasonable temperature range. To solve this problem, we simply prepared a MXene/Gellan gum hydrogel (MXene@GG) by physically mixing MXene nanosheets, FeCl2 solution, and GG, which has high photothermal conversion efficiency and good photothermal stability. Importantly, MXene@GG have better photothermal properties than MXene solutions, can more effectively control drug release, and can easily control drug on/off release and kinetics. In addition, further cell experiments showed that the MXene@GG had good biocompatibility and that the drugs of doxorubicin (DOX) retained anticancer activity after rapid release from the MXene@GG hydrogel network under NIR irradiation. Thus, this newly prepared NIR responsive MXene@GG hydrogel provides a new approach for the development of intelligent drug delivery systems for local cancer treatment.

Temperature and pH-dependent nanogel for smart pesticide delivery with enhanced foliar dispersion and washout resistance can effectively control multiple plant diseases

The utilization of nanomaterials to develop a system capable of regulating pesticide release in response to environmental cues, enhancing the deposition efficacy on plant leaves, and increasing resistance against rainwater erosion holds immense significance in improving the efficiency of pesticide usage while minimizing residual pollution. Cellulose-based green nanocomposites have emerged as a promising candidate for intelligent drug delivery systems. In this study, we had successfully developed a novel biocompatible interpenetrating polymer network (IPN) gel, named SPCs, by incorporating sodium alginate (SA), polydopamine (PDA), and cellulose nanocrystal (CNC), and a stable gel-like network structure emulsion (MJ@SPCs) was achieved by coating the pesticide azoxystrobin (MJ). The resulting MJ@SPCs exhibited excellent pH responsiveness and temperature sensitivity. Compared to free MJ, MJ@SPCs exhibited improved foliar wettability, rain erosion resistance, deposition rate, and controlled release performance. The results of the bacteriostatic performance test indicated that MJ@SPCs exhibited a higher inhibitory efficiency against Gibperella zeae (GZ) than MJ at equivalent concentrations. Moreover, the in vivo biosafety evaluation of MJ@SPCs had confirmed its relative safety for aquatic zebrafish. This study offers insights into the potential applications of nanopesticides for sustainable plant protection.

The novel design of an intelligent anti-depression transdermal drug delivery system

Depression is a type of mental disorder with a significant and persistent low mood as the main clinical feature. It is often accompanied by symptoms such as slow thinking, decreased will, loss of appetite, and weight loss. The current treatment methods for depression are mainly medical treatment, psychotherapy, and physical therapy. These treatments are dependent on the patient's autonomy and the patients may suspend treatment due to forgetting or refusing. Therefore, an anti-depressant intelligent drug release system was designed, which can achieve autonomously controlled doses for the treatment of depression by transdermal drug delivery system. The work of this study is as follows:(1) The first module: the electrothermal material heating layer. Several preparation methods were screened, and multiple sets of graphene (GE) electric thermogenic layers were successfully prepared. After increasing the actual energization area to 1 cm × 1 cm, the GE electric thermogenic layer is used as the heating layer of the electrothermal material of the system, and can reach a uniform surface temperature of (45 ± 0.5) °C within 15 s at a voltage of 6 V keeping the temperature fluctuation range not exceeding ±0.03 °C, and the resistance fluctuation range not exceeding ±20 Ω, which plays a role in controlling the temperature and heat treatment of the drug loaded gel layer.(2) The second module: the drug-loaded gel layer. Based on the L16 (45) orthogonal test, the best formulation and process of N-Isopropyl acrylamide-Acrylamide copolymer (P(NIPAAm-co-AAm)) hydrogel was determined. Then, the percutaneous permeability of Selegiline liposome was studied in vitro.(3) A rat model of depression was established using chronic unpredictable mild stress (CUMS) combined with separation. From the aspects of behavior (body weight, sucrose preference test, forced swimming test, open field test) and biochemical indexes (serum proinflammatory cytokines (IL-1β, TNF-α), hippocampus HE staining observation), the therapeutic effect of hyperthermia, Selegiline oral administration and transdermal administration was discussed.

A targeted drug delivery system based on E. coli ghost for inhibiting non-Hodgkin’s lymphoma

Doxorubicin (DOX) is extensively utilized in the treatment of aggressive lymphomas, while its significant toxic side effects hamper its clinical application. Hence, there is an urgent need for a safe and effective antilymphoma drug delivery system at this stage. This study successfully developed an optimal drug delivery system (R-PEG@BGs-DOX) to safe and efficient delivery of DOX to non-Hodgkin's lymphoma site. The R-PEG@BGs-DOX was prepared by modifying polyethylene glycol (PEG) and Rituximab (R) onto the surface of bacterial ghosts (BGs), which were obtained through NaOH treatment of E. coli BL21 with modulation to achieve target structures. The prepared R-PEG@BGs exhibited efficient loading of DOX, demonstrating excellent targeting properties. The R-PEG@BGs-DOX can significantly inhibit the growth of non-Hodgkin's lymphoma cells while showing minimal toxic side effects on normal tissues. These results strongly suggest that R-PEG@BGs-DOX holds great promise as an intelligent, safe, and effective drug delivery system for anti-lymphoma treatment.

PH-responsive double emulsion system for targeted anticancer therapy based on polyacrylic acid-polyvinyl pyrrolidone containing carbon nanotubes for 5-fluorouracil as an anticancer medication

The second most significant cause of death among females is considered as breast cancer. Nowadays, many treatments are used to stop and control cancerous cells; among all, chemotherapy and anticancer medications have been applied to most patients for a long time. Although these methods successfully treat cancer, various harmful and unwanted side effects increase pain and suffering for the patients, including drug resistance, high toxicity, and non-targeting. Among different chemotherapy medications, 5-FU is one of the famous chemotherapeutic medications used to treat multiple tumors for over 70 years. With nanomaterials' help, intelligent drug delivery systems have been provided to carry different anticancer medications with minimal side effects. CNTs are well-known nanoparticles that could be used as carriers for smart drug delivery systems. Having an appropriate porosity, low toxicity, and transport, and regulating the amount of drug released make CNTs a suitable candidate as carriers in drug delivery systems. In this work, a combination of CNT nanoparticleswith PAA and PVP polymers was used to fabricate CNT/PAA/PVP nanocomposite as a drug delivery system, and 5-FU was encapsulated in the synthesized nanocarrier as an anticancer medication against MCF-7 breast cancer cell line with double emulsion technique (W-O-W). FT-IR and XRD analyses have been used to investigate different physical interactions and the crystalline behavior of the nanocomposite particles, respectively. DLS and Zeta potential identified nanoemulsions' average size distribution and surface charge. FESEM images were used to investigate the morphology features of the nanocarrier. The encapsulation and loading efficiency in CNT-PAA-PVP@5-FU nanocomposite was around 88.00 % and 45.5 %, respectively. The release pattern of 5-FU in the nanocomposite in the neutral and acidic conditions followed Korsmeyer-Peppas and Higuchi kinetic models, respectively. The pattern also proved that the release was pH-dependent and controlled in various media. MTT test verified a good cytotoxicity for the nanocomposite, and flow cytometry showed that the apoptotic percentage against MCF-7 in the nanocarrier was higher than free 5-FU. In light of these findings, the CNT-PAA-PVP@5-FU drug delivery system can be used to transport pharmaceuticals to cancerous tumors with fewer side effects compared to old treatments.

Multi-Stimuli-Responsive Nanoparticles Formed of POSS-PEG for the Delivery of Boronic Acid-Containing Therapeutics.

Polymeric vehicles often exhibit batch-to-batch variations due to polydispersity, limiting their reproducibility for biomedical applications. In contrast, polyhedral oligomeric silsesquioxane (POSS) has emerged as an attractive candidate for drug delivery due to its precise chemical structure and rigid molecular shape. A promising strategy to enhance drug efficacy while reducing systemic toxicity is the development of multi-stimuli-responsive delivery systems capable of targeted drug release at a disease site. Herein, we developed a drug delivery platform based on POSS-polymer conjugates. By functionalizing the POSS with amino groups and establishing B-N coordination with boronic acids, the nanoparticles (NPs) exhibit responsive behavior to stimuli, including adenosine-5'-triphosphate (ATP), acidic pH, and nucleophilic reagents. We successfully encapsulated two boronic acid-containing molecules: tetraphenylethylene (TPE), serving as a fluorescent probe, and bortezomib (BTZ), an anticancer drug. The TPE@NPs were employed to visualize the cellular uptake of NPs by tumor cells, while the BTZ@NPs exhibited increased cytotoxicity in tumor cells compared with normal cells. This POSS-PEG conjugate offers a nanoparticle platform for encapsulating versatile boronic acid-containing molecules, thereby enhancing drug efficacy while minimizing systemic toxicity. Given the wide-ranging applications of boronic acid-containing molecules in biomedicine, our platform holds significant promise for the development of intelligent drug delivery systems for diagnostics and therapeutics.