Smart Nanogels Research Articles

Fabrication of smart nanogel based on carrageenan and green coffee extract as a long-term antifouling agent to improve biofilm prevention in food production

This study investigates the extract of the bioactive compounds from green coffee extract (GCE) and the loading of two different concentrations of GCE (1% and 2%) onto carrageenan nanogels (CAR NGs) to compare their antibacterial and antibiofilm effects with unloaded nanogels (NGs). The bioactive compounds of GCE were characterized using GC–MS analysis. The GCE1 and GCE2 were successfully deposited onto the surface of CAR NGs. The antibacterial and antibiofilm potential of prepared NGs were conducted against some foodborne pathogens (E. coli O157, Salmonella enterica, Staphylococcus aureus, and Listeria monocytogenes). The results of GC–MS analysis indicated that there were identified 16 bioactive compounds in GCE, including caffeine (36.27%), Dodemorph (9.04%), and D-Glycero-d-ido-heptose (2.44%), contributing to its antimicrobial properties. The antibacterial coatings demonstrated a notable antimicrobial effect, showing zone of inhibition (ZOI) diameters of up to 37 mm for GCE2 loaded CAR NGs. The minimum inhibitory concentration (MIC) values for GCE2 loaded CAR NGs were 80 ppm for E. coli O157, and 120 ppm for S. enterica, S. aureus, and L. monocytogenes, achieving complete bacterial inactivation within 10–15 min of exposure. Both GCE1 and GCE2 loaded CAR NGs significantly reduced biofilm cell densities on stainless steel (SS) materials for E. coli O157, S. enterica, S. aureus, and L. monocytogenes, with reductions ranging from 60% to 95%. Specifically, biofilm densities were reduced by up to 95% for E. coli O157, 89% for S. enterica, 85% for S. aureus, and 80% for L. monocytogenes. Results of the toxicity evaluation indicated that the NGs were non-toxic and biocompatible, with predicted EC50 values proved their biocompatibility and safety. These results recommended that GCE loaded CAR NGs are promising as natural antimicrobial agents for enhancing food safety and extending shelf life. Further, the study concluded that incorporating GCE into CAR NGs is an effective strategy for developing sustainable antimicrobial coatings for the food industry and manufacturing.

In situ tumor vaccine with optimized nanoadjuvants and lymph node targeting capacity to treat ovarian cancer and metastases

Tumor vaccine, a promising modality of tumor immunotherapy, needs to go through the process of tumor antigen generation and loading, antigen drainage to lymph nodes (LNs), antigen internalization by dendritic cells (DCs), DC maturation, and antigen cross-presentation to activate T-cells. However, tumor vaccines are often unable to satisfy all the steps, leading to the limitation of their application and efficacy. Herein, based on a smart nanogel system, an in situ nano-vaccine (CpG@Man-P/Tra/Gel) targeting LNs was constructed to induce potent anti-tumor immune effects and inhibit the recurrence and metastasis of ovarian cancer. The CpG@Man-P/Tra/Gel exhibited MMP-2-sensitive release of trametinib (Tra) and nano-adjuvant CPG@Man-P, which generated abundant in situ depot of whole-cell tumor antigens and formed in situ nano-vaccines with CpG@Man-P. Benefiting from mannose (Man) modification, the nano-vaccines targeted to LNs, promoted the uptake of antigens by DCs, further inducing the maturation of DCs and activation of T cells. Moreover, CpG@Man-P with different particle sizes were prepared and the effective size was selected to evaluate the antitumor effect and immune response in vivo. Notably, combined with PD-1 blocking, the vaccine effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis of ovarian cancer.

Natural Polymer-Based Nanogel for pH-Responsive Delivery of Sorafenib Tosylate in Hemangiosarcoma.

Smart nanomedicinal treatment for cancer manifests a solubility challenge with inherent nanoscale size and nonspecific release with stimuli-responsive potential. This is the limelight in novel chemotherapy to pursue physiochemical differences between the tumor microenvironment (TME) and normal cells, which introduces active groups of nanocarriers responding to various stimuli, endowing them with concise responses to various tumor-related signals. The nanogels were successfully prepared by a modified solvent evaporation technique. Nine batches were formulated by changing the chitosan concentration (12, 14, 16mg/ml) and sonication time (5, 10, 15min). The formulations were optimized for particle size and zeta potential with high percent entrapment efficiency (%EE) through Central Composite Design software. The optimized batch F7 had a 182-nm size and high zeta potential (64.5mV) with 98% EE. The drug release of F7 was higher at pH 6 (97.556%) than at pH 7.4 (45.113%). The pharmacokinetic study shows that the release follows the Hixon plot model (R2 = 0.9334) that shifts to zero order (R2 = 0.9149). The nanogel F7 was observed for stability and showed an absence of color change, phase separation, and opacity for 6months. In the present study, the pH difference between cancer cells and normal cells is the key point of the smart nanogel. This study is promising but challenging depending on the in vivo study. The nanogel was successfully prepared and evaluated for pH-responsive release. As hemangiosarcoma commonly occurs in dogs, this formulation helps to limit the difficulties with administration.

Photo-responsive doxorubicin delivery: Nanogel systems based on azobenzene and host-guest interactions enhanced by squeezing action

Conventional chemotherapy methods impact both normal and cancerous cells; therefore, it is essential to design drug delivery systems to reduce undesired drug effects. Nano-scaled drug delivery systems have the advantage of high retention time in blood as well as the capability of conventional penetration into tissue barriers. In this study, light-sensitive biocompatible nanogels with a core-shell structure have been synthesized and characterized as drug delivery system loaded with doxorubicin (DOX). These smart nanogels possess a hydrophobic core, coated with hydrophilic starch polymeric chains, which are modified with β-cyclodextrin (βCD). The core-shell formation is based on host-guest interaction between azobenzene rings as photochromic agents and βCD hydrophobic cavities. The mechanism of drug release is based on the cis-trans isomerization of azobenzene molecules upon light irradiation and dissociation of crore-shell entities. Due to this isomerization, shrinkage of hydrophobic core and removal of shell occurred simultaneously, which assist the drug release. In conclusion, a nanoscale carrier was designed with sustainable drug release under light irradiation as an external and non-contact stimulus. The synthesized nanogels were characterized by FT-IR, 1H NMR, SEM, DLS, and TEM. In addition, the MTT assay proposed that the viability of the A-431 cells has plunged in the presence irradiated nanogels, also histological studies were performed to evaluate the efficacy of the prepared nanogels in cancerous tissues.

Near-infrared light-activated smart nanogels for remotely controlled cytochrome c release and photodynamic therapy

The utilization of reactive oxygen species (ROS) generated through photodynamic therapy (PDT) for remote-controlled release of protein drugs at specific sites using near-infrared light represents a groundbreaking development in protein delivery system innovation. To illustrate this principle, we engineered near-infrared light-activated smart nanogels (NASNs) by chemically cross-linking ROS-responsive linkages within hyaluronic acid-graft-methoxy poly(ethylene glycol)-diethylenetriamine-grafted-chlorine e6 (Ce6) polymer (HA-PEG-Dien-g-Ce6) and carboxylated thioketal (TK) serving as a cross-linker to enable PDT-driven cytochrome c (CC) liberation. The NASNs demonstrated substantial loading capacity and exceptional stability across diverse biological settings, attributed to the robust nature of the TK bond. Notably, CC-loaded NASNs effectively penetrated A549 cells via CD44-mediated endocytosis and rapidly escaped from the endo-lysosomal compartment. Upon light activation, the Ce6 produced ROS, leading to TK bond disruption in NASNs, and consequent release of encapsulated CC. This precise, photo-induced PDT mechanism and CC liberation markedly enhanced antitumor efficacy while maintaining minimal toxicity, establishing a solid foundation for remote, as-needed protein delivery systems and potential integration with additional therapeutic modalities.

Smart nanogels for cancer treatment from the perspective of functional groups.

Introduction: Cancer remains a significant health challenge, with chemotherapy being a critical treatment modality. However, traditional chemotherapy faces limitations due to non-specificity and toxicity. Nanogels, as advanced drug carriers, offer potential for targeted and controlled drug release, improving therapeutic efficacy and reducing side effects. Methods: This review summarizes the latest developments in nanogel-based chemotherapy drug delivery systems, focusing on the role of functional groups in drug loading and the design of smart hydrogels with controlled release mechanisms. We discuss the preparation methods of various nanogels based on different functional groups and their application in cancer treatment. Results: Nanogels composed of natural and synthetic polymers, such as chitosan, alginate, and polyacrylic acid, have been developed for chemotherapy drug delivery. Functional groups like carboxyl, disulfide, and hydroxyl groups play crucial roles in drug encapsulation and release. Smart hydrogels have been engineered to respond to tumor microenvironmental cues, such as pH, redox potential, temperature, and external stimuli like light and ultrasound, enabling targeted drug release. Discussion: The use of functional groups in nanogel preparation allows for the creation of multifunctional nanogels with high drug loading capacity, controllable release, and good targeting. These nanogels have shown promising results in preclinical studies, with enhanced antitumor effects and reduced systemic toxicity compared to traditional chemotherapy. Conclusion: The development of smart nanogels with functional group-mediated drug delivery and controlled release strategies represents a promising direction in cancer therapy. These systems offer the potential for improved patient outcomes by enhancing drug targeting and minimizing adverse effects. Further research is needed to optimize nanogel design, evaluate their safety and efficacy in clinical trials, and explore their potential for personalized medicine.

Current Advances in Stimuli-Responsive Hydrogels as Smart Drug Delivery Carriers.

In recent years, significant advancements in the field of advanced materials and hydrogel engineering have enabled the design and fabrication of smart hydrogels and nanogels that exhibit sensitivity to specific signals or pathological conditions, leading to a wide range of applications in drug delivery and disease treatment. This comprehensive review aims to provide an in-depth analysis of the stimuli-responsive principles exhibited by smart hydrogels in response to various triggers, such as pH levels, temperature fluctuations, light exposure, redox conditions, or the presence of specific biomolecules. The functionality and performance characteristics of these hydrogels are highly influenced by both their constituent components and fabrication processes. Key design principles, their applications in disease treatments, challenges, and future prospects were also discussed. Overall, this review aims to contribute to the current understanding of gel-based drug delivery systems and stimulate further research in this rapidly evolving field.

Designing of smart nanogels based on tragacanth gum for cisplatin delivery

AbstractThe present work deals with the development of smart nanogels with a coating of a lipid layer, which synergized the triggered delivery of the anticancer drug cisplatin (CP). In the first step, the chemical initiation method was used for the grafting of poly(itaconic acid) on tragacanth gum (TG). Subsequently, this grafted TG matrix was used for the synthesis of nanoparticles. Nanoemulsion process was followed to prepare CP‐loaded grafted TG–lecithin (GTG‐LC) nanogels using dioctyl sulfosuccinate as the surfactant. These nanoparticles were characterized for size, morphology, elemental composition and crystallinity. Transmission electron microscopy images of the GTG‐LC nanogels with varying concentrations of CP demonstrate an irregular polygonal shape of the nanoparticles which is strongly influenced by the CP concentration. The smart nanogels exhibit a unique structure, nano‐within‐nano, a structure where nanosized CP is encapsulated within the GTG‐LC nanogel. Grafted nanogels have a high carboxyl functionality and exhibit pH‐sensitive behavior leading to pH‐responsive drug release behavior. These nanogels show required biocompatibility and offer interesting material for nanomedicines in chemotherapy. © 2022 Society of Industrial Chemistry.

Development and biological evaluation of pNIPAM-based nanogels as vaccine carriers

“Smart” nanogels are an attractive tool for the development of new strategies of immunization in veterinary medicine. Here, we reported the synthesis and physicochemical characterization of thermoresponsive nanogels based on poly(N-isopropylacrylamide) (pNIPAM) and theirin vitro, ex vivoand in vivo (mice model) performance. Smart nanogels of ca. 250 nm, with a transition temperature of 32 °C were obtained by precipitation polymerization. Assays to evaluatepNIPAM nanogels cytotoxicity were performed in different cell lines showing high biocompatibility (>70 %). The efficient internalization of the system was studied by confocal microscopy as well as flow cytometry. The ability to protect and deliver antigens was analyzed using the outer membrane lipoprotein A (OmlA), an important virulence factor ofActinobacillus pleuropneumoniae(App)cause of porcine pleuropneumonia. This lipoprotein was synthesized by recombinant technology and its technique was also described. The biodistribution ofpNIPAM nanogels administered intranasally was performedinvivo and ex vivo through Pearl Imaging System, which showed that nanogels were kept mostly in the lungs during the evaluated time. Besides, the efficacy of the proposal nanogel-based vaccine was studiedin vivoby measuring the antibody titers of BALB/c mice inoculated with OmlA encapsulated intopNIPAM nanogels compared to OmlA plus aluminum hydroxide adjuvant. The results proved the ability of nanogels to stimulate a humoral immune response. Therefore, we have demonstrated thatpNIPAM nanogels can be used as an efficient platform for vaccine nanocarriers.

Design of a thermosensitive ibuprofen-loaded nanogel as smart material applied as anti-inflammatory in tooth bleaching: An in vivo study

The in vivo ability of thermosensitive nanogel containing ibuprofen for bioadhesion on the surface of teeth submitted to bleaching and drug delivery through dentinal tubules to the dental pulp are evaluated in Wistar rats. Drug-loaded self-assembled oil in water nanoemulsions present droplet size <150 nm and negative zeta potential. Nanoemulsions containing poloxamer 407 in the aqueous phase exhibit reduced droplet size, improved physical stability, controlled the thermosensitive viscosity, and slow drug release. Different treated animals' groups included a control group (CTRL); bleached animals (BLE) (37.5% H2O2, Pola Office Plus®, SDI); bleached animals treated with a conventional ibuprofen-loaded hydrogel (BLE + IBF-GEL), and bleached animals treated with thermosensitive ibuprofen-loaded nanogel (BLE + IBF-NEG). Compared to the BLE + IBF-GEL group, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) images show the superior ability of BLE + IBF-NEG group to offer a physical barrier on the tooth surface, pores occlusion, and transport the fluorescent dye rhodamine B to dental pulp. Morphological analysis revealed the lowest inflammatory infiltrate scores and absence of necrosis for BLE + IBF-NEG group after 24 h and 14 days. Immunohistochemical studies reinforced this hypothesis. The experimental data presented in this study confirm the incredible potential for topical and easy application of a novel and smart nanogel, as analgesic and anti-inflammatory treatment for bleaching procedure.

PH and reduction dual-responsive feather keratin - sodium alginate nanogels with high drug loading capacity for tumor-targeting DOX delivery

As a natural polymer, there are a lot of functional groups on the keratin molecular chains, such as carboxyl, amino and hydroxyl groups. In the present study, we used keratin (K) as a multifunctional crosslinker and prepared smart nanogels. The nanogels had high loading capacity for drug, while low drug leakage. The surface of the DOX@K/SA-NG is negatively charged and the size was determined to be 432 nm. The nanogels had drug loading capacity (DLC) of 65.2% (w/w) and were capable of triggering drug release upon both pH and reductive (glutathione (GSH)) environment while stable under physiological conditions (pH 7.4 + 10 μM GSH). We evaluated its cancer treatment performance through cell uptake and cytotoxicity experiments, it showed that the prepared DOX@K/SA-NG can effectively inhibit the growth of HepG2 cancer cells.

Nano-encapsulation of hydroxytyrosol into formulated nanogels improves therapeutic effects against hepatic steatosis: An in vitro study

Nanomaterials hold promise as a straightforward approach for enhancing the performance of bioactive compounds in several healthcare scenarios. Indeed, nanoencapsulation represents a valuable strategy to preserve the bioactives, maximizing their bioavailability. Here, a nanoencapsulation strategy for the treatment of nonalcoholic fatty liver disease (NAFLD) is presented. NAFLD represents the most common chronic liver disease in Western societies, and still lacks an effective therapy. Hydroxytyrosol (HT), a naturally occurring polyphenol, has been shown to protect against hepatic steatosis through its lipid-lowering, antioxidant and anti-inflammatory activities. However, the efficient delivery of HT to hepatocytes remains a crucial aspect: the design of smart nanogels appears as a promising tool to promote its intracellular uptake. In this paper, we disclose the synthesis of nanogel systems based on polyethylene glycol and polyethyleneimine which have been tested in an in vitro model of hepatic steatosis at two different concentrations (0.1 mg/mL and 0.5 mg/mL), taking advantage of high-content analysis tools. The proposed HT-loaded nanoscaffolds are non-toxic to cells, and their administration showed a significant decrease in the intracellular triglyceride levels, restoring cell viability and outperforming the results achievable with HT in its non-encapsulated form. Moreover, nanogels do not induce oxidative stress, thus demonstrating their biosafety. Overall, the formulated nanogel system achieves superior performance compared to conventional drug administration routes and hence represents a promising strategy for the management of NAFLD.

An improved method in fabrication of smart dual-responsive nanogels for controlled release of doxorubicin and curcumin in HT-29 colon cancer cells

The combination therapy which has been proposed as the strategy for the cancer treatment could achieve a synergistic effect for cancer therapies and reduce the dosage of the applied drugs. On account of the the unique properties as the high absorbed water content, biocompatibility, and flexibility, the targeting nanogels have been considred as a suitable platform. Herein, a non-toxic pH/thermo-responsive hydrogel P(NIPAAm-co-DMAEMA) was synthesized and characterized through the free-radical polymerization and expanded upon an easy process for the preparation of the smart responsive nanogels; that is, the nanogels were used for the efficient and controlled delivery of the anti-cancer drug doxorubicin (DOX) and chemosensitizer curcumin (CUR) simultaneously like a promising strategy for the cancer treatment. The size of the nanogels, which were made, was about 70 nm which is relatively optimal for the enhanced permeability and retention (EPR) effects. The DOX and CUR co-loaded nanocarriers were prepared by the high encapsulation efficiency (EE). It is important to mention that the controlled drug release behavior of the nanocarriers was also investigated. An enhanced ability of DOX and CUR-loaded nanoformulation to induce the cell apoptosis in the HT-29 colon cancer cells which represented the greater antitumor efficacy than the single-drug formulations or free drugs was resulted through the In vitro cytotoxicity. Overall, according to the data, the simultaneous delivery of the dual drugs through the fabricated nanogels could synergistically potentiate the antitumor effects on the colon cancer (CC).

Visual detection of trace lead(II) using a forward osmosis-driven device loaded with ion-responsive nanogels

A simple and portable thermometer-type device based on forward osmosis-driven liquid column rising is developed for visual detection of trace Pb2+. The device consists of a top indicator tube, a chamber loaded with Pb2+-responsive poly(N-isopropylacrylamide-co-benzo-18-crown-6-acrylamide) (PNB) smart nanogels and a bottom semipermeable membrane. Upon the recognition of Pb2+, PNB smart nanogels undergo a Pb2+-induced hydrophobic to hydrophilic transition, which simultaneously causes the increase of osmotic pressure inside the device. Driven by this osmotic pressure difference, more Pb2+ solution flows into the device, causing the rise of the liquid column in the indicator tube, which can be directly observed by naked eyes. The relationship between the change of liquid column height and the Pb2+ concentration is investigated for the quantitative detection of Pb2+. With the proposed forward osmosis-driven device, trace Pb2+ as low as 10−10 M in aqueous solutions can be detected. This method provides a novel and simple strategy for the visual detection of trace Pb2+.

Capsule membranes encapsulated with smart nanogels for facile detection of trace lead(II) ions in water

A novel method based on capsule membranes encapsulated with smart nanogels is successfully developed for facilely detecting trace lead(II) (Pb2+) ions, which are hazardous to both human health and the environment because of their toxicity. The capsule membrane system is composed of a semi-permeable calcium alginate membrane and encapsulated poly(N-isopropylacrylamide-co-acryloylamidobenzo-18-crown-6) (PNB) nanogels. The semi-permeable membrane allows Pb2+ ions and water to pass through quickly, but rejects the encapsulated nanogels and polymers totally. As soon as Pb2+ ions appear in the aqueous environment and enter into the capsule, they can be specifically recognized by encapsulated PNB nanogels via forming 18-crown-6/Pb2+ complexes that cause a Pb2+-induced phase transition of PNB nanogels from hydrophobic to hydrophilic state. As a result, the osmotic pressure inside the capsule membrane increases remarkably, and thus the elastic capsule membrane isothermally swells upon the presence of Pb2+ ions in the environmental aqueous solution. The Pb2+-induced swelling degree of the capsule membrane is dependent on the concentration of Pb2+ ions ([Pb2+]) in water. Thus, the [Pb2+] value in water is able to be easily detected by directly measuring the Pb2+-induced isothermal swelling ratio of the capsule membrane, which we demonstrate by using 15 prepared capsule membranes arranged in a line. The Pb2+-induced swelling ratios of the capsule membrane groups are easily observed with the naked eye, and the detection limit of the [Pb2+] in water is 10-9 mol L-1. Such a proposed method provides an easy and efficient strategy for facile detection of trace threat analytes in water.

Smart Nanotherapeutic Targeting of Tumor Vasculature.

The past decades have witnessed the development of a field dedicated to targeting tumor vasculature for cancer therapy. In contrast to conventional chemotherapeutics that need to penetrate into tumor tissues for killing tumor cells, the agents targeting tumor vascular system have two major advantages: direct contact with vascular endothelial cells or the blood and less possibility to induce drug resistance because of high gene stability of endothelial cells. More specifically, various angiogenesis inhibitors (AIs) and vascular disrupting agents (VDAs) that block tumor blood supply to inhibit tumor progression, some of which have been applied clinically, have been described. However, off-target effects and high effective doses limit the utility of these formulations in cancer patients. Thus, new strategies with improved therapeutic efficacy and safety are needed for tumor vessel targeting therapy. With the burgeoning developments in nanotechnology, smart nanotherapeutics now offer unprecedented potential for targeting tumor vasculature. Based on specific structural and functional features of the tumor vasculature, a number of different nanoscale delivery systems have been proposed for cancer therapy. In this Account, we summarize several distinct strategies to modulate tumor vasculature with various smart nanotherapeutics for safe and effective tumor therapy developed by our research programs. Inspired by the blood coagulation cascade, we generated nanoparticle-mediated tumor vessel infarction strategies that selectively block tumor blood supply to starve the tumor to death. By specifically delivering thrombin loaded DNA nanorobots (Nanorobot-Th) into tumor vessels, an intratumoral thrombosis is triggered to induce vascular infarction and, ultimately, tumor necrosis. Mimicking the coagulation cascade, a smart polymeric nanogel achieves permanent and peripheral embolization of liver tumors. Considering the critical role of platelets in maintaining tumor vessel integrity, a hybrid (PLP-D-R) nanoparticle selectively depleting tumor-associated platelets (TAP) to boost tumor vessel permeability was developed for enhancing intratumoral drug accumulation. In addition, benefiting from a better understanding of the molecular and cellular underpinnings of vascular normalization, several tumor acidity responsive nanotherapeutics, encapsulating therapeutic peptides, and small interfering RNA were developed to correct the abnormal features of the tumor vasculature. This made the tumor vessels more efficient for drug delivery. While we are still exploring the mechanisms of action of these novel nanoformulations, we expect that the strategies summarized here will offer a promising platform to design effective next-generation nanotherapeutics against cancer and facilitate the clinical translation of smart nanotherapeutics that target tumor vasculature.

Temperature/pH-Triggered PNIPAM-Based Smart Nanogel System Loaded With Anastrozole Delivery for Application in Cancer Chemotherapy.

Thermo and pH-responsive poly-N-isopropylacrylamide (PNIPAM) polymer has gained interest due to microenvironment targeting potential toward cancer cells. Its exceptional potential of the phase transition at body temperature (37°C) makes it biologically relevant for drug delivery and biosensing. The optimum drug loading and particle size with controlled release at a specific site are essential for critical process parameters (CPP). This study investigates the formulation optimization anastrozole (ANST)-loaded PNIPAM nanoparticle (NPs) prepared by solvent evaporation method for pH- and thermo-responsive drug delivery. Box-Behnken design (BBD) was implemented to observe the effect of selected process parameters on quality attributes product including particle size 110.15nm, zeta potential - 11.02mV, PDI 0.175, and drug loading 8.35% (DL). The statistical data was found to fit in the quadratic model and p value is less than 0.005. The thermo-responsive behavior of PNIPAM is evaluated on DLS and UV-Visible spectroscopy at elevated temperature to 60°C that has shown increment in turbidity showed aggregation of the nanoparticles. The TEM and AFM revealed the spherical and smooth surface ANST-PNIPAM NPs. The formulation showed the controlled release of ANST for 48h at pH 7.4 and triggered release at simulated tumor microenvironment pH 5.0. The in vitro cytotoxicity of the formulation is higher than free ANST and shown dose-dependent cell viability. The higher cell uptake was observed by NPs after 12-h incubation in MCF-7 cell lines using confocal microscopy. Apoptotic evaluation of ANST-PNIPAM NPsexhibited 22.67% in comparison to free ANST where 6% was analyzed on the flow cytometer.

Different types of smart nanogel for targeted delivery

Abstract Decades of massive works have developed different carriers, lipoproteins, liposomes, ionic liquids, surfactants and nanogels, to enhance the targeted transportation of drugs, to reduce the side effects and to achieve controllable action on the curative sites. The word ‘nanogels’ is defined as the hydrogel nanoparticles with tunable size of 1–1000 nm formed by physical or chemical cross linked networks. The conventional challenges of solubility, substandard pharmacokinetics, in-vivo stability and toxicity, are being overcome by nanogels and other carriers. The reviewed nanogels in this article are purely based on pH, temperature, magnetic field, light and on combination of them. The discussed information will be very helpful to design a targeted delivery vehicle by specifically using photo-sensitive core-shell multi-sensitive nanogels.

Glutathione and pH‐responsive fluorescent nanogels for cell imaging and targeted methotrexate delivery

Cancer is one of the health problems that lead to death in the world, and nanotechnology was shown to have a unique potential to improve the therapeutic efficacy of anticancer agents. The nanosized drug delivery systems (DDSs) have been offered for targeting tumor tissue because of enhanced drug bioavailability and long circulation time. In this context, we reported a facial approach to prepare a novel pH and glutathione‐responsive nanogel. After that, the nanocarriers coupled with highly fluorescent quantum dots were developed. Then methotrexate (MTX) was loaded into and on the surface of nanogels by ionic interaction so that the triggered MTX release ability of the synthesized nanocarriers was verified through the assessment of in vitro drug release at simulated tumor tissue condition. The improved efficiency of the developed nanogels and their targeted performance via conjugation of MTX (as target ligand of folate receptors) were investigated through the various cell cytotoxicity studies such as 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, 4′6‐diamidino‐2‐phenylindole (DAPI) staining, and flow cytometry. The results of various cell cytotoxicity studies concluded that the developed smart nanogels have many promising abilities for the targeted MTX delivery to cancer tissues.

Supramolecular Nanogel‐Based Universal Drug Carriers Formed by “Soft–Hard” Co‐Assembly: Accurate Cancer Diagnosis and Hypoxia‐Activated Cancer Therapy

AbstractThe development of multifunctional drug delivery systems (DDSs) capable of carrying various drugs for diverse disease treatments is highly desirable yet remains challenging. Taking advantage of the excellent properties of silicon‐containing nanodots (SiNDs), a self‐traceable nanogel‐based DDS formed by the co‐assembly of a “soft” copolymer and a “hard” fluorescent SiND is developed, which has tunable size/fluorescence, high encapsulation efficiencies (60–92%) for various small molecule drugs, and pH‐responsive drug release capability. As a proof of concept, 5‐aminolevulinic acid, a hydrophilic prodrug of protoporphyrin IX (PpIX), and tirapazamine (TPZ), a water‐soluble hypoxia‐responsive drug, are successfully and stably encapsulated into the nanogels. The drug‐loaded green‐emissive nanogels achieve the selective biosynthesis of red‐fluorescent PpIX in tumors and can serve as a ratiometric probe for accurate cancer diagnosis. Moreover, the in situ synthesized PpIX can consume oxygen to produce toxic singlet oxygen in the tumor microenvironment under light irradiation, thus activating the hypoxia‐dependent cytotoxicity of TPZ. Thanks to the less PpIX production and the neutral/normoxic environment in normal tissues, the nanoagents elicit negligible toxicity to normal cells even under light irradiation. Overall, this work develops a novel strategy for constructing a series of smart nanogels as universal DDSs and realizes precision cancer theranostics.