Stimuli-responsive Drug Delivery Research Articles

Smart Chondroitin Sulfate Micelles for Effective Targeted Delivery of Doxorubicin Against Breast Cancer Metastasis.

Metastasis is a major challenge in breast cancer therapy. The successful chemotherapy of breast cancer largely depends on the ability to block the metastatic process. Herein, we designed a dual-targeting and stimuli-responsive drug delivery system for targeted drug delivery against breast cancer metastasis. AS1411 aptamer-modified chondroitin sulfate A-ss-deoxycholic acid (ACSSD) was synthesized, and the unmodified CSSD was used as the control. Chemotherapeutic drug doxorubicin (DOX)-containing ACSSD (D-ACSSD) micelles were prepared by a dialysis method. The ACSSD conjugate was confirmed by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). In vitro cellular uptake and cytotoxicity of D-ACSSD micelles were studied by confocal laser scanning microscopy (CLSM) and MTT assay in breast tumor cells. The inhibition capability of D-ACSSD micelles in cell migration and invasion was carried out in 4T1 cells. In vivo antitumor activity of DOX-containing micelles was investigated in metastatic 4T1-bearing Balb/c mice. D-ACSSD and DOX-loaded CSSD (D-CSSD) micelles exhibited high drug encapsulation content and reduction-responsive characteristics. D-ACSSD micelles were spherical in shape. Compared with D-CSSD, D-ACSSD showed higher cellular uptake and more potent killing activity in 4T1 and MDA-MB-231 cells. Additionally, D-ACSSD exhibited stronger inhibitory effects on the invasion and migration of highly metastatic 4T1 cells than unmodified D-CSSD. Among the DOX-containing formulations, D-ACSSD micelles presented the most effective inhibition of tumor growth and lung metastasis in orthotopic 4T1-bearing mice in vivo. It also revealed that ACSSD micelles did not exhibit obvious systemic toxicity. The smart D-ACSSD micelles could be a promising delivery system for the therapy of metastatic breast cancer.

Uniform Two-Dimensional Crystalline Platelets with Tailored Compositions for pH Stimulus-Responsive Drug Release.

Two-dimensional, size-tunable, water-dispersible particle micelles with spatially defined chemistries can be obtained by using "living" crystallization-driven self-assembly (CDSA) approach. Nevertheless, a major obstacle of crystalline particles in drug delivery application is the difficulty in accessing to cargo within crystalline cores. In the present work, we design four different types of biocompatible two-dimensional platelets with a crystalline poly(ε-caprolactone) (PCL) core, a hydrophobic poly(4-vinylprydine) (P4VP) segment, and a water dispersible poly(N,N-dimethyl acrylamide) (PDMA) block in ethanol by seeded growth method. Transferring those uniform platelets with tailored compositions to an aqueous solution in the presence of a hydrophobic drug leads to efficient encapsulation of the cargo in the P4VP segments via hydrophobic interactions. These drug-loaded platelets exhibit pH-responsive release behavior in aqueous media due to the protonated-deprotonated process of P4VP blocks in acidic and neutral solutions. This work provides initial insight into biocompatible PCL platelets with low dispersity and precise chemistry control in stimulus-responsive drug delivery fields.

"Smart" drug delivery: A window to future of translational medicine.

Chemotherapy is the mainstay of cancer treatment today. Chemotherapeutic drugs are non-selective and can harm both cancer and healthy cells, causing a variety of adverse effects such as lack of specificity, cytotoxicity, short half-life, poor solubility, multidrug resistance, and acquiring cancer stem-like characteristics. There is a paradigm shift in drug delivery systems (DDS) with the advent of smarter ways of targeted cancer treatment. Smart Drug Delivery Systems (SDDSs) are stimuli responsive and can be modified in chemical structure in response to light, pH, redox, magnetic fields, and enzyme degradation can be future of translational medicine. Therefore, SDDSs have the potential to be used as a viable cancer treatment alternative to traditional chemotherapy. This review focuses mostly on stimuli responsive drug delivery, inorganic nanocarriers (Carbon nanotubes, gold nanoparticles, Meso-porous silica nanoparticles, quantum dots etc.), organic nanocarriers (Dendrimers, liposomes, micelles), antibody-drug conjugates (ADC) and small molecule drug conjugates (SMDC) based SDDSs for targeted cancer therapy and strategies of targeted drug delivery systems in cancer cells.

A pH-Responsive Drug Delivery System Based on Conjugated Polymer for Effective Synergistic Chemo-/Photodynamic Therapy

Stimuli-responsive drug release and photodynamic therapy (PDT) have aroused extensive attention for their enormous potential in antitumor treatment. pH-responsive drug delivery systems (PFE-DOX-1 and PFE-DOX-2) based on water-soluble conjugated polymers were constructed in this work for high-performance synergistic chemo-/PDT therapy, in which the anticancer drug doxorubicin (DOX) is covalently attached to the side chains of the conjugated polymers via acid-labile imine and acylhydrazone bonds. Concurrently, the intense fluorescence of poly(fluorene-co-ethynylene) (PFE) is effectively quenched due to the energy/electron transfer (ET) between the PFE-conjugated backbone and DOX. Effective pH-responsive drug release from PFE-DOX-2 is achieved by the cleavage of acylhydrazone linkages in the acidic tumor intracellular microenvironment. Additionally, the drug release process can be monitored by the recovered fluorescence of conjugated polymers. Furthermore, the conjugated polymers can produce reactive oxygen species (ROS) under light irradiation after drug release in an acidic environment, which prevents possible phototoxicity to normal tissues. It is noted that PFE-DOX-2 demonstrates remarkable antitumor cell performance, which is attributed to its efficient cell uptake and powerful synergistic chemo-/PDT therapeutic effectiveness. This report thus provides a promising strategy for in vivo anticancer treatment with the construction of a stimuli-responsive multifunctional drug delivery system.

Stimuli-responsive nanocarrier delivery systems for Pt-based antitumor complexes: a review.

Platinum-based anticancer drugs play a crucial role in the clinical treatment of various cancers. However, the application of platinum-based drugs is heavily restricted by their severe toxicity and drug resistance/cross resistance. Various drug delivery systems have been developed to overcome these limitations of platinum-based chemotherapy. Stimuli-responsive nanocarrier drug delivery systems as one of the most promising strategies attract more attention. And huge progress in stimuli-responsive nanocarrier delivery systems of platinum-based drugs has been made. In these systems, a variety of triggers including endogenous and extracorporeal stimuli have been employed. Endogenous stimuli mainly include pH-, thermo-, enzyme- and redox-responsive nanocarriers. Extracorporeal stimuli include light-, magnetic field- and ultrasound responsive nanocarriers. In this review, we present the recent advances in stimuli-responsive drug delivery systems with different nanocarriers for improving the efficacy and reducing the side effects of platinum-based anticancer drugs.

3D printed and stimulus responsive drug delivery systems based on synthetic polyelectrolyte hydrogels manufactured via digital light processing.

Hydrogels are three-dimensional hydrophilic polymeric networks absorbing up to and even more than 90 wt% of water. These superabsorbent polymers retain their shape during the swelling process while enlarging their volume and mass. In addition to their swelling behavior, hydrogels can possess other interesting properties, such as biocompatibility, good rheological behavior, or even antimicrobial activity. This versatility qualifies hydrogels for many medical applications, especially drug delivery systems. As recently shown, polyelectrolyte-based hydrogels offer beneficial properties for long-term and stimulus-responsive applications. However, the fabrication of complex structures and shapes can be difficult to achieve with common polymerization methods. This obstacle can be overcome by the use of additive manufacturing. 3D printing technology is gaining more and more attention as a method of producing materials for biomedical applications and medical devices. Photopolymerizing 3D printing methods offer superior resolution and high control of the photopolymerization process, allowing the fabrication of complex and customizable designs while being less wasteful. In this work, novel synthetic hydrogels, consisting of [2-(acryloyloxy) ethyl]trimethylammonium chloride (AETMA) as an electrolyte monomer and poly(ethylene glycol)-diacrylate (PEGDA) as a crosslinker, 3D printed via Digital Light Processing (DLP) using a layer height of 100 μm, are reported. The hydrogels obtained showed a high swelling degree q∞m,t ∼ 12 (24 h in PBS; pH 7; 37 °C) and adjustable mechanical properties with high stretchability (εmax ∼ 300%). Additionally, we embedded the model drug acetylsalicylic acid (ASA) and investigated its stimulus-responsive drug release behaviour in different release media. The stimulus responsiveness of the hydrogels is mirrored in their release behavior and could be exploited in triggered as well as sequential release studies, demonstrating a clear ion exchange behavior. The received 3D-printed drug depots could also be printed in complex hollow geometry, exemplarily demonstrated via an individualized frontal neo-ostium implant prototype. Consequently, a drug-releasing, flexible, and swellable material was obtained, combining the best of both worlds: the properties of hydrogels and the ability to print complex shapes.

Amidation of methyl ester-functionalised poly(2-oxazoline)s as a powerful tool to create dual pH- and temperature-responsive polymers as potential drug delivery systems

We present the synthesis of different amine-functionalised poly(2-oxazoline)s, their dual pH and temperature response as well as their capability to as promising stimuli responsive drug delivery vectors.

Preparation and performance of a stimuli-responsive drug delivery system: novel light-triggered temperature-sensitive drug-loaded microcapsules.

Stimuli-responsive/smart drug delivery systems (DDSs), particularly those that use temperature as a stimuli-response factor to activate drug release, are the subject of recent research. A phase change material (PCM) is a popular thermally responsive material that can be used as a drug carrier and only when the system temperature is above the phase change point is the drug released following the phase change material changing from solid to liquid. In this study, a novel NIR light-triggered temperature-sensitive drug delivery system is developed for controllable release of acyclovir (ACV). For this purpose, a mixture of a phase change material (T38) and an ACV compound is first emulsified with copper oxide nanoparticles (CuO NPs) as a Pickering stabilizer and a photothermal conversion material, and then encapsulated with SiO2 to form a photothermal stimuli-responsive delivery system. This system shows a uniform spherical shape with a well-distinct core-shell structure, and is further experimentally proven to be able to controllably release drugs with solid-liquid transition of the phase change carrier upon temperature change. These results indicate that cumulative release of ACV can reach 51.2% at 40 °C within 20 hours, which is much higher than 27.3% release achieved below the melting point of T38. In addition, CuO NPs with excellent photothermal conversion ability endow the system with precisely controllable drug delivery via NIR light stimulation, where the cumulative drug release can reach 83.6% after 7 cycles of light stimulation, allowing controlled release at a specific time or location.

Multifunctional Oxidized Succinoglycan/Poly(N-isopropylacrylamide-co-acrylamide) Hydrogels for Drug Delivery

We prepared the self-healing and temperature/pH-responsive hydrogels using oxidized succinoglycan (OSG) and a poly (N-isopropyl acrylamide-co-acrylamide) [P(NIPAM-AM)] copolymer. OSG was synthesized by periodate oxidation of succinoglycan (SG) isolated directly from soil microorganisms, Sinorhizobium meliloti Rm1021. The OSG/P(NIPAM-AM) hydrogels were obtained by introducing OSG into P(NIPAM-AM) networks. The chemical structure and physical properties of these hydrogels were characterized by ATR-FTIR, XRD, TGA, and FE-SEM. The OSG/P(NIPAM-AM) hydrogels showed improved elasticity, increased thermal stability, new self-healing ability, and 4-fold enhanced tensile strength compared with the P(NIPAM-AM) hydrogels. Furthermore, the 5-FU-loaded OSG/P(NIPAM-AM) hydrogels exhibited effective temperature/pH-responsive drug release. Cytotoxicity experiments showed that the OSG/P(NIPAM-AM) hydrogels were non-toxic, suggesting that OSG/P(NIPAM-AM) hydrogels could have the potential for biomedical applications, such as stimuli-responsive drug delivery systems, wound healing, smart scaffolds, and tissue engineering.

Synthesis of Thermoresponsive, Catechol-Rich Poly(ethylene glycol) Brush Polymers for Attenuating Cellular Oxidative Stress.

Herein, we report a platform to integrate customizable quantities of catechol units into polymers by reacting caffeic acid carbonic anhydride with polymers having pendant amine groups. Brush poly(ethylene glycol)-caffeamide (PEG-CAF) copolymers based on oligo(ethylene glycol)methyl ether methacrylate (OEGMA500) were obtained with a catechol content of approximately 30, 40, and 50 mol % (vs OEGMA content). Owing to the hydrophobicity of the introduced CAF groups, the catechol copolymers exhibited cloud points in the range of 23-46 °C and were used to fabricate thermoresponsive FeIII metal-phenolic network capsules. Polymers with the highest CAF content (50 mol %) proved most effective for attenuating reactive oxygen species levels in vitro, in co-cultured fibroblasts, and breast cancer cells, even in the presence of an exogenous oxidant source. The reported approach to synthesize customizable catechol materials could be generalized to other amine-functional polymers, with potential biomedical applications such as adhesives or stimuli-responsive drug delivery systems.

Mesoporous silica gated mixed micelle for the targeted co-delivery of doxorubicin and paclitaxel

Breast cancer is the second most common cancer in women worldwide. A nano-drug delivery system (DDS) was fabricated by cooperating with two drug carriers (mesoporous silica nanoparticles and mixed micelles), providing a suitable method for designing stimuli-responsive drug delivery systems. The system is developed using paclitaxel (PTX) loaded mixed micelle as gating agents and doxorubicin (DOX) loaded mesoporous silica nanoparticles via Schiff base. Because of the pH-sensitive Schiff base, the gating micelles can achieve drug release under the acidic condition at pH = 5.5. In the present DDS, the Arginine-glycine-aspartic acid (RGD) peptide was utilized to target the specific cancer cell. The DDS shows 81.0% PTX and 65.0% DOX release after 72 h. The DDS was characterized well by FT-IR, UV-VIS, FE-SEM, BET, 1H NMR, and DLS. The newly formulated DDS was also examined by apoptosis to assess its pharmaceutical field application. The study results suggested that developed DDS serves as a potential device for targeted delivery and controlled release of DOX & PTX for cancer treatment.

Development of stimuli-responsive lyotropic liquid crystalline nanoparticles targeting lysosomes: Physicochemical, morphological and drug release studies

The abilities of sub-cellular targeting and stimuli-responsiveness are critical challenges in pharmaceutical nanotechnology. In the present study, glyceryl monooleate (GMO)-based non-lamellar lyotropic liquid crystalline nanoparticles were stabilized by the poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) block copolymer carrying tri-phenyl-phosphine cations (TPP-QPDMAEMA-b-PLMA), either used alone or in combination with other polymers as co-stabilizers. The systems were designed to perform simultaneously sub-cellular targeting, stimuli-responsiveness and to exhibit stealthiness. The physicochemical characteristics and fractal dimensions of the resultant nanosystems were obtained from light scattering techniques, while their micropolarity and microfluidity from fluorescence spectroscopy. Their morphology was assessed by cryo-TEM, while their thermal behavior by microcalorimetry and high-resolution ultrasound spectroscopy. The analyzed properties, including the responsiveness to pH and temperature, were found to be dependent on the combination of the polymeric stabilizers. The subcellular localization was monitored by confocal microscopy, revealing targeting to lysosomes. Subsequently, resveratrol was loaded into the nanosystems, the entrapment efficiency was investigated and in vitro release studies were carried out at different conditions, in which a stimuli-triggered drug release profile was achieved. In conclusion, the proposed multi-functional nanosystems can be considered as potentially stealth, stimuli-responsive drug delivery nanocarriers, with targeting ability to lysosomes and presenting a stimuli-triggered drug release profile.

A pH-responsive chiral mesoporous silica nanoparticles for delivery of doxorubicin in tumor-targeted therapy

The purpose of this study was to develop a nano-drug delivery system with intelligent stimuli-responsive drug delivery in tumor microenvironment (TME). Based on chiral mesoporous silica nanoparticles (CMSN) with a chiral recognition function in our previous research, a pH-responsive CMSN (CS-CMSN) was successfully prepared by chemical modification of chitosan (CS), and the related physicochemical properties, drug release performance, potential anti-tumor effect, and biological safety were studied. The results showed that the CS-CMSN were successfully modified by CS. Moreover, CS-CMSN displayed superior encapsulation ability for doxorubicin (DOX) and exhibited controllable pH-responsive drug release properties. In particular, in a physiological environment (pH 7.4/6.5), CS shielded the nanopores, prevented DOX release, and minimized side effects on normal cells. Once the CS-CMSN was exposed to the TME (pH 5.0), the pH-sensitive moiety of CS was cleaved in an acidic environment, along with the rapid release of DOX. In vitro cell experiments further proved that DOX@CS-CMSN was more strongly taken up by 4T1 cells and could enhance the toxicity to 4T1 tumor cells as well as promote cell apoptosis. More importantly, CS-CMSN were shown to have good biosafety in vitro and in vivo. Overall, the delivery of DOX by CS-CMSN nanocarriers is a promising strategy for tumor-targeted therapy.

Folate ‐ Conjugated Magnetite Nanoparticles for Targeted Drug Delivery and Hyperthermia Applications

AbstractResearch in magnetic nanoparticles mediated drug delivery system for cancer therapy is of current demand due to its various attributes. It provides a way for ease of stimuli responsive drug delivery and also act as a hyperthermic agent. Folic acid is extensively used for functionalisation of nanoparticles (NP) as various cancerous cells show overexpression of folate receptors. In this article, we report folic acid conjugated magnetite (Fe3O4) NP by two different ways and characterised by XRD, SEM, UV, FTIR and Raman spectroscopy. The folic acid was conjugated by its amine and carboxyl groups respectively on the magnetite NP to bestow them with targeting abilities. The NP formed are spherical and the size ranges from 32–100 nm and are highly aqueous dispersible as evidenced through the wettability studies. The blank NP shows some cytotoxicity on the MCF‐7 breast cancer cells probably due to oxidative stress. The NP shows high DOX loading efficiency due to higher surface area and negative surface charge. The superior magnetic properties of the NP assures hyperthermic temperature of 41 °C within 49 sec for 2 mg/ml NP concentration at an applied current of 273 A and frequency 316 kHz.

Ultrasound Responsive Smart Implantable Hydrogels for Targeted Delivery of Drugs: Reviewing Current Practices.

Over the last two decades, the process of delivering therapeutic drugs to a patient with a controlled release profile has been a significant focus of drug delivery research. Scientists have given tremendous attention to ultrasound-responsive hydrogels for several decades. These smart nanosystems are more applicable than other stimuli-responsive drug delivery vehicles (ie UV-, pH- and thermal-, responsive materials) because they enable more efficient targeted treatment via relatively non-invasive means. Ultrasound (US) is capable of safely transporting energy through opaque and complex media with minimal loss of energy. It is capable of being localized to smaller regions and coupled to systems operating at various time scales. However, the properties enabling the US to propagate effectively in materials also make it very difficult to transform acoustic energy into other forms that may be used. Recent research from a variety of domains has attempted to deal with this issue, proving that ultrasonic effects can be used to control chemical and physical systems with remarkable specificity. By obviating the need for multiple intravenous injections, implantable US responsive hydrogel systems can enhance the quality of life for patients who undergo treatment with a varied dosage regimen. Ideally, the ease of self-dosing in these systems would lead to increased patient compliance with a particular therapy as well. However, excessive literature has been reported based on implanted US responsive hydrogel in various fields, but there is no comprehensive review article showing the strategies to control drug delivery profile. So, this review was aimed at discussing the current strategies for controlling and targeting drug delivery profiles using implantable hydrogel systems.

Enzyme and Thermo Dual-stimuli Responsive DOX Carrier Based on PNIPAM Conjugated Mesoporous Silica.

Stimuli-responsive drug delivery systems have been proven to be a promising strategy to enhance tumor localization, overcome multidrug resistance (MDR), and reduce the side effects of chemotherapy agents. In this study, a temperature and redox dual stimuli-responsive system using mesoporous silica nanoparticles (MSNs) for targeted delivery of doxorubicin (DOX) was developed. Mesoporous silica nanoparticles were capped with poly(N-isopropylacrylamide) (PNIPAM), a thermo-sensitive polymer, with atom transfer radical polymerization (ATRP) method, via disulfide bonds (DOX-MSN-S-S-PNIPAM) to attain a controlled system that releases DOX under glutathione-rich (GSH-rich) environments and temperatures above PNIPAM's lower critical solution temperature (LCST). Morphological and physicochemical properties of the nanoparticles were indicated using transmission electron microscopy (TEM), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and Brunauer-Emmett-Teller (BET). The drug release tests were performed at 25°C and 41°C in the absence and presence of the DTT, and the obtained results confirmed the synergic effect of temperature and reductive agent on a dual responsive release profile with a 73% cumulative release at 41°C and reductive environment during 240 min. The average loaded drug content and encapsulation efficacy were reported as 42% and 29.5% at the drug: nanoparticle ratio of 1.5: 1. In vitro cytotoxicity assays on MCF-7 cell lines indicated significant viability decreased in cells exposed to DOX-MSN-S-S-PNIPAM compared to the free drug (DOX). Based on the results, DOX-MSN-S-S-PNIPAM has shown much more efficiency with stimuli-responsive properties in comparison to DOX on MCF-7 cancer cell lines.

Ultrasound-Induced Drug Release from Stimuli-Responsive Hydrogels.

Stimuli-responsive hydrogel drug delivery systems are designed to release a payload when prompted by an external stimulus. These platforms have become prominent in the field of drug delivery due to their ability to provide spatial and temporal control for drug release. Among the different external triggers that have been used, ultrasound possesses several advantages: it is non-invasive, has deep tissue penetration, and can safely transmit acoustic energy to a localized area. This review summarizes the current state of understanding about ultrasound-responsive hydrogels used for drug delivery. The mechanisms of inducing payload release and activation using ultrasound are examined, along with the latest innovative formulations and hydrogel design strategies. We also report on the most recent applications leveraging ultrasound activation for both cancer treatment and tissue engineering. Finally, the future perspectives offered by ultrasound-sensitive hydrogels are discussed.

Intelligent poly(l-histidine)-based nanovehicles for controlled drug delivery.

Stimuli-responsive drug delivery systems based on polymeric nanovehicles are among the most promising treatment regimens for malignant cancers. Such intelligent systems that release payloads in response to the physiological characteristics of tumor sites have several advantages over conventional drug carriers, offering, in particular, enhanced therapeutic effects and decreased toxicity. The tumor microenvironment (TME) is acidic, suggesting the potential of pH-responsive nanovehicles for enhancing treatment specificity and efficacy. The synthetic polypeptide poly(l-histidine) (PLH) is an appropriate candidate for the preparation of pH-responsive nanovehicles because the pKa of PLH (approximately 6.0) is close to the pH of the acidic TME. In addition, the pendent imidazole rings of PLH yield pH-dependent hydrophobic-to-hydrophilic phase transitions in the acidic TME, triggering the destabilization of nanovehicles and the subsequent release of encapsulated chemotherapeutic agents. Herein, we highlight the state-of-the-art design and construction of pH-responsive nanovehicles based on PLH and discuss the future challenges and perspectives of this fascinating biomaterial for targeted cancer treatment and "benchtop-to-clinic" translation.

Current Advances in Nano-Based and Polymeric Stimuli-Responsive Drug Delivery Targeting the Ocular Microenvironment: A Review and Envisaged Future Perspectives.

Optimal vision remains one of the most essential elements of the sensory system continuously threatened by many ocular pathologies. Various pharmacological agents possess the potential to effectively treat these ophthalmic conditions; however, the use and efficacy of conventional ophthalmic formulations is hindered by ocular anatomical barriers. Recent novel designs of ophthalmic drug delivery systems (DDS) using nanotechnology show promising prospects, and ophthalmic formulations based on nanotechnology are currently being investigated due to their potential to bypass these barriers to ensure successful ocular drug delivery. More recently, stimuli-responsive nano drug carriers have gained more attention based on their great potential to effectively treat and alleviate many ocular diseases. The attraction is based on their biocompatibility and biodegradability, unique secondary conformations, varying functionalities, and, especially, the stimuli-enhanced therapeutic efficacy and reduced side effects. This review introduces the design and fabrication of stimuli-responsive nano drug carriers, including those that are responsive to endogenous stimuli, viz., pH, reduction, reactive oxygen species, adenosine triphosphate, and enzymes or exogenous stimuli such as light, magnetic field or temperature, which are biologically related or applicable in clinical settings. Furthermore, the paper discusses the applications and prospects of these stimuli-responsive nano drug carriers that are capable of overcoming the biological barriers of ocular disease alleviation and/or treatment for in vivo administration. There remains a great need to accelerate the development of stimuli-responsive nano drug carriers for clinical transition and applications in the treatment of ocular diseases and possible extrapolation to other topical applications such as ungual or otic drug delivery.

Injectable magnetic montmorillonite colloidal gel for the postoperative treatment of hepatocellular carcinoma

Bioactive materials have been extensively developed for the adjuvant therapy of cancer. However, few materials can meet the requirements for the postoperative resection of hepatocellular carcinoma (HCC) due to massive bleeding and high recurrence. In particular, combination therapy for HCC has been highly recommended in clinical practice, including surgical resection, interventional therapy, ablation therapy and chemotherapy. Herein, an injectable magnetic colloidal gel (MCG) was developed by controllable electrostatic attraction between clinically available magnetic montmorillonites and amphoteric gelatin nanoparticles. The optimized MCG exhibited an effective magnetic heating effect, remarkable rheological properties, and high gel network stability, realizing the synergistic treatment of postoperative HCC by stimuli-responsive drug delivery, hemostasis and magnetic hyperthermia. Furthermore, a minimal invasive MCG-induced interventional magnetic hyperthermia therapy (MHT) under ultrasound guidance was realized on hepatic tumor rabbits, providing an alternative therapeutics to treat the postoperative recurrence. Overall, MCG is a clinically available injectable formulation for adjuvant therapy after HCC surgical resection.