Responsive Drug Delivery System Research Articles

Simultaneous surface functionalization and drug loading: A novel method for fabrication of cellulose nanocrystals-based pH responsive drug delivery system

Herein, a novel strategy for surface functionalization and drug loading of cellulose nanocrystals (CNCs) through formation of hydrazone bonds between functionalized CNCs and aldehyde group containing polyethylene glycol (CHO-PEG)/anticancer drug doxorubicin (DOX) was reported for the first time. DOX could be loaded on PEGylated CNCs with high capacity and released from drug complexes (P-CNCs-D) with pH dependent behavior. The biological evaluation results demonstrated that drug carriers (CNCs-EBO-NH) showed negative cytotoxicity while DOX could be transported into cells and exhibits desirable anticancer effects. As compared with other method, the method developed in this work is rather simple and effective and can be achieved for simultaneous for surface functionalization and drug loading in a one-pot route. This work will open a new avenue for fabrication of various multifunctional composites based on other carbohydrate polymers or materials and to explore their applications in biomedical fields.

ROS-responsive liposomes with NIR light-triggered doxorubicin release for combinatorial therapy of breast cancer

BackgroundReactive oxygen species (ROS)-responsive drug delivery systems (DDSs) are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve spatially and temporally controllable and accurate drug release in tumor sites based on ROS-responsive DDSs. To solve this problem, we designed a nanosystem combined photodynamic therapy (PDT) and ROS-responsive chemotherapy.MethodsIndocyanine green (ICG), an ROS trigger and photosensitizer, and pB-DOX, a ROS-responsive prodrug of doxorubicin (DOX), were coencapsulated in polyethylene glycol modified liposomes (Lipo/pB-DOX/ICG) to construct a combination therapy nanosystem. The safety of nanosystem was assessed on normal HEK-293 cells, and the cellular uptake, intracellular ROS production capacity, target cell toxicity, and combined treatment effect were estimated on human breast cancer cells MDA-MB-231. In vivo biodistribution, biosafety assessment, and combination therapy effects were investigated based on MDA-MB-231 subcutaneous tumor model.ResultsCompared with DOX·HCl, Lipo/pB-DOX/ICG showed higher safety on normal cells. The toxicity of target cells of Lipo/pB-DOX/ICG was much higher than that of DOX·HCl, Lipo/pB-DOX, and Lipo/ICG. After endocytosis by MDA-MB-231 cells, Lipo/pB-DOX/ICG produced a large amount of ROS for PDT by laser irradiation, and pB-DOX was converted to DOX by ROS for chemotherapy. The cell inhibition rate of combination therapy reached up to 93.5 %. After the tail vein injection (DOX equivalent of 3.0 mg/kg, ICG of 3.5 mg/kg) in mice bearing MDA-MB-231 tumors, Lipo/pB-DOX/ICG continuously accumulated at the tumor site and reached the peak at 24 h post injection. Under irradiation at this time point, the tumors in Lipo/pB-DOX/ICG group almost disappeared with 94.9 % tumor growth inhibition, while those in the control groups were only partially inhibited. Negligible cardiotoxicity and no treatment-induced side effects were observed.ConclusionsLipo/pB-DOX/ICG is a novel tool for on-demand drug release at tumor site and also a promising candidate for controllable and accurate combinatorial tumor therapy.

Synthesis of temperature/pH dual-responsive mesoporous silica nanoparticles by surface modification and radical polymerization for anti-cancer drug delivery

In this study, mesoporous silica nanoparticles were synthesized from rice husk (RMSN-D) as a natural, available, economical, and non-toxic source for cancer treatment. Also, to increase the drug delivery efficiency, after modifying the surface of nanoparticles by vinyl groups (RMSN-DV), acrylic acid and n-isopropyl acrylamide were polymerized on the RMSN-DV surface by a well-tuned monomer ratio to create a biocompatible smart dual responsive drug delivery system (RMSN-DAN). The structure and physicochemical properties of the nanoparticles were characterized by XRD, FT-IR, SEM, TEM, EDS, BET, HNMR, and EDS techniques. The results indicated that monomers were successfully grafted onto the RMSN-D. Doxorubicin (Dox) was exploited as a model drug, and in-vitro Dox release was investigated. The result exhibited an excellent temperature and pH-responsive controlled release behavior. The biocompatibility and safety of natural silica source and RMSN-DAN were demonstrated Via MTT assay. Dox-loaded RMSN-DAN demonstrated cytotoxic activity similar to free Dox to MCF-7 cell line. Moreover, apoptosis of the MCF-7 cell line was investigated by flow cytometric analysis and morphological study. Therefore, this dual-responsive biocompatible and economic RMSN-DAN nanocarrier could be applied in targeting and stimuli-responsive drug delivery due to negligible drug leakage during blood circulation whilst having a rapid release upon reaching tumor tissues.

GRGDS-conjugated and curcumin-loaded magnetic polymeric nanoparticles for the hyperthermia treatment of glioblastoma cells

Thermally responsive and ligand-mediated drug delivery systems have the potential to improve the treatment of brain tumors, especially, most lethal one, glioblastoma multiform (GBM). Magnetic nanoparticle-mediated hyperthermia becomes one of the most promising alternative therapy for GBM treatment in cases where localized heating and targeted delivery of a therapeutic drug can be achieved on the tumor site. In this study, it is aimed to increase the therapeutic efficiency of multi-functionalized nanoparticles (NPs) in combination with radiofrequency hyperthermia (RF-HT) on GBM cells. For this purpose, firstly, a low-cost and portable home-built RF-HT system suitable for in vitro/in vivo studies was successfully implemented and tested at 13.56 MHz frequency with power up to approximately 400 W. Subsequently, the highly monodispersed superparamagnetic iron oxide nanoparticles (SPIONs), which could interact with the RF magnetic field, were synthesized with the mean particle size of 5.6 ± 0.9 nm. The obtained SPIONs were coated with poly (lactic-co-glycolic acid)-poly (ethylene glycol) di-block copolymer (PLGA-b-PEG). Most of the SPIONs were uniformly distributed in such a well-defined spherical-shaped polymeric NP. Moreover, curcumin (Cur), a potential agent for GBM treatment, was loaded into the magnetic polymeric nanoparticles (m-PNPs) with a loading capacity of 8% (w/w, Cur/NPs) and a mean diameter of Cur-loaded m-PNPs (Cur-m-PNPs) was 142 ± 70 nm. To increase cellular uptake and targeting ability of NPs, glycine-arginine-glycine-aspartic acid-serine (GRGDS) peptide was immobilized on the Cur-m-PNPs and the amount of GRGDS was detected as 37 µg/mg NPs. In vitro cytotoxicity studies revealed that the presence of GRGDS on Cur-m-PNPs (GRGDS-Cur-m-PNPs) improved the cytotoxic efficiency of Cur-m-PNPs by 6-fold in GBM cells for all incubation times (24, 48 and 72 h). Furthermore, NPs with RF treatment exhibited higher antitumor activity than that of NPs without RF on GBM cells. This result may be attributed to the thermal (SPIONs) or non-thermal (cellular membrane) effects or both of them on cells. Overall, this study showed that RF-HT in combination with GRGDS-Cur-m-PNPs could provide a feasible approach to improve GBM treatment.

Construction of Polymeric Micelles for Improving Cancer Chemotherapy by Promoting the Production of Intracellular Reactive Oxygen Species and Self‐Accelerating Drug Release

AbstractLots of efforts have been devoted to enhancing the antitumor efficacy of reactive oxygen species (ROS)‐responsive nanoscale drug delivery systems. Here, a ROS‐responsive amphiphilic polymer (mPEG‐b‐poly(thioacetal‐thioether), P2) with property of generation and self‐sustained high level of ROS, and a control material mPEG‐b‐poly(ester‐thioether) (P1) were constructed and characterized by proton nuclear magnetic resonance (1H NMR). The two polymers could self‐assemble into micelles and the doxorubicin loading content of P1 and P2 micelles were 13.08 % and 13.51 %, respectively. The two polymers could self‐assemble into micelles and exhibit good DOX loading capacity. ROS‐responsiveness of P1 and P2 micelles was investigated by1H NMR, dynamic light scattering (DLS), and scanning electron microscope (SEM). The results of in vitro ROS detection indicated that P2 micelles could ROS‐responsive release of cinnamaldehyde, and promote intracellular generation of ROS and maintain high level of ROS. DOX/P1 micelle shown comparable in vitro antitumor efficacy with DOX/P2 micelle, and a slightly lower IC50 value was due to DOX/P1 micelle has faster cell internalization, poorer micelle stability and integrality. Considering the stability of the nanoparticle circulation in vivo, the DOX/P2 micelle containing both thioether and thioacetal would be more suitable and could show better in vivo antitumor efficacy.

Inflammatory tumor microenvironment responsive neutrophil exosomes-based drug delivery system for targeted glioma therapy

Clinical treatment of malignant glioma remains a major challenge due to high infiltrative growth and chemotherapeutic resistance of tumors and the presence of the blood brain barrier (BBB). Advanced nanoplatforms that can efficiently cross the BBB and target to brain tumor are urgently needed. Encouraged by the intrinsic inflammatory chemotaxis and excellent BBB-crossing capability of neutrophils, a bioinspired neutrophil-exosomes (NEs-Exos) system for delivering loaded doxorubicin (DOX) drug for glioma treatment is proposed and systematically investigated. In vivo zebrafish and C6-Luc glioma-bearing mice models show that NEs-Exos carrying the drug rapidly penetrate the BBB and migrate into the brain. Additionally, a transwell BBB model and mouse brain inflammatory study show that NEs-Exos can respond chemotactically to inflammatory stimuli and target infiltrating tumor cells in inflamed brain tumors. Moreover, intravenous injection of NEs-Exos/DOX efficiently suppress tumor growth and prolong survival time in a glioma mouse model. On the basis of these results, NEs-Exos are confirmed to have neutrophil-like chemotactic function and BBB penetration. This novel NEs-Exos/DOX delivery platform represents a promising chemotherapeutic approach for clinical treatment of glioma and other solid tumor or brain diseases.

Multi-stimuli responsive hollow MnO2-based drug delivery system for magnetic resonance imaging and combined chemo-chemodynamic cancer therapy

The exploration and application of hollow manganese dioxide nanoparticle (HMDN) for biosensing and biomedicine has gained significant research attention in the past decade. In this study, a type of biodegradable HMDN is prepared for multi-stimuli responsive tumor-targeted drug delivery, which was successfully loaded with doxorubicin hydrochloride (DOX). Then, the drug-loaded HMDN is functionalized with polyethyleneimine (PEI) as a gatekeeper followed by citraconic anhydride (cit) functionalized poly-L-lysine (PLL(cit)) as a charge reversal moiety successively to yield the resultant DOX@HMDN-PEI-PLL(cit) nanoparticles. In vitro study showed that DOX@HMDN-PEI-PLL(cit) exhibited a ‘‘stealthy’’ property under physiological conditions and enhanced cellular uptake activity in response to the mild acidic tumor microenvironment due to the departure of cit. In vitro release profiles proved that the decomposition of HMDN to Mn2+ under acidic condition/high glutathione (GSH) concentration triggered the release of DOX and Fenton-like reaction for improved therapeutic effect. And Mn2+ could also act as a T1-weighted magnetic resonance imaging (MRI) contrast agent. In vivo studies further proved with both the charge reversal and combined therapy properties, DOX@HMDN-PEI-PLL(cit) showed a good tumor enrichment ability and therapeutic effect with few side effects to the mice. These results demonstrate that DOX@HMDN-PEI-PLL(cit) nanoparticles are promising drug delivery systems for targeted cancer therapy. Statement of significanceTraditional chemotherapy based on anticancer drugs such as doxorubicin hydrochloride (DOX) shows limited efficacy with serious side effects. We employed hollow manganese dioxide nanoparticle (HMDN) to loaded DOX and coated it with polyethyleneimine and then citraconic anhydride functionalized poly-L-lysine to endow it with a charge reversal property to obtain a multi-stimuli responsive drug delivery system named DOX@HMDN-PEI-PLL(cit). It was ‘‘stealthy’’ with low cellular uptake capability by normal cells, but could be “acid-activated” in tumors for endocytosis by cancer cells to reduce side effects. HMDN could be decomposed to Mn2+ under acidic conditions/high glutathione concentration to release DOX intracellular. DOX and Mn2+ catalyzed Fenton-like reaction could achieve a combined chemo-chemodynamic therapy. And Mn2+ could be used for T1-weighted magnetic resonance imaging.

Novel pH-responsive nanohybrid for simultaneous delivery of doxorubicin and paclitaxel: an in-silico insight

BackgroundThe distribution of drugs could not be controlled in the conventional delivery systems. This has led to the developing of a specific nanoparticle-based delivery system, called smart drug delivery systems. In cancer therapy, innovative biocompatible nanocarriers have received much attention for various ranges of anti-cancer drugs. In this work, the effect of an interesting and novel copolymer named "dimethyl acrylamide-trimethyl chitosan" was investigated on delivery of paclitaxel and doxorubicin applying carboxylated fullerene nanohybrid. The current study was run via molecular dynamics simulation and quantum calculations based on the acidic pH differences between cancerous microenvironment and normal tissues. Furthermore, hydrogen bonds, radius of gyration, and nanoparticle interaction energies were studied here. Stimulatingly, a simultaneous pH and temperature-responsive system were proposed for paclitaxel and doxorubicin for a co-polymer. A pH-responsive and thermal responsive copolymer were utilized based on trimethyl chitosan and dimethyl acrylamide, respectively. In such a dualistic approach, co-polymer makes an excellent system to possess two simultaneous properties in one bio-polymer.ResultsThe simulation results proposed dramatic and indisputable effects of the copolymer in the release of drugs in cancerous tissues, as well as increased biocompatibility and drug uptake in healthy tissues. Repeated simulations of a similar article performed for the validation test. The results are very close to those of the reference paper.ConclusionsOverall, conjugated modified fullerene and dimethyl acrylamide-trimethyl chitosan (DMAA-TMC) as nanohybrid can be an appropriate proposition for drug loading, drug delivery, and drug release on dual responsive smart drug delivery system.

Reactive oxygen species and glutathione dual responsive nanoparticles for enhanced prostate cancer therapy

Docetaxel (DTX)-based chemotherapy of prostate cancer is still confronted with significant challenges due to insufficient drug accumulation at the tumor sites and the systemic side effects on normal cells and organs. Tumor microenvironment-responsive nanosized drug delivery systems have shown enormous potential to improve the anticancer efficacy and minimize the systemic side effects of chemotherapeutics. However, most of the currently redox-responsive nanoparticles respond only to single stimuli, which compromise the treatment effect. Hence, inspired by the abundance of reactive oxygen species (ROS) and intracellular glutathione (GSH) in cancer cells, we proposed a unique ROS and GSH dual responsive nanocarrier (PCL-SS) for DTX delivery. The DTX-loaded PCL-SS nanoparticles (PCL-SS@DTX NPs) were not only stable in a normal physiological environment but also rapidly triggered DTX release in prostate cancer cells. In vitro experiments showed that PCL-SS@DTX NPs had robust prostate cancer cell cytotoxicity, induced cell apoptosis, inhibited cell migration and invasion and exhibited satisfactory biocompatibility. In mice bearing orthotopic prostate cancer, PCL-SS@DTX NPs could accumulate in orthotopic tumor sites and then significantly weaken tumor growth by inhibiting prostate cancer cell proliferation and inducing cell apoptosis, without obvious damages to major organs. Overall, this dual responsive nanosized drug delivery system may act as a promising therapeutic option for prostate cancer chemotherapy.

Endogenous Enzyme-responsive Nanoplatforms for Anti-tumor Therapy.

The emergency of responsive drug delivery systems has contributed to reduced cytotoxicity, improved permeability in tissues and extended circulation time of the active drug. In particular, enzyme-responsive nanoplatforms have attracted a lot of attention due to the specificity and efficiency of an enzyme-catalyzed reaction. In this review, enzyme-based mono responsive drug delivery systems designed in the past 5 years have been summarized. These drug delivery systems were introduced by different tumor-related enzymes such as matrix metalloproteinase, esterase, hyaluronidase, caspase and cathepsin. Moreover, the enzyme-sensitive nanoplatforms activated by dual-stimuli have been also described. Although great progress had been made in the past years, the translation into clinical practice is still difficult. Thus, three obstacles (enzyme heterogeneity, reaction environment, animal model) were also discussed. In short, enzyme-activated drug delivery systems offer great potential in treating cancers.

A novel multifunctional NCQDs-based injectable self-crosslinking and in situ forming hydrogel as an innovative stimuli responsive smart drug delivery system for cancer therapy

In this work, we offer an easy approach to develop a novel injectable, pH sensitive and in situ smart drug delivery system for use in cancer treatments. The developed hydrogels containing nitrogen doped carbon quantum dots (NCQD), doxorubicin (Dox) and hydroxyapatite (HA) were obtained by in situ self-crosslinking. Characterization of the synthesized nanomaterials, interactions between NCQD/Dox/HA hydrogel structure were carried out by TEM, FESEM, EDS, FTIR, XPS, XRD, Zeta potential, DLS, UV–Vis, SEM, gelation time, injectability and DIST measurements. In addition, antibacterial evaluation which was performed against Staphylococcus aureus realized that HA compound significantly increased the antibacterial activity of the hybrid hydrogel. The anticancer drug release to the tumor cell microenvironment with a pH of 5.5 was found to be higher compared to the release in the normal physiological range of pH 6.5 and 7.4. MTT and live/dead assays were also performed using L929 fibroblastic cell lines to investigate the cytotoxic behavior of NCQDs, and NCQDs/Dox/HA hydrogels. Furthermore, the NCQDs/Dox/HA hydrogel could transport Dox within a MCF-7 cancerous cell at specifically acidic pH. Additionally, imaging of cell line was observed using NCQDs and their use in imaging applications and multicolor features in the living cell system were evaluated. The overall study showed that in situ formed NCQDs/Dox/HA hydrogel represented a novel and multifunctional smart injectable controlled-release drug delivery system with great potential, which may be considered as an attractive minimal invasive smart material for future intelligent delivery of chemotherapeutic drug and disease therapy applications.

Ultrasound responsive erythrocyte membrane-derived hybrid nanovesicles with controlled drug release for tumor therapy.

An ultrasound responsive erythrocyte membrane-derived hybrid nanovesicle drug delivery system (DOX/HMME@FA-NL) is constructed by the membrane fusion functionalization strategy for controlled drug release and enhanced tumor therapy. The reliability and effectiveness of the membrane fusion strategy are confirmed through characterization of the particle size and zeta potential, Förster energy resonance transfer and fluorescence co-localization analyses. The DOX/HMME@FA-NL could be triggered for reactive oxygen species (ROS) generation under ultrasound stimulation. And the unsaturated phospholipids in DOX/HMME@FA-NL can be oxidized by ROS, leading to the destruction of the structure of the hybrid membrane to achieve the controlled release of drugs, thereby enhancing their tumor cell killing effect. Besides, the linkage of the folate targeting group also enhances the tumor targeting ability of DOX/HMME@FA-NL. H22 tumor-bearing mice were intravenously injected with DOX/HMME@FA-NL and treated with ultrasound, they achieved better than expected tumor sonodynamic response treatment effects.

PH and redox triggered doxorubicin release from covalently linked carbon dots conjugates.

Tumor microenvironment responsive drug delivery systems are potential approaches to reduce the acute toxicity caused by high-dose cancer chemotherapy. Notwithstanding the conventional nano-drug delivery systems, the redox and pH stimuli drug delivery systems are currently gaining attention. Therefore, the current study was designed to compare three different covalent carbon dots (C-dots) systems based on doxorubicin (dox) release profiles and cancer cell viability efficacy under acidic and physiological conditions. The C-dots nanosystems that were examined in this study are directly conjugated (C-dots-dox), pH triggered (C-dots-HBA-dox), and the redox stimuli (C-dots-S-S-dox) conjugates. The drug loading content (DLC%) of the C-dots-S-S-dox, C-dots-HBA-dox, and C-dots-dox was 34.2 ± 0.4, 60.0 ± 0.3, and 70.0 ± 0.2%, respectively, that examined by UV-vis spectral analysis. The dox release paradigms were emphasized that all three conjugates were promisingly released the dox from C-dots faster in acidic pH than in physiological pH. The displayed highest dox released percentage in the acidic medium was 74.6 ± 0.8% obtained by the pH stimuli, C-dots-HBA-dox conjugate. When introducing the redox inducer, dithiothreitol (DTT), preferentially, the redox stimuli C-dot-S-S-dox conjugate demonstrated a faster dox release at acidic pH than in the pH 7.4. The SJGBM2 cell viability experiments revealed that the pH stimuli, C-dots-HBA-dox conjugate, displayed a significant cell viability drop in the artificially acidified pH 6.4 medium. However, in the physiological pH, the redox stimuli, C-dots-S-S-dox conjugate, was promising over the pH stimuli C-dots-HBA-dox, exhibiting cell viability of 60%, though its' efficacy dropped slightly in the artificially acidified pH 6.4 medium. Moreover, the current study illustrates the stimuli conjugates' remarkable efficacy on sustain drug release than direct amide linkage.

Nanoparticle-based therapeutics of inflammatory bowel diseases: a narrative review of the current state and prospects

Abstract Inflammatory bowel disease (IBD), such as Crohn disease and ulcerative colitis, are chronic relapsing disorders of the gastrointestinal tract. Characterized pathologically by intestinal inflammation and epithelial injury, great challenges exist for the treatment of IBD due to its complicated etiology and incurable nature. Traditional strategies rely on frequent and long-term administration of high dosages of anti-inflammatory drugs, which inevitably cause side effects. Therefore, novel therapeutic methods and drug delivery systems capable of improving therapeutic effect while simultaneously decreasing side effects need to be developed. The emergence of nanotechnology provides alternative approaches for diagnosis and treatment of IBD, as nanoparticles (NPs) have unique physicochemical properties such as targeting to the site of inflammation and the ability to alter the pharmacokinetics of traditional drugs. This review first introduces the pathophysiological features and microenvironment of IBD, and then summarizes different strategies and mechanisms of NP-based colon-targeted drug delivery systems, including size-dependent, multi-stimuli responsive, active targeting, intestinal microbiota-related, and novel natural-derived NP-mediated drug delivery systems. We also discuss applications of nanozymes and NP-based imaging in diagnostics and treatment of IBD. Finally, challenges and prospects in the field are proposed to promote the development of targeted drug delivery for IBD treatment.

Controllable Growth and Assembling Strategies Based on Nanomaterials for Targeted and Precise Therapy of Malignant Cancers

What is the most favorite and original chemistry developed in your research group??The sensitive detection methods and specific bioimaging strategies for tumor biomarkers, as well as the diagnosis‐therapy integration strategies of malignant cancers.How do you get into this specific field? Could you please share some experiences with our readers?I have entered this field for more than 10 years. Till now, cancer remains a major human health problem. Thus, the research about cancer diagnosis and therapy is quite important and interesting. Therefore, our group transferred our research attentions to this field.How do you supervise your students?In our group, we try our best to give every student the chance to demonstrate his talents and abilities. They could freely express their ideas or questions in our weekly seminar. Also I encourage the students to review the updated literature and have a clear understanding of the work they did.What is the most important personality for scientific research?I think the creativity and dedication to the research are very important for the scientific research.What's your hobbies? What's your favorite book(s)?Swimming and walking are my hobbies. I like to read some history books.How do you keep balance between research and family?A successful researcher should keep good balance between research and family. Usually, I try to elevate my work efficiency to finish all the work during the working time. Then, I have full time to be with my family.Who influences you mostly in your life?My doctoral adviser, professor Hongyuan Chen.What is your favorite journal(s)?Chemical Society Reviews and Journal of the American Chemical Society.Could you please give us some advices on improving Chinese Journal of Chemistry?Encourage the innovative submissions and endow the editor‐in‐chief with larger discretion.In the past decades, nanomaterials have achieved great development and received wide application in various fields. Nanomaterials‐based cancer therapy strategies brought great prospects and chance. Recently, we have developed controllable growth and assembling strategies based on nanomaterials for chemotherapy, photodynamic therapy, photothermal therapy and gene therapy. For chemotherapy, we modified DNA or RNA‐based nanostructures including DNA network, DNA sphere and RNA nanoflowers on the surface of magnetic nanoparticles (MNPs), gold nanoparticles (AuNPs) and mesoporous silica nanoparticles (MSPs) to develop feasible drug delivery systems, which could achieve the targeted therapy and controllable release. Especially, we developed telomerase‐ responsive drug delivery systems to achieve the highly‐localized chemotherapy. Furthermore, we established novel photodynamic nanotheranostic agents based on upconversion nanoparticles (UCNPs), which owned enhanced energy transfer efficiencies and improved production amount of reactive oxygen species (ROSs). For the photothermal therapy, we investigated novel composite nanomaterials to increase the ability of light‐to‐heat conversion. Finally, we also investigated the application of the RNA‐involved hydrogel in gene therapy. These developed strategies proved the great potential and application of nanomaterials in cancer therapy.

RETRACTED: Synthesis of hollow maghemite (-Fe2O3) particles for magnetic field and pH-responsive drug delivery and lung cancer treatment

Abstract The development of smart stimuli-responsive materials for drug delivery offers new opportunities for precise drug release and cancer chemotherapy. A combination of more than one stimuli is highly desirable to further maximize the therapy by taking the advantages of various unique merits. Herein, we employed polyethylene glycol (PEG) functionalized γ-Fe2O3 particles (γ-Fe2O3/PEG) as a novel magnetic drug carrier for doxorubicin (DOX) delivery. The results showed that the γ-Fe2O3/PEG exhibited excellent thermal effects under alternating magnetic field (AMF), high magneto-thermal stability, and large DOX loading capacity. Furthermore, the effects of pH and AMF on the DOX drug release were studied. It was discovered that DOX loaded γ-Fe2O3/PEG carriers were highly responsive to both AMF and pH, resulting in significantly improved cancer cell killing capability over a single stimulus. The magnetic and pH responsive drug delivery system provided a new opportunity to minimize the side effects and maximize the therapeutic efficiency of lung cancer treatment.

Aptamer-functionalized molybdenum disulfide nanosheets for tumor cell targeting and lysosomal acidic environment/NIR laser responsive drug delivery to realize synergetic chemo-photothermal therapeutic effects.

Molybdenum disulfide (MoS2), one representative 2D nanomaterial, has recently emerged as a unique platform in the biomedical field. However, its application in drug delivery systems should be further exploited. Here, we report a novel tumor cell targeting and lysosomal acidic environment/NIR laser dual responsive drug delivery system for synergetic chemo-photothermal treatment of cancer cells. The MoS2 nanosheets were loaded with chemotherapy drug doxorubicin (DOX) and coated with polydopamine (PDA) layer. Then, thiolated aptamer AS1411 and polyethylene glycol (PEG) were modified onto MoS2 nanosheets through Michael addition reaction to construct DOX@Apt-PEG-PDA-MoS2 nanosheets. The aptamer modification endowed the nanoplatform with targeting ability to breast cancer MCF-7 cells. MoS2 and PDA converted 808nm NIR laser into heat and played the role of photothermal therapy (PTT). Tumor lysosomal acidic environment and NIR laser irradiation accelerated the release of DOX from the nanosheets. The nanocarrier Apt-PEG-PDA-MoS2 showed good biocompatibility, and DOX@Apt-PEG-PDA-MoS2 showed synergetic chemo-photothermal therapy effects with significantly enhanced anti-tumor efficacy, suggesting that this MoS2-based drug delivery platform is promising for targeted and synergetic treatment of cancer.

Ultrasound and Magnetic Responsive Drug Delivery Systems for Cardiovascular Application

With the increasing insight into molecular mechanisms of cardiovascular disease, a promising solution involves directly delivering genes, cells, and chemicals to the infarcted myocardium or impaired endothelium. However, the limited delivery efficiency after administration fails to reach the therapeutic dose and the adverse off-target effect even causes serious safety concerns. Controlled drug release via external stimuli seems to be a promising method to overcome the drawbacks of conventional drug delivery systems (DDSs). Microbubbles and magnetic nanoparticles responding to ultrasound and magnetic fields respectively have been developed as an important component of novel DDSs. In particular, several attempts have also been made for the design and fabrication of dual-responsive DDS. This review presents the recent advances in the ultrasound and magnetic fields responsive DDSs in cardiovascular application, followed by their current problems and future reformation.

Progress of Stimuli-Responsive Nanoscale Metal Organic Frameworks as Controlled Drug Delivery Systems.

Development of controlled drug delivery systems can improve the pharmacokinetic characteristics of drug molecules in the human body, thereby significantly improving the utilization rate of drugs and reducing toxicity and side effects caused by their high concentrations, which can occur when delivery is not controlled. Metal organic frameworks are a new class of very promising crystalline microporous materials, especially when the size is reduced to the nanometer range. Metal-organic frameworks exhibit large specific surface areas, tunable compositions, and easy functionalization. In recent years, an increasing number of studies have reported the remarkable advances in multifunctional nanoscale metal-organic frameworks in drug delivery. To review the latest research involving advances in stimuli-responsive nanoscale metal organic frameworks as drug delivery systems in controlled-release drugs. We first introduce the two main strategies associated with nanoscale metal organic frameworks used in drug loading: direct assembly and post-encapsulation. We next focus on the latest discoveries of nanoscale metal-organic framework-based stimulus response systems for drug delivery, including pH, magnetics, light, ion, temperature, and other stimuli, as well as multiple stimulus- responsive drug delivery systems. Finally, we discuss the challenges and future developmental directions of nanoscale metal-organic framework-based controlled drug release.

Nanomedicine and chemotherapeutics drug delivery: challenges and opportunities

Cancer is considered as one of the biggest threats to humans worldwide. Researchers suggest that tumour is not just a single mass, it comprises cancerous cells surrounded by noncancerous cells such as immune cells, adipocytes and cancer stem cells (CSCs) in the extracellular matrix (ECM) containing distinct components such as proteins, glycoproteins and enzymes; thus tumour microenvironment (TME) is partially complex. Multiple interactions happen in the dynamic microenvironment (ME) lead to an acidic, hypoxic and stiff ME that is considered as one of the major contributors to cancer progression and metastasis. Furthermore, TME involves in drug resistance mechanisms and affects enhanced permeability and retention (EPR) in tumours. In such a scenario, the first step to accomplish satisfying results is the identification and recognition of this ME. Then designing proper drug delivery systems can perform selectively towards cancerous cells. In this way, several targeting and stimuli/enzyme responsive drug delivery systems have been designed. More importantly, it is necessary to design a drug delivery system that can penetrate deeper into the tumours, efficiently and selectively. Various drug delivery systems such as exosomes and size-switchable nanocarriers (NCs) could decrease side effects and increase tumour treatment results by selective accumulation in tumours. In this review, TME features, current drug delivery approaches, challenges and promising strategies towards cancer treatment are discussed.