Stimuli-responsive Release Research Articles

DIFFERENT TYPES OF NANOCARRIERS FOR TARGETED TREATMENT OF HIV/AIDS

AIDS is a major challenge in the 21st century. AIDS, stands for Acquired Immune Deficiency Syndrome, is a serious health problem and a fast-spreading incurable disease. It is a disorder of the cell-mediated immune system of the body. It is localized in certain inaccessible compartment of the body such as the CNS, lymphatic system and in the macrophages, where it cannot be reached by the majority of the therapeutic agent in adequate concentration or in which the therapeutic agents cannot for the necessary duration. HIV/AIDS infection are reducing incidence with the advent of Highly Active Antiretroviral Therapy (HAART). There remain a number of challenges including drug resistance, anatomical barriers to antiretroviral therapy. To overcome these different nanocarriers with the stimuli-responsive release are proposed for antiretroviral agents. Nanocarrier and those optimized for cancer chemotherapy. These include the development nanoparticles capable of passive and active targeting as well as those that are responsive to various internal and externl triggers. Nanocarriers can also provide many of the advantages of lipid system. Liposome, solid lipid nanoparticle, nanoemulsion, dendrimers, polymeric nanoparticle are the example of drug delivery systems that are under investigation for the treatment of HIV/AIDS. This review aims to summarize the ability of nanocarrier technology to provide a rational approach for anti-HIV therapy.

Enhancing corrosion protection properties of sol-gel coating by pH-responsive amino-silane functionalized graphene oxide-mesoporous silica nanosheets

Amino-silane functionalized graphene oxide-ordered mesoporous silica nanocontainer was synthesized to load corrosion inhibitor benzotriazole, and the synthesized two-dimensional composite was named as fGS-BTA. Its compatibility and dispersion stability in sol solution was prominently reinforced by amino-silane functionalization. Meanwhile, amino-silane as pH-driven “nanogate” suppressed the premature leakage of inhibitor, which endowed fGS-BTA nanocomposite the stimuli-responsive release under alkaline condition. Electrochemical impedance spectroscopy of intact and scratched sol-gel coating filled with fGS-BTA nanosheets showed the enhanced barrier property and the active protection capacity.

High Co-loading Capacity and Stimuli-Responsive Release Based on Cascade Reaction of Self-Destructive Polymer for Improved Chemo-Photodynamic Therapy.

Photodynamic therapy (PDT) shows a promising synergy with chemotherapy in the therapeutic outcome of malignant cancers. The minimal invasiveness and nonsystemic toxicity are appealing advantages of PDT, but combination with chemotherapy brings in the nonselective toxicity. We designed a polymeric nanoparticle system that contains both a chemotherapeutic agent and a photosensitizer to seek improvement for chemo-photodynamic therapy. First, to address the challenge of efficient co-delivery, polymer-conjugated doxorubicin (PEG-PBC-TKDOX) was synthesized to load photosensitizer chlorin e6 (Ce6). Ce6 is retained with DOX by a π-π stacking interaction, with high loading (41.9 wt %) and the optimal nanoparticle size (50 nm). Second, light given in PDT treatment not only excites Ce6 to produce cytotoxic reactive oxygen species (ROS) but also spatiotemporally activates a cascade reaction to release the loaded drugs. Finally, we report a self-destructive polymeric carrier (PEG-PBC-TKDOX) that depolymerizes its backbone to facilitate drug release upon ROS stimulus. This is achieved by grafting the ROS-sensitive pendant thioketal to aliphatic polycarbonate. When DOX is covalently modified to this polymer via thioketal, target specificity is controlled by light, and off-target delivery toxicity is mostly avoided. An oral squamous cell carcinoma that is clinically relevant to PDT was used as the cancer model. We put forward a polymeric system with improved efficiency for chemo-photodynamic therapy and reduced off-target toxicity.

Stimuli-responsive DOX release behavior of cross-linked poly(acrylic acid) nanoparticles

AbstractCross-linked poly(acrylic acid) nanoparticles were synthesizedviadistillation precipitation polymerization of acrylic acid and ethylene glycol dimethacrylate withdifferent molar ratios. Spherical nanoparticles with diameters between 75 and 122 nm were synthesized and exhibited temperature and pH-responsive behaviors. However, this behavior was less pronounced for samples with higher cross-linking degrees. The potential of all nanoparticles as carriers for controlled release of doxorubicin (DOX) anti-cancer drug was examined at pH values of 1.2, 5.3 and 7.4. An obvious alleviation in burst release behavior and the amount of cumulative drug release was seen for all nanoparticles as the pH of the medium and the cross-linking degree of nanoparticle increased. Also kinetics of drug release was studied using mathematical models of zero-order, first-order, Higuchi, Korsmeyer-Peppas and Hixson-Crowell, where Higuchi and Korsmeyer-Peppas models best defined the kinetics of drug release.

Novel Class of Ultrasound-Triggerable Drug Delivery Systems for the Improved Treatment of Tumors.

The controlled release of anticancer drugs at the tumor site is a central challenge in treating cancer. To achieve this goal, our strategy was based on tumor-specific targeting and ultrasound-triggered release of an anticancer agent from liposomal nanocarriers. To enhance the ultrasound-triggered drug release, we incorporated a lipophilic sonosensitizer, chlorin e6 (Ce6) ester, into the lipid bilayer of liposomes. Additionally, asparagine-glycine-arginine (NGR) that binds to CD13, which is overexpressed in tumor cells, was introduced into these liposomes. Under the navigation effects of the NGR, the novel ultrasound-triggerable NGR-modified liposomal nanocarrier (NGR/UT-L) accumulates in tumor sites. Once irradiated by ultrasound in tumor tissues, the sonodynamic effect produced by Ce6 could create more efficient disruptions of the lipid bilayer of the liposomal nanocarriers. After encapsulating doxorubicin (DOX) as the model drug, the ultrasound triggered lipid bilayer breakdown can spring the immediate release of DOX, making it possible for ultrasound-responsive chemotherapy with great selectivity. By combining tumor-specific targeting and stimuli-responsive controlled release into one system, NGR/UT-L demonstrated a perfect antitumor effect. Moreover, this report provides an example of controlled-release by means of a novel class of ultrasound triggering systems.

A REVIEW ON NANOSPONGES A REVIEW ON NANOSPONGES: A BOON TO TARGETED DRUG DELIVERY FOR ANTICANCER DRUG

In recent decades, the rise in the investigation of new drugs had made health-care system expensive compared to conventional drug delivery systems and techniques. The present drug delivery systems have become highly productive and are growing fast. Majority of the anticancer agent has low water solubility resulting in multistep synthetic routes that require higher selectivity and specificity that can cause difficulty in the development of the formulation. Nanosponges (NSs) are branched cyclodextrin (CD) polymeric systems which have proven to be a boon in the pharmaceutical and biomedical fields. Different kinds of NSs based on different types of CDs and crosslinkers are used for developing of new drug formulations from the past few years for various applications in health care. Nanotechnology has overcome the issues regarding the drug solubility, stability, and other parameters and has attained success in achieving of sustained release, increased activity, improved permeability, delivery of nucleoprotein, the stimuli-responsive release of the drug, and improved drug bioavailability. There is a huge eruption of research on NSs for cancer treatment. Multiple anticancer moieties have been developed, taking into account the pharmacological and physicochemical perspective of the drug to develop a NS formulation. Our target in this review is to catch an efficient and far-reaching NSs for malignancy cancer treatment announced until now. This survey will give a perfect stage for providing details for researchers taking a shot at using new polymers for improving the treatment of the disease using nanotechnology. The present article provides details regarding antineoplastic molecules and provides ideas on CD-based NSs specifically using curcumin, tamoxifen, resveratrol, quercetin, oxygen-NSs, temozolomide, doxorubicin, and 5-fluorouracil (5-FU), and erlotinib (ETB) glutathione.

A dual-functional HER2 aptamer-conjugated, pH-activated mesoporous silica nanocarrier-based drug delivery system provides in vitro synergistic cytotoxicity in HER2-positive breast cancer cells.

Purpose: As well as functioning as a ligand that is selectively internalized by cells overexpressing human epidermal growth factor receptor-2 (HER2), HApt can exert cytotoxic effects by inducing cross-linking and subsequent translocation of HER2 to cytoplasmic vesicles, such downregulation of HER2 inhibits cell proliferation and induces apoptosis. We aimed to exploit the potential of HApt as both a targeting agent and antagonist to maximize the efficacy of mesoporous silica nanoparticle (MSN)-based drug release systems for HER2-positive breast cancer.Materials and methods: We fabricated novel HApt aptamer-functionalized pH-sensitive β-cyclodextrin (β-CD)-capped doxorubicin (DOX)-loaded mesoporous silica nanoparticles (termed MSN-BM/CD-HApt@DOX) for targeted delivery and selective targeting of HER2-positive cells. MSN-functionalized benzimidazole (MSN-BM) was used to load and achieve pH stimuli-responsive release of the chemotherapeutic agent doxorubicin (DOX). β-cyclodextrin was introduced as a gatekeeper for encapsulated DOX and HApt as a selective HER2-targeting moiety and biotherapeutic agent.Results: Physical and chemical characterizations (FT-IR, XRD, TEM and BET) confirmed successful construction of MSN-BM/CD-HApt@DOX nanoparticles. In vitro release assays verified pH-sensitive DOX release. MSN-BM/CD-HApt@DOX (relative DOX concentration, 3.6 μg/mL) underwent HER2-mediated endocytosis and was more cytotoxic to HER2-positive SKBR3 cells than HER2-negative MCF7 cells. MSN-BM/CD-HApt@DOX also exhibited better uptake and stronger growth inhibition in SKBR3 cells than the control MSN-BM/CD-NCApt@DOX functionalized with a scrambled nucleotide sequence on CD. Overall, intracellular delivery of DOX and the biotherapeutic agent HApt resulted in synergistic cytotoxic effects in HER2-positive cancer cells in comparison to either DOX or HApt alone.Conclusion: MSN-BM/CD-HApt@DOX enables HER2-mediated targeting and biotherapeutic effects as well as pH-responsive DOX drug release, resulting in synergistic cytotoxic effects in HER2-overexpressing cells in vitro. This novel nanocarrier could potentially enable specific targeting to improve the efficacy of chemotherapy for HER2-positive cancer.

Ultrasonic-assisted fabrication and release kinetics of two model redox-responsive magnetic microcapsules for hydrophobic drug delivery

The smart biocompatible carriers have an advantage in the high-efficiency delivery and stimuli-responsive release of drugs. This study describes two model magnetic microcapsules (MMC) fabricated by sonicating the hydrophobic drug-loaded oil phase in an albumin aqueous solution, where magnetic nanoparticles are either encapsulated into the core or embedded onto the albumin shell. The as-prepared MMC with magnetic shell (MS) or with magnetic core (MC) shows an appropriate dispersibility with a well-defined spherical morphology in water, an excellent magnetism-mediated shifting ability for targeted drug delivery, and a good biocompatibility for high-level cell viability. Moreover, both the two microcapsules also show a high efficiency to trap the hydrophobic drugs, where the embedding ratios are 87.41% for MMC-MS and 95.31% for MMC-MC, respectively. Meanwhile in current study, the release kinetics and mechanism reveal that the sulfhydryl-crosslinked shell structure endows the MMC with a redox-responsive behavior to release the contents for controlled drug release, and the release rate or the release amount can be adjusted by changing the dosage of reducing agent. Therefore, the MMC have great potential as a smart carrier of hydrophobic drugs for enhancing the therapeutic efficiency.

Nucleic Acid-Based Functional Nanomaterials as Advanced Cancer Therapeutics.

Nucleic acid-based functional nanomaterials (NAFN) have been widely used as emerging drug delivery nanocarriers for cancer therapeutics. Considerable works have demonstrated that NAFN can effectively load and protect therapeutic agents, and particularly enable targeting delivery to the tumor site and stimuli-responsive release. These outstanding performances are due to NAFN's unique properties including inherent biological functions and sequence programmability as well as biocompatibility and biodegradability. In this Review, the recent progress on NAFN as advanced cancer therapeutics is highlighted. Three main cancer therapy approaches are categorized including chemo-, immuno-, and gene-therapy. Examples are presented to show how NAFN are rationally and exquisitely designed to address problems in cancer therapy. The challenges and future development of NAFN are also discussed toward future more practical biomedical applications.

PH and GSH dual responsive smart silica nanocarrier for doxorubicin delivery

Drug delivery system (DDs) should include stimuli-responsive release at the target sites. With this goal, pH and Glutathione (GSH) microenvironment triggering mesoporous silica nanoparticles (MSNs) were prepared. In this system, the ZnO Quantum Dots, as a gatekeeper is bonded to the silica nanocarrier via a cleavable disulfide bond. ZnO QDs have the potential to be used as a gatekeeper due to, its acidic dissolution to Zn 2+ ions. Doxorubicin hydrochloride (Dox), an effective chemotherapeutic drug, is used to investigate the release behavior. Under physiological pH, ZnO QDs is stable, which resulted in blocked drugs inside the pores. Under the acidic pH, grafted ZnO QDs is removed due to its acidic dissolution, which resulted in the pore opening and releasing of the drug. Besides pH stimuli, the release of the drug was triggered by GSH.

Sulfonate-Functionalized Mesoporous Silica Nanoparticles as Carriers for Controlled Herbicide Diquat Dibromide Release through Electrostatic Interaction.

Environmental stimuli-responsive pesticide release is desirable for enhanced efficiency and reduced side effects. In most cases, the loading and release of pesticides mainly depends on hydrophobic interactions and hydrogen bonding. Electrostatic interaction is less investigated as a weapon for achieving high loading content and controlled pesticide release. In this work, negative-charge decorated mesoporous silica nanoparticles (MSNs) were facilely fabricated by introducing sulfonate groups onto MSNs through a post-grafting method. Sulfonate-functionalized MSNs (MSN-SO3) were synthesized by conversion of epoxy group into sulfonate group using a bisulfite ion as a ring opening reagent. Diquat dibromide (DQ), one of the globally used quaternary ammonium herbicides, was efficiently loaded into these negatively charged MSN-SO3 nanoparticles. The loading content was increased to 12.73% compared to those using bare MSNs as carriers (5.31%). The release of DQ from DQ@MSN-SO3 nanoparticles was pH and ionic strength responsive, which was chiefly governed by the electrostatic interactions. Moreover, DQ@MSN-SO3 nanoparticles exhibited good herbicidal activity for the control of Datura stramonium L., and the bioactivity was affected by the ionic strength of the release medium. The strategy of cargo loading and release dependent on the electrostatic interactions could be generally used for charge-carrying pesticides using carriers possessing opposite charges to mitigate the potential negative impacts on the environment.

Biodegradable hybrid mesoporous silica nanoparticles for gene/chemo-synergetic therapy of breast cancer.

Mesoporous silica nanoparticles have been extensively explored in anticancer nanomedicine due to their excellent biodegradability, which is one important focus in their further clinical translations. However, the traditional design concepts based on the functional modification with active groups cannot significantly improve the controlled drug release efficiency and anticancer effect. Herein, a molecularly organic-inorganic hybrid mesoporous silica nanoparticle (HMSN) nanocarrier coated with hyaluronic acid (HA) and polyethyleneimine (PEI) was constructed for the gene/chemo-synergetic therapy of breast cancer. Notably, HMSN with tumor-sensitive disulfide bond and targeting ligand HA can be decomposed when it encounters high concentration of glutathione (GSH) and hyaluronidase (HAase). The biodegradability of host molecules and the fast disintegration of the framework in tumor microenvironment can also accelerate the stimuli responsive release of cargos inside the pore space. Furthermore, the grafting of polyethyleneimine (PEI) could increase gene loading efficiency. From the above, the smart approach involves a combination of biodegradability and biological effect and results in synergetic antitumor effect of gene and chemical drug on breast cancer. All these findings demonstrated that HMSN/HA/PEI nanocarriers can be suitable for biomedical application, paving the way to fast development of multi-functional nano-biomedicine.

Nonmagnetic Hypertonic Saline-Based Implant for Breast Cancer Postsurgical Recurrence Prevention by Magnetic Field/pH-Driven Thermochemotherapy.

Magnetic-mediated hyperthermia (MMT) is emerging as one of the promising techniques, which could synergistically treat cancer along with current treatment techniques such as chemotherapy and radiotherapy and trigger on-demand release of therapeutic macromolecules. However, the low specific absorption rate and potential in vivo toxicity of magnetic nanomaterials as the MMT mediators restrict the new advancements in MMT treatment. Herein, for the first trial, the unique inductive heating property of hypertonic saline (HTS), a clinically applied solution exhibiting several physiological effects under alternative magnetic field (AMF), was systematically investigated. Though without magnetic property, due to the dipolar polarization under the electromagnetic radiation, HTS can induce enough high and rapid temperature increase upon exposure under AMF. Based on such an observation, PEG-based HTS hydrogel was fabricated for the inhibition of unwanted diffusion of ions so as to ensure the ideal temperature rise at the targeted region for a longer time. Furthermore, an anticancer drug (doxorubicin) was also incorporated into the hydrogel to achieve the magnetic field/pH stimuli-responsive drug-sustainable release as well as synergistic thermochemotherapy. The potential application of the drug-loaded HTS-PEG-injectable hydrogel for breast cancer postsurgical recurrence prevention is demonstrated. Significant in vivo suppression of two kinds of breast cancer models was achieved by the hybrid hydrogel system. This work explores a new biomedical use of clinical HTS and a promising cancer treatment protocol based on HTS-PEG hydrogel for magnetic hyperthermia combined with stimuli-responsive chemotherapy for breast cancer postsurgical recurrence prevention.

Free-standing microchamber arrays as a biodegradable drug depot system for implant coatings

The combination of an efficient encapsulation method of small water-soluble substances with a stimuli-responsive release of defined quantity remains a challenging task. A novel drug delivery system (DDS) representing a free-standing PLLA microchamber arrays film and its application as the cover for implantable endovascular stent are reported in this work. The proposed DDS preparation method is consisting of a patterned polydimethylsiloxane (PDMS)-stamp dip-coated into a polymer solution followed by drug loading and sealing it by polymer pre-coated substrate. It was shown that using 1 wt% PLLA solution is optimal for obtaining microchamber arrays with an individual cargo capacity of 2.88 × 10−9 µg, which was successfully loaded by model drug substance Rhodamine B. Rhodamine B was completely released in vitro during 13 days in PBS at 37 °C by diffusion. It was demonstrated that low-frequency ultrasound (LFUS, 20 kHz) allows triggering RhB release due to microchamber damage and detachment of individual PLLA microchambers over time. LFUS exposure time up to 25 s led to RhB release of up to 8.4 × 10−4 µg (approximately 55%) from microchambers located on the flat substrate; up to 5.2 × 10−4 µg from microchambers located on the stent with using a simplified vessel model. Furthermore, the free-standing printed PLLA microchamber arrays were demonstrated to be applied as endovascular stent cover that can be used for complementary pharmacological effect, for example, triggered local delivery of anticoagulants.

Stimulus-Responsive Antibiotic Releasing Systems for the Treatment of Wound Infections.

There remains an unmet need for innovative treatments for chronic wound infections as they continue to be a financial and social burden on society. Because of the dynamic nature of wounds, this study investigated the utilization of stimulus-responsive plasma polymers for the development of pH- and thermoresponsive antibiotic delivery systems for the treatment of wound infections. Porous silicon films were loaded with the antibiotic levofloxacin (LVX) and subsequently coated with plasma polymer layers: first, poly(1,7-octadiene) (pOCT) for stability, followed by either the temperature-responsive polymer poly N,N-diethylacrylamide (pDEA) or the pH- responsive polymer poly 2-(diethylamino)ethyl methacrylate (pDEAEMA), to fabricate two delivery systems. The delivery systems were thoroughly characterized chemically and physically and tested in vitro through drug release and bacterial zone of inhibition studies. After a 16 h time point, the system containing pDEA achieved 3.2-fold greater release at 45 °C compared to 22 °C, whereas the system containing pDEAEMA achieved a 2.2-fold greater release when exposed to pH 8.5 media compared to pH 6.2 media. Furthermore, both systems retained their antimicrobial activity and demonstrated stimulus-responsive release to form zones of inhibition on relevant wound pathogens, Pseudomonas aeruginosa, Staphylococcus epidermidis and Staphylococcus aureus. Therefore, this proof-of-principle study confirms that stimulus-responsive porous silicon films can be utilized to deliver antibiotic when exposed to physiologically relevant stimuli such as pH and temperature with the potential to be applied to other pharmaceutics.

Development and characteristics of novel sonosensitive liposomes for vincristine bitartrate

The aim of drug delivery is to increase therapeutic efficacy. Externally triggered drug delivery systems enable site-specific and time-controlled drug release. To achieve this goal, our strategy was based on ultrasound-triggered release of an anticancer agent from sonosensitive liposomes (SL). To realize the ultrasound-triggered drug release, a lipophilic sonosensitizer, hematoporphyrin monomethyl ether (HMME) was incorporated into the lipid bilayer of liposomes. Once irradiated by the ultrasound in tumor tissues, the sonodynamic effect generated by HMME could lead to an efficient disruption of the lipid bilayer in the SL. After encapsulating vincristine bitartrate (VIN) as the model drug, the ultrasound-triggered lipid bilayer breakdown can trigger the instant release of VIN, enabling ultrasound-controlled chemotherapy with great specificity. In the in vitro and in vivo studies, by integrating tumor-specific targeting and stimuli-responsive controlled release into one system, VIN-loaded SL showed excellent antitumor efficacy. The SL could potentially produce viable clinical strategies for improved targeting efficiency of VIN for the treatment of related cancer. More importantly, this report provides an example of controlled release by means of a novel class of ultrasound triggering system.

Recent advancement of imidazolate framework (ZIF-8) based nanoformulations for synergistic tumor therapy.

As a new kind of porous material, zeolitic imidazolate frameworks (ZIF-8) are built from zinc ions and 2-methylimidazolate and possess unique merits including high porosity, good structural regularity and tunability, adjustable surface functionality and intrinsic pH induced biodegradability. These advantages endow ZIF-8 with multiple functionalities and stimuli-responsive controlled release of loaded payloads by endogenous or exogenous means. In this review, we will summarize the recent advancement of ZIF-8 as nanocarriers for the loading of various molecules including chemotherapeutic drugs, photosensitizers, photothermal agents, and proteins to fabricate multifunctional nanocomposites for synergistic cancer therapy. In addition, the challenges and future developments in this area will be highlighted.

Preparation of a one-dimensional nanorod/metal organic framework Janus nanoplatform via side-specific growth for synergistic cancer therapy.

Janus nanoparticles (JNPs) have emerged in recent years as new compartmentalized colloids with two sides of different components, chemical properties or morphologies that have opened up a wide range of unique applications in biomedicine. Here, we explored a unique lactobionic acid (LA) modified metallic one-dimensional nanorod/metal organic framework (1D NR/MOF) JNP, the LA-gold NR/zeolitic imidazolate framework-8 (LA-AuNR/ZIF-8) JNP, for computed X-ray tomography (CT) image-guided liver cancer targeted synergistic chemo-photothermal theranostics. Taking advantage of the 1D nanostructure of the AuNRs, polyacrilic acid (PAA) was selectively attached to one side of the AuNRs for further growth of ZIF-8, and the exposed side of the AuNRs was modified with the targeting agent LA, thus realizing the drug loading and cancer specific targeting. In addition, the high contrast of Au makes the LA-AuNR/ZIF-8 JNPs suitable for CT image-guided cancer therapy. Furthermore, mice treated with doxorubicin (DOX) loaded LA-AuNR/ZIF-8 JNPs under near infrared (NIR) laser irradiation showed significant tumor inhibition, indicating the effective combination of pH and NIR stimuli response release, cancer specific targeting and synergistic chemotherapy and photothermal therapy.

Stimuli-responsive multifunctional metal-organic framework nanoparticles for enhanced chemo-photothermal therapy.

Construction of stimuli-responsive multifunctional nanoparticles is critical for nanotherapeutic delivery. Though metal-organic frameworks (MOFs) have been emerged as promising delivery vehicles, the therapeutic efficacy of MOFs in cancer treatment is limited by the lack of a general approach for the preparation of stimuli-responsive multifunctional MOFs. We show that the combination of a versatile coating material polydopamine with MOFs enables facile integration of different functional therapeutics, obtaining stimuli-responsive multifunctional MOFs with extensive photothermal efficiency and outstanding capability to abrogate tumors by chemo-photothermal therapy. Exemplary MOFs including ZIF-8, UiO-66, and MIL-101 were utilized to prepare stimuli-responsive multifunctional MOFs to illustrate the generality of the strategy. This approach enables targeted drug delivery and stimuli-responsive release of multi-therapeutics and allows combination therapy with excellent in vitro and in vivo antitumor activity. Taking into account the diversity of MOFs and different functional molecules, this work provides flexible access to programmable MOF nanoparticles for specific biological applications.

Smart Metal-Organic Framework-Based Nanoplatforms for Imaging-Guided Precise Chemotherapy.

Good biocompatibility, active tumor targeting, and stimulus-responsive release offer great opportunity for precise imaging-guided tumor treatment. However, the current strategies for the fabrication of smart theranostic platforms suffer from tedious synthesis processes. Here, we propose a universal and facile strategy for the fabrication of smart nanoscale metal-organic framework (NMOF)-based nanoplatforms for imaging-guided precise chemotherapy. As a proof of concept, 5-boronobenzene-1,3-dicarboxylic acid (BBDC), as a versatile ligand, was employed for the first time with Gd3+ as metal nodes to prepare a smart magnetic resonance (MR) imaging-guided drug-delivery system. Specific reversible diol-borate condensation enables effortless coating of glucose on the NMOFs to improve their biocompatibility. The specific interaction between glucose and glucose-transported protein ensures active tumor-targeting ability. Moreover, the glucose layer, as a pH-responsive diol-borate gatekeeper, prevents the premature leakage of drugs. The proposed smart theranostic nanoplatform was well used in MR imaging-guided tumor-targeted precise chemotherapy. This strategy is simply extended to the design of other MOF-glucose composites for diverse applications, such as X-ray computed tomography imaging of gastrointestinal tract with Yb-MOFs-Glu. BBDC, as a functional ligand, provides a simple and universal way to fabricate smart NMOF theranostic platforms with multifunction as "three birds with one stone". The facile and universal strategy lays down a new way to develop multifunctional nanoagents for precision medicine.