Development of a pH-sensitive functionalized metal organic framework: in vitro study for simultaneous delivery of doxorubicin and cyclophosphamide in breast cancer

Exploration of an efficient dual-drug based nanocarrier with high drug loading capacity, specific targeting properties, and long-term stability is highly desirable in cancer therapy. Metal–organic frameworks (MOFs) have proven to be a promising class of drug carriers due to their high porosity, crystalline properties with defined structure information, and their potential for further functionalization. To enhance the drug efficacy as well as to overcome the burst effect of drugs, here we synthesized a pH responsive folic acid (FA) and graphene oxide (GO) decorated zeolitical imidazolate frameworks-8 (GO–FA/ZIF-8), for targeted delivery of doxorubicin (DOX) and cyclophosphamide (CP), simultaneously. In this system, DOX molecules were encapsulated in the pores of ZIF-8 during in situ synthesis of ZIF-8 and CP molecules have been captured by the GO surface via hydrogen bonding and π–π interactions as well. Furthermore, the resulting pH-responsive nanocarrier (DOX@ZIF-8/GO–FA/CP) showed in vitro sustained release characteristics (76% of DOX and 80% of CP) by cleavage of chemical bonding and disruption of the MOFs structure under acidic condition (at pH 5.6). Moreover, DOX@ZIF-8/GO–FA/CP has synergistic cytotoxic effects as compared to the combination of both the drugs without ZIF-8/GO–FA when treating MCF-7 and MDA-MB-231 breast cancer cell lines (with a combination index of 0.29 and 0.75 for MCF-7 and MDA-MB-231 cell-lines, respectively). Hence this system can be applied as an effective platform for smart dual drug delivery in breast cancer treatment through its remarkable manageable multidrug release.

Exploration of an efficient dual-drug based nanocarrier with high drug loading capacity, specific targeting properties, and long-term stability is highly desirable in cancer therapy.     

Engineering pH-responsive switching of donor–π–acceptor chromophore alignments along a peptide nanotube scaffold

A cyclic tri-β-peptide cyclo(β-Ala-β-Ala-β-Lys) having diethylaminonaphthalimide at the β-Lys side chain (CP3Npi) self-assembled into a peptide nanotube in a solution of HFIP and water. CD spectra of the CP3Npi nanotubes show a negative Cotton effect at 441 nm and a positive Cotton effect at 393 nm, indicating that D–π–A naphthalimide chromophores are aligned in a left-handed chiral way along the nanotube. The CP3Npi nanotubes bear positive charges under acidic conditions retaining the nanotube structure but pH-responsive switching of D–π–A naphthalimide alignments along the nanotube between a left-handed chiral and random arrangement was observed. The peptide nanotube is a stable scaffold for attaining pH-responsive alignment switching of side-chain chromophores.

pH-Responsive switching between a left-handed chiral and random alignments of D–π–A naphthalimides along a peptide nanotube (PNT) composed of tri-β-cyclic peptides was attained in response to repeated pH changes.     

Tunable surface wettability and pH-responsive 2D structures from amphiphilic and amphoteric protein microfibrils

Two dimensional films and paper-like structures (60–170 μm thick) have been facilely fabricated by casting ethanolic dispersions of amphiphilic and amphoteric protein microfibrils (ca. 1.3 μm width; 53 μm length) under controlled temperatures and moisture levels. Surface hydrophilicity or hydrophobicity can be easily tuned by the abillity of the highly responsive microfibers to self-organize at the interface to mimic the hydrophilicity or hydrophobicity of cast substrates. For instance, surfaces cast on hydrophobic polystyrene or Teflon were moderately hydrophobic with water contact angles (WCAs) of 54°–71° while those on hydrophilic glass or exposed to air were hydrophilic (WCAs: 5°–10°). Thin film dried in the presence of moisture (60% RH) at 65 °C had the highest crystallinity (CrI: 56%) and β structure (64%), including 48% β-sheet form, and exhibited moisture-responsive T_g, pH-responsive planar swelling, and excellent wet resiliency in extremely acidic (pH = 0) to basic (pH = 10) conditions. The pH-dependent release of highly water-soluble cationic methylene blue bound to protein microfibril (SPMF) films attests to their amphoterism and demonstrates the applicability of such 2D structures for pH-dependent controlled release of other cationic and anionic species. Such versatility of amphiphilic and amphoteric protein microfibrils can be engineered into 2D structures with tunable surface hydrophilicity and hydrophobicity, moisture- and pH-responsive behaviors and controlled release capabilities.

2D structures from amphiphilic and amphoteric protein microfibrils with tunable surface amphiphilicity, pH-responsive controlled release of cationic and anionic species.     

Polymer grafted magnetic graphene oxide as a potential nanocarrier for pH-responsive delivery of sparingly soluble quercetin against breast cancer cells

In this work, polymer grafted magnetic graphene oxide (GO–PVP–Fe₃O₄) was successfully synthesized for efficient delivery of anticancer drug. Firstly, GO was functionalized with the hydrophilic and biocompatible polymer polyvinylpyrrolidone (PVP) and then grafted with magnetic nanoparticles (Fe₃O₄) through an easy and effective chemical co-precipitation method. Quercetin (QSR) as an anticancer drug was loaded onto the surface of GO–PVP–Fe₃O₄via non-covalent interactions. The drug loading capacity was as high as 1.69 mg mg⁻¹ and the synthesized magnetic nanocarrier shows pH-responsive controlled release of QSR. The cellular cytotoxicity of the synthesized nanocarrier with and without drugs was investigated in human breast cancer MDA MB 231 cells and their effects compared on non-tumorigenic epithelial HEK 293T cells. These results reveal that the drug loaded GO–PVP–Fe₃O₄ nanohybrid was found to be more toxic than the free drug towards MDA MB 231 cells and exhibits biocompatibility towards HEK 293T cells. Overall, a smart drug delivery system including polymer grafted magnetic graphene oxide as a pH-responsive potential nanocarrier could be beneficial for targeted drug delivery, controlled by an external magnetic field as an advancement in chemotherapy against cancer.

Polymer grafted magnetic graphene oxide (GO–PVP–Fe₃O₄) as an efficient nanocarrier for the delivery of anticancer drug quercetin.     

Switchable conformational changes of DNA nanogel shells containing disulfide–DNA hybrids for controlled drug release and efficient anticancer action

Oligonucleotide strands containing dithiol (–SS–) groups were used as the co-crosslinkers in PNIPA–AAc based nanogels (NGs). They hybridized with PEG–oligonucleotides introduced into the gels. The specific DNA hybrid formed in the nanogel/nanocarrier was involved in highly efficient accumulation of intercalators. The presence of –SS– groups/bridges improved the storing efficiency of doxorubicin (Dox) in DNA hybrids by 53, 40 and 20% compared to regular, single stranded and regular double stranded DNA crosslinkers, respectively. The explicit arrangement of the hybrids in the carrier enabled their reduction by glutathione and an effective cancer treatment while the side toxicity could be reduced. Compared to the NGs with traditional crosslinkers and those containing typical dsDNA-based hybrids, an improved, switchable and controlled drug release occurred in the novel NGs. Since the novel NGs can release the oligonucleotide strands during their degradation, this gives an opportunity for a combined drug-gene therapy.

Switchable conformational changes of multiresponsive nanogels containing disulfide/DNA hybrid shells for pulsative drug release.     

A reversible,colorimetric, pH-responsive indole-based hydrogel and its application in urea detection

A new type of pH-responsive indole-based (4-HINF) hydrogel, fabricated by a sol–gel method, was utilized as a platform for colorimetric detection of urea in aqueous solution. The colorimetric sensor was established by virtue of the synergistic effect of cation–π interaction and hydrogen bonding with good regenerative ability. The results exhibited linear response in the range of 0–10 mM with a limit of detection of 10 μM. The prepared 4-HINF hydrogel possessed high selectivity to pH change under complicated environments ensuring further applications in environmental and bio-systems.

A new type of pH-responsive indole-based (4-HINF) hydrogel, fabricated by a sol–gel method, was utilized as a platform for colorimetric detection of urea in aqueous solution.     

Release kinetics study and anti-corrosion behaviour of a pH-responsive ionic liquid-loaded halloysite nanotube-doped epoxy coating

This study focuses on the release kinetics of inhibitor-loaded nanocontainers and the anti-corrosive properties of epoxy coatings doped and undoped with the nanocontainers. In this work, 1-butyl-3-methylimidazolium chloride [Bmim][Cl] was loaded into halloysite nanotubes (HNTs), and the loaded HNTs were encapsulated with polyethyleneimine (PEI)/polyacrylic acid (PAA) and poly(diallyldimethylammonium chloride) (PDADMAC)/polyacrylic acid (PAA) to allow controlled release upon pH stimuli. The polyelectrolyte layer deposition was characterized using zeta potential analysis, and the release profiles were evaluated in neutral, acidic, and alkaline media. The release kinetics was studied and found to conform to the Ritger–Peppas and Korsmeyer–Peppas model, and the results proved that the combination of weak polyelectrolytes (PEI and PAA) provided a good response for up to 50% release of [Bmim][Cl] in acidic and alkaline media after 72 hours. The loaded HNTs encapsulated with the PEI/PAA combination were incorporated into an epoxy coating matrix and applied on an X52 steel substrate. The corrosion resistance of the coated and uncoated substrates was evaluated using electrochemical impedance spectroscopy (EIS) after immersion in a 3.5 wt% NaCl solution up to 72 hours. An artificial defect was created on the coating prior to immersion to evaluate the active corrosion inhibition ability. The coating doped with the smart pH-responsive halloysite nanotubes showed promising results in corrosion protectiveness even after 72 hours of exposure to a salt solution through EIS and SEM.

Enhanced corrosion resistance was obtained for steel coated with epoxy resin doped with pH-responsive halloysite nanotubes loaded with ionic liquid.     

Morphology-dependent pH-responsive release of hydrophilic payloads using biodegradable nanocarriers

The development of functional nanocarriers with stimuli-responsive properties has advanced tremendously to serve biomedical applications such as drug delivery and regenerative medicine. However, the development of biodegradable nanocarriers that can be loaded with hydrophilic compounds and ensure its controlled release in response to changes in the surrounding environment still remains very challenging. Herein, we achieved such demands via the preparation of aqueous core nanocapsules using a base-catalyzed interfacial reaction employing a diisocyanate monomer and functional monomers/polymers containing thiol and hydroxyl functionalities at the droplet interface. pH-responsive poly(thiourethane–urethane) nanocarriers with ester linkages were synthesized by incorporating polycaprolactone diol, which is susceptible to hydrolytic degradation via ester linkages, as a functional monomer in the reaction formulation. We could demonstrate that by systematically varying the number of biodegradable segments, the morphology of the nanocarriers can be tuned without imparting the efficient encapsulation of hydrophilic payload (>85% encapsulation efficiency) and its transfer from organic to aqueous phase. The developed nanocarriers allow for a fast release of hydrophilic payload that depends on pH, the number of biodegradable segments and nanocarrier morphology. Succinctly put, this study provides important information to develop pH-responsive nanocarriers with tunable morphology, using interfacial reactions in the inverse miniemulsion process, by controlling the number of degradable segments to adjust the release profile depending on the type of application envisaged.

The morphology and release properties of aqueous core nanocapsules for the pH-responsive release of hydrophilic payload was investigated by systematically varying the number of biodegradable segments.     

One-step dry synthesis of an iron based nano-biocomposite for controlled release of drugs

Bio-based drug carriers have gained significant importance in Control Drug Delivery Systems (CDDS). In the present work, a new iron-based magnetic nano bio-composite (nano-Fe-CNB) is developed in a one-step dry calcination process (solventless) using a seaweed-based biopolymer. The detailed analysis of the developed nano Fe-CNB is carried out using FE-SEM, HR-TEM, P-XRD, XPS, Raman spectroscopy, FTIR etc. and shows that nano-Fe-CNB consists of nanoparticles of 5–10 nm decorated on 7–8 nm thick 2-D graphitic carbon material. The impregnation of nano-Fe-CNB into the calcium alginate (CA) hydrogel beads is found to have good drug loading capacity as well as pH responsive control release behavior which is demonstrated using doxorubicin (DOX) as a model cancer drug. The drug loading experiments exhibit ∼94% loading of DOX and release shows ∼38% and ∼8% release of DOX at pH 5.4 and 7.4 respectively. The developed nano Fe-CNB facilitates strong electrostatic interactions with cationic DOX molecules at pH 7.4 and thereby restricts the release of the drug at physiological pH. However, at cancer cell pH (5.4), the interaction between the drug and nano-Fe-CNB reduces which facilitates more drug release at pH 5.4. Thus, the developed nano-biocomposite has the potential to reduce the undesired side effects associated with faster release of drugs.

Schematics for synthesis and application of magnetic nano-biocomposite for control release of DOX.     

Mussel inspired ZIF8 microcarriers: a new approach for large-scale production of stem cells

Metal–organic frameworks (MOFs) have high porosity, large surface area, and tunable functionality and have been widely used for drug loading. The aim of this study was to exploit unique features of zeolitic imidazolate framework-8 (ZIF8) to develop an innovative composite microcarrier (MC) for human mesenchymal stem cells (hMSCs) adhesion and proliferation. ZIF8 MCs were prepared by immobilization of polydopamine/polyethyleneimine (PDA/PEI) and ZIF8 on the surface of polystyrene beads. The chemical properties of MCs such as coating stability and homogeneity were characterized by different techniques such as ATR-FTIR, XRD, EDX, SEM, and contact angle. The prepared MCs were tested using human adipose-derived mesenchymal stem cells (hADSCs) in both static and dynamic conditions, and results were compared to a commercially available MC (Star-Plus), polydopamine coated MCs and amine-functionalized MCs as a control. Results show that PDA/PEI/ZIF8 coated MCs (in short: ZIF8 MCs) provides an excellent biocompatible environment for hADSCs adhesion and growth. In conclusion, ZIF8 MCs represent suitable and low-cost support for hADSCs culture and expansion, which can maximize cell yield and viability while preserving hADSCs multipotency. The present findings have revealed this strategy has the potential for chemical and topographical modification of MCs in tissue engineering applications.

Mussel inspired ZIF8 microcarriers with high surface area, biocompatibility, and nanoscale surface roughness are applied to enhance mesenchymal stem cell attachment and proliferation in 3D cell culture.     

Reasons for enhanced activity of doxorubicin on co-delivery with octa(3-aminopropyl)silsesquioxane

This paper presents results of spectroscopic (NMR, FTIR, fluorescence), Q-TOF mass spectrometry and Z-potential analyses of interactions between octa(3-aminopropyl)silsesquioxane hydrochloride (POSS-NH₂·HCl) and anticancer drug – doxorubicin hydrochloride. These studies aimed at explanation of the enhanced activity of doxorubicin on co-delivery with POSS-NH₂. The results point to the formation of active complexes via ionic interactions between the ammonium chloride groups of silsesquioxane and the drug, and not, as suggested earlier, via NH⋯N hydrogen bonding. It has also been shown that the main driving force for the formation of the complexes can be strengthened by π–π stacking and hydrogen bonds. The experimental results are supported by quantum mechanical calculations. This work has proven that co-delivery with POSS offers a potentially advantageous and simple approach for improved efficacy in chemotherapy, avoiding often complicated synthesis of conjugates, involving covalent bonding between drug, nanocarrier and targeting agents.

The interaction between polyhedral oligomeric silsesquioxane (POSS) and doxorubicin, leading to formation of active complexes involving POSS functional aminopropyl groups and anthracycline functional groups.     

Folic acid and deoxycholic acid derivative modified Fe3O4 nanoparticles for efficient pH-dependent drug release and multi-targeting against liver cancer cells

The novel nano-drug carrier (FDCA-FA-MNPs) was constructed by grafting formyl deoxycholic acid (FDCA) and folic acid (FA) on the surface of Fe₃O₄ magnetic nanoparticles (MNPs), possessing the advantages of superparamagnetism, good stability, low cytotoxicity and good blood compatibility. The hydrophobic anti-cancer drug doxorubicin hydrochloride (DOX) was successfully loaded onto FDCA-FA-MNPs through supramolecular interactions (hydrogen bond between FDCA and drug and hydrophobic interaction and π–π stacking between drug and drug). The drug loading amount and drug loading capacity were 509.1 mg g⁻¹ and 33.73 wt%, respectively. In addition, drug release had a pH responsive and controllable release performance, the release rate at pH 5.3 (45.6%) was four times that at pH 7.4 (11.5%), and the tumor microenvironment was favorable for drug release. More importantly, the novel nano-drug carrier combined the hepatocellular targeting of FDCA, the cancer cell targeting of FA, and the magnetic targeting of Fe₃O₄, showing excellent cancer-killing efficiency (78%) in vitro. Therefore, the nano-drug carrier synthesized in this paper has potential practical application value in the targeted therapy of liver cancer.

A nano-drug carrier, FDCA-FA-MNPs was constructed by modifying Fe₃O₄ magnetic nanoparticles (MNPs) with formyl deoxycholic acid (FDCA) and folic acid (FA) with double-targeting, pH-triggered drug release and excellent tumor cell killing efficiency.     

Nisin/polyanion layer-by-layer films exhibiting different mechanisms in antimicrobial efficacy

Nisin/polyanion Layer-by-Layer (LbL) films are reported to exhibit different mechanisms in antimicrobial efficacy depending on the type of polyanion. LbL films consisting of nisin as the polycationic component were prepared using two different polyanionic constituents: poly acrylic acid (PAA) and dextran sulfate (DX). Due to the weaker interaction strength of carboxylate groups with nisin compared to sulfate/nisin, a larger molecular weight of PAA was needed to achieve LbL assembly. PAA-100K/nisin and DX-15K/nisin multilayer films exhibited significantly different properties. PAA–nisin films grew faster compared to DX–nisin films and showed, for 60 bilayer films, an average bilayer thickness of 21.6 nm compared to that of 6.1 nm in DX–nisin films. The total amount of nisin was found to be 17.1 ± 2.2 μg cm⁻² in (PAA–nisin)₆₀ and 6.8 ± 0.4 μg cm⁻² in (DX–nisin)₆₀ films. The stability of the films was investigated at three different pH values of 6.0, 7.4 and 9.5. (PAA–nisin)₆₀ films exhibited the release of nisin into the solution which resulted in the disintegration of the film over several hours. A burst release was observed in the first hour followed by a slower release and disintegration over 24 hours with a complete release at pH 9.5. The bacterial growth inhibition test against Staphylococcus epidermidis confirmed the antimicrobial activity of nisin released from PAA–nisin films. PAA was found to stabilize nisin and the film-released nisin retained its antimicrobial activity in the neutral and alkaline pH values. Unlike PAA–nisin films, (DX–nisin)₆₀ films were stable at the physiological conditions up to 14 days with no release of nisin. DX–nisin films were found to inhibit the attachment of Staphylococcus epidermidis and prevent biofilm formation. These results clearly demonstrate the effect of different polyanions on nisin LbL films to achieve different mechanisms in antimicrobial efficacy and show the potential of PAA–nisin multilayer films as promising local delivery systems for treatment of burns and wounds, while DX–nisin multilayer films can be employed as stable coatings against bacterial attachment and biofilm formation.

Polyanion–nisin multilayer films exhibit antimicrobial activity by controlled release of nisin or as stable biofilm inhibiting coatings depending on polyanion.     

pH-sensitive CAP/SiO2 composite for efficient co-delivery of doxorubicin and siRNA to overcome multiple drug resistance

Long-term administration of chemotherapeutic agents often leads to multiple drug resistance (MDR), which greatly impairs the treatment outcome. To overcome this problem, a biodegradable nanocarrier based on an acid-sensitive calcium phosphate/silica dioxide (CAP/SiO₂) composite was constructed for the codelivery of drug and siRNA. Anticancer drug doxorubicin (DOX) was encapsulated into the composite scaffold by interacting with the exposed Ca²⁺ of CAP/SiO₂ to achieve high drug loading (180 μg mg⁻¹). With further decoration of siRNA, the nanocarrier was applied to enhance the therapeutic efficacy by silencing MDR-relevant genes (P-gp) of DOX-resistance K562/ADR cancer cells. Benefiting from the intrinsic acid degradability of CAP/SiO₂, the nanocomposite demonstrated pH-responsive release behavior, favoring drug/siRNA release within acidic endo-/lysosomes. Consequently, due to the drug and gene effects, this biodegradable nanomedicine demonstrated enhanced therapeutic efficiency, providing a novel strategy for cancer therapy.

CAP/SiO₂ composite with good biocompatibility and acid biodegradability has been prepared. The proposed drug and gene codelivery system based on it demonstrated enhanced therapeutic efficacy for multiple drug resistance cells.     

D–A–D 2H-benzo[d][1,2,3]triazole derivatives as p-type semiconductors in organic field-effect transistors

A series of Donor–π–Acceptor–π–Donor compounds based on a 2H-benzo[d][1,2,3]triazole core branched with different alkynyl donor groups has been characterized and tested in organic field-effect transistors (OFETs). The electronic and molecular structures were elucidated through optical and vibrational spectroscopy in conjunction with DFT calculations. The results indicate that the planarity of the structure and the good intramolecular charge transfer from the electron-donating to the electron-withdrawing fragments play a critical role in the application of the compounds as semiconductors in OFET devices. The compounds were tested in a top-contact/bottom-gate thin film transistor architecture, and they behave as p-type semiconductors.

A series of Donor–π–Acceptor–π–Donor compounds based on a 2H-benzo[d][1,2,3]triazole core branched with different alkynyl donor groups has been characterized and tested in organic field-effect transistors (OFETs).     

DNA–affibody nanoparticle delivery system for cisplatin-based breast cancer chemotherapy

Cisplatin is the most widely used anticancer drug, but its side effects limit the maximum systemic dose. To circumvent the side effects, a DNA tetrahedron–affibody nanoparticle was prepared by combination of a DNA chain with cisplatin via interstrand crosslinks or adducts. Each nanocarrier can bind ∼68 molecules of cisplatin. This cisplatin nanoparticle exhibited high selectivity and inhibition for breast cancer HER2 overexpressing cells BT474 and lower toxicity in MCF-7 cells with low HER2 expression. The nano-drug inhibited the growth of BT474 cells by 94.57% at 512 nM (containing 33.3 μM cisplatin), which was higher than that of cisplatin (82.9%, 33.3 μM).

The novel nano-drug cisplatin-DNA tetrahedron-affibody has high specificity, high efficacy, and low toxicity for the treatment of HER2-overexpressing breast cancers.     

Strategy to design a smart photocleavable and pH sensitive chitosan based hydrogel through a novel crosslinker: a potential vehicle for controlled drug delivery

We report herein the synthesis of a novel photocleavable crosslinker, 4-formylphenyl 4-((4-formylphenoxy)methyl)-3-nitrobenzoate (CHO–ONB–CHO) and its joining with amine-based polysaccharides, viz. chitosan, resulting in the formation of a dual stimuli-responsive (ONB–chitosan) hydrogel having UV- and pH-responsive sites. The detailed mechanism for the formation of CHO–ONB–CHO and ONB–chitosan hydrogel is proposed. The (CHO–ONB–CHO) crosslinker was characterized using ¹H-NMR, LCMS and UV-visible spectroscopy. The dual responsive hydrogel is characterized by FTIR, SEM, XRD, DSC and TGA. The crosslinked hydrogel displayed mechanical robustness with a storage modulus of about 1741 pa. The pH-responsiveness of the hydrogel was studied via equilibrium swelling studies in various pH media at 37 °C. The photocleavable behavior of the crosslinker was observed in the UV-absorption range of 310–340 nm and the hydrogel exhibited maximum swelling at pH 5.7. The higher swelling of the hydrogel in acidic conditions and its photo-responsiveness can be exploited for the controlled, temporal and spatial release of therapeutic drugs at any inflammatory areas with acidic environments. It was observed that the hydrogel exhibited higher drug release at pH 5.7 than at pH 7.4.

We report the synthesis of a novel photocleavable crosslinker and its joining with amine-based polysachharides, viz. chitosan, resulting in the formation of a dual stimuli-responsive hydrogel having UV- and pH-responsive sites.     

Designing a high-performance smart drug delivery system for the synergetic co-absorption of DOX and EGCG on ZIF-8

Due to the extreme pore volume and valuable surface area, zeolitic imidazole frameworks (ZIFs) are promising vehicles that enhance the delivery of therapeutic agents to tissues. Furthermore, these nanoporous materials have high stability in the pH and temperature of the surrounding healthy cells (37 °C and pH = 7) and an exotic potential to deform in carcinogenic environment (T > 37 °C and pH ∼ 5.5), which make them perfect smart drug delivery vehicle candidates. In this work, a series of molecular dynamics (MD) and metadynamics simulations have been performed to gain molecular insight into the mechanisms involved in the process of co-loading of doxorubicin (DOX) and EpiGalloCatechin-3 Gallate (EGCG) on ZIF-8, which form a smart drug delivery system (SDDS). The obtained results revealed that DOX was adsorbed on the carrier mostly through electrostatic interactions (E_coul = ∼−1200 kJ mol⁻¹, E_tot = −1700 kJ mol⁻¹), and EGCG was stacked on ZIF-8 mainly via van der Waals interactions (E_L-J = ∼−600 kJ mol⁻¹, E_tot = ∼−1200 kJ mol⁻¹). It is worth mentioning that the drug–drug L-J interactions (E_L-J = ∼500 kJ mol⁻¹) were also important in the co-loading process. The insertion of DOX and EGCG as additive agents to the initial ZIF-8/EGCG and ZIF-8/DOX systems led to the enhancement of the drug–carrier pair interactions to about ∼−2300 kJ mol⁻¹ and ∼−2000 kJ mol⁻¹, respectively. This finding implied that the drug–drug interactions had a complementary role in the development of SDDS via ZIF-8. From the metadynamics simulation, it was found that the geometry of the drugs is a determining factor in an efficient co-loading SDDS.

Adsorption free energy of a molecule depends on where and how the molecule meets ZIF-8 surface.     

Gallic acid-functionalized graphene hydrogel as adsorbent for removal of chromium (iii) and organic dye pollutants from tannery wastewater

The pollution caused by tannery wastewater containing high concentrations of trivalent chromium ions [Cr(iii)] and organic dyes has severely restricted the sustainable development of the leather industry. To address this problem, a three-dimensional (3D) porous graphene-based hydrogel with good mechanical strength and large surface area was fabricated by self-assembly of graphene oxide (GO) sheets reduced and modified by gallic acid (GA) through π–π interactions. As an adsorbent, this GA-functionalized graphene hydrogel (GA-GH) can effectively capture Cr(iii) by coordination complexation between Cr(iii) and deprotonated carboxylic groups of GA at pH ∼ 4.0. Moreover, GA-GH could be easily regenerated by desorption of adsorbed Cr(iii) at pH 2.0 and maintained its high adsorption capacity after multiple adsorption–desorption cycles, which was also helpful for reusing desorbed Cr(iii) as tanning agent. In addition, compared with a graphene hydrogel (GH) without modification by GA, adsorption capacity of GA-GH for organic dye was significantly improved due to the enhanced π–π interactions between the GA-GH and aromatic dyes.

The formation process of gallic acid functionalized graphene hydrogel (GA-GH).     

The pH-triggered drug release and simultaneous carrier decomposition of effervescent SiO2–drug–Na2CO3 composite nanoparticles: to improve the antitumor activity of hydrophobic drugs

To achieve a better release effect of hydrophobic drugs and spontaneous nanocarrier disintegration by dissolution as well as the CO₂ production of Na₂CO₃ further, improving the therapeutic effect of hydrophobic drugs, and thereby avoiding the accumulation of the nanocarrier in vivo to produce organ toxicity, effervescent SiO₂–drug–Na₂CO₃ composite nanoparticles (ESNs) were prepared in this study using a tetraethyl orthosilicate hydrolysis method. Sodium carbonate was used as the effervescent disintegrant to respond to the acidic microenvironment of the tumor. The properties of ESNs were assessed and TEM images were taken to verify the self-disintegration characteristics of nanocarrier materials. The in vitro anticancer efficacy of ESNs was evaluated in human breast cancer MCF-7 cells. ESNs loaded with hydrophobic drugs were successfully constructed, and showed high entrapment efficiency and drug loading. The nanocarrier successfully achieved self-disintegration in a PBS environment of pH value at 5.0, and showed excellent antitumor effect in vitro. ESNs can effectively load hydrophobic drugs and achieve self-disintegration, while avoiding toxicity from the accumulation of the nanocarrier. These results suggest that ESNs are a promising drug delivery system capable of maximizing the anticancer therapeutic efficacy and minimizing the systemic toxicity.

Effervescent SiO₂–drug–Na₂CO₃ composite nanoparticles were prepared in this study using a tetraethyl orthosilicate hydrolysis method to achieve a better release effect of hydrophobic drugs and spontaneous nanocarrier disintegration by dissolution.