Fabrication of a dual pH-responsive and photothermal microcapsule pesticide delivery system for controlled release of pesticides.

BACKGROUND: The development of stimulus-responsive and photothermally controlled-release microcapsule pesticide delivery systems is a promising solution to enhance the effective utilization and minimize the excessive use of pesticides in agriculture. RESULTS: In this study, an AVM@CS@TA-Fe microcapsule pesticide delivery system was developed using avermectin as the model drug, chitosan and tannic acid as the wall materials, and tannic acid-Fe complex layer as the photothermal agent. The optical microscope, scanning electron microscope, transmission electron microscope, and Fourier-transform infrared spectroscope were used to characterize the prepared microcapsule. The slow-release, UV-shielding, photothermal performance, and nematicidal activity of the microcapsule were systematically investigated. The results showed that the system exhibited excellent pH-responsive and photothermal-sensitive performances. In addition, the UV-shielding performance of the delivery system was improved. The photothermal conversion efficiency (η) of the system under the irradiation of near-infrared (NIR) light was determined to be 14.18%. Moreover, the nematicidal activities of the system against pine wood nematode and Aphelenchoides besseyi were greatly increased under the irradiation of light-emitting diode (LED) simulated sunlight. CONCLUSION: The release of the pesticide-active substances in such a pesticide delivery system could be effectively regulated with the irradiation of NIR light or LED-simulated sunlight. Thus, the developed pesticide delivery system may have broad application prospects in modern agriculture fields. © 2022 Society of Chemical Industry.

Ceria-Containing Hybrid Multilayered Microcapsules for Enhanced Cellular Internalisation with High Radioprotection Efficiency.

Cerium oxide nanoparticles (nanoceria) are believed to be the most versatile nanozyme, showing great promise for biomedical applications. At the same time, the controlled intracellular delivery of nanoceria remains an unresolved problem. Here, we have demonstrated the radioprotective effect of polyelectrolyte microcapsules modified with cerium oxide nanoparticles, which provide controlled loading and intracellular release. The optimal (both safe and uptake efficient) concentrations of ceria-containing microcapsules for human mesenchymal stem cells range from 1:10 to 1:20 cell-to-capsules ratio. We have revealed the molecular mechanisms of nanoceria radioprotective action on mesenchymal stem cells by assessing the level of intracellular reactive oxygen species (ROS), as well as by a detailed 96-genes expression analysis, featuring genes responsible for oxidative stress, mitochondrial metabolism, apoptosis, inflammation etc. Hybrid ceria-containing microcapsules have been shown to provide an indirect genoprotective effect, reducing the number of cytogenetic damages in irradiated cells. These findings give new insight into cerium oxide nanoparticles' protective action for living beings against ionising radiation.

Preparation and performance of a BTDA-modified polyurea microcapsule for encapsulating avermectin.

A pesticide microcapsule was prepared by encapsulating avermectin (AVM) in a polyurea microcapsule via interfacial polymerization in acetic ether/water emulsion. The polyurea microcapsule was consisted of chitosan oligomer (CO) as the membrane material and diphenyl methane-4,4'-diisocyanate (MDI) as the crosslinker. A chemical modification was carried out by grafting a UV-absorbent, 3,3',4,4'-benzophenonetetracarboxylic dianhydride (BTDA), to CO before interfacial polymerization to enhance the UV-resistance of the microcapsule. The BTDA grafted CO (CO-BTDA) and the AVM microcapsules were characterized by a variety of instrumental techniques, including NMR, FTIR, UV-vis, GPC-LS, DLS, SEM and TEM. The in vitro release test showed that the polyurea microcapsule maintained the sustained release of AVM for a longer period (up to 120 h) in comparison with the commercial AVM formulations (within 24 h). The photodegradation test revealed that the polyurea microcapsule significantly reduced the AVM degradation and extended the half-life of AVM from 4.16 h to 9.43 h. The AVM degradation was further reduced by using the BTDA-modified polyurea microcapsule. The corresponding half-life was extended up to 17.33 h and can be mediated by changing the mass ratio of BTDA: CO during the synthesis of CO-BTDA. The use of polyurea microcapsule did not raise a concern about pesticide residue as no AVM was detected after the photodegradation test. In addition, the polyurea microcapsule itself was subject to degradation under sunlight exposure, which reduced its residue in the environment.

Application of Gamma Radiation on Hard Gelatin Capsules as Sterilization Technique and Its Consequences on the Chemical Structure of the Material.

Hard capsules are made from gelatin, an organic polymer obtained through the hydrolysis of collagen present in animal tissues. Gelatin can be degraded by microorganisms and some strategies can be used to control contaminating micro-organisms. Gamma irradiation is considered as an effective sterilization method; however, its application can alter the chemical structure of the irradiated product. Samples of hard gelatin capsules were irradiated at doses of 5, 15, and 25 kGy at room temperature. The characterizations of the physical and chemical effects were evaluated by scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffractometry, and differential scanning calorimetry techniques. Furthermore, hard gelatin capsule samples were dissolved and inoculated with Bacillus subtilis, a Gram-positive spore-forming bacterium, to evaluate the effect of gamma ray radiation on bacterial counts. The results showed that gamma radiation did not interfere on physical parameters of the capsule, such as moisture content, mass, body and cap length, and disintegration time. Nevertheless, differential scanning calorimetry results demonstrated changes in the glass transition temperature, indicating the formation of crosslinking in irradiated capsules. It was observed that there were significant reductions on the inoculated bacterial population starting from the lowest irradiation dose and there was no detection of bacterial growth from the 15 kGy dose, while in the non-irradiated samples were found with 104 CFU mL-1 of bacteria. Therefore, this work concludes that the gamma radiation is effective on the reduction of the microbial population, cause discrete physical-chemical alterations, and could be used as a hard capsule sterilization technique.

Synthesis and Characterization of Stimuli-Responsive Poly(2-dimethylamino-ethylmethacrylate)-Grafted Chitosan Microcapsule for Controlled Pyraclostrobin Release.

Controllable pesticide release in response to environmental stimuli is highly desirable for better efficacy and fewer adverse effects. Combining the merits of natural and synthetic polymers, pH and temperature dual-responsive chitosan copolymer (CS-g-PDMAEMA) was facilely prepared through free radical graft copolymerization with 2-(dimethylamino) ethyl 2-methacrylate (DMAEMA) as the vinyl monomer. An emulsion chemical cross-linking method was used to expediently fabricate pyraclostrobin microcapsules in situ entrapping the pesticide. The loading content and encapsulation efficiency were 18.79% and 64.51%, respectively. The pyraclostrobin-loaded microcapsules showed pH-and thermo responsive release. Microcapsulation can address the inherent limitation of pyraclostrobin that is photo unstable and highly toxic on aquatic organisms. Compared to free pyraclostrobin, microcapsulation could dramatically improve its photostability under ultraviolet light irradiation. Lower acute toxicity against zebra fish on the first day and gradually similar toxicity over time with that of pyraclostrobin technical concentrate were in accordance with the release profiles of pyraclostrobin microcapsules. This stimuli-responsive pesticide delivery system may find promising application potential in sustainable plant protection.

Orthogonal near-infrared upconversion co-regulated site-specific O2 delivery and photodynamic therapy for hypoxia tumor by using red blood cell microcarriers.

Pre-existing hypoxia in tumors can result in an inadequate oxygen supply during photodynamic therapy (PDT), which in turn hampers photodynamic efficacy. To overcome this problem, we developed an orthogonal near-infrared upconversion controlled red blood cell (RBC) microcarriers to selectively deliver O2 in hypoxia area. Moreover, this RBC microcarriers are able to overcome a series of complex biological barriers which include transporting across the inflamed endothelium, evading mononuclear phagocyte system, reducing reticuloendothelial system uptake. Based on these abilities, RBC microcarriers have efficient tumors accumulation and are capable of delivery a large amount of O2 for PDT under near-infrared (NIR) irradiation to realize effective solid tumor eradication.

Treatment of Parkinson's disease in rats by Nrf2 transfection using MRI-guided focused ultrasound delivery of nanomicrobubbles.

Parkinson's disease (PD) is a very common neurological disorder. However, effective therapy is lacking. Although the blood-brain-barrier (BBB) protects the brain, it prevents the delivery of about 90% of drugs and nucleotides into the brain, thereby hindering the development of gene therapy for PD. Magnetic resonance imaging (MRI)-guided focused ultrasound delivery of microbubbles enhances the delivery of gene therapy vectors across the BBB and improves transfection efficiency. In the present study, we delivered nuclear factor E2-related factor 2 (Nrf2, NFE2L2) contained in nanomicrobubbles into the substantia nigra of PD rats by MRI-guided focused ultrasound, and we examined the effect of Nrf2 over-expression in this animal model of PD. The rat model of PD was established by injecting 6-OHDA in the right substantia nigra stereotactically. Plasmids (pDC315 or pDC315/Nrf2) were loaded onto nanomicrobubbles, and then injected through the tail vein with the assistance of MRI-guided focused ultrasound. MRI-guided focused ultrasound delivery of nanomicrobubbles increased gene transfection efficiency. Furthermore, Nrf2 gene transfection reduced reactive oxygen species levels, thereby protecting neurons in the target region.

Conducting polymers with defined micro- or nanostructures for drug delivery.

Conducting polymers (CPs) are redox active materials with tunable electronic and physical properties. The charge of the CP backbone can be manipulated through redox processes, with accompanied movement of ions into and out of the polymer to maintain electrostatic neutrality. CPs with defined micro- or nanostructures have greatly enhanced surface areas, compared to conventionally prepared CPs. The resulting high surface area interface between polymer and liquid media facilities ion exchange and can lead to larger and more rapid responses to redox cycling. CP systems are maturing as platforms for electrically tunable drug delivery. CPs with defined micro- or nanostructures offer the ability to increase the amount of drug that can be delivered whilst enabling systems to be finely tuned to control the extent and rate of drug release. In this review, fabrication approaches to achieve CPs with micro- or nanostructure are outlined followed by a detailed review and discussion of recent advances in the application of the materials for drug delivery.

Folate-conjugated gene-carrying microbubbles with focused ultrasound for concurrent blood-brain barrier opening and local gene delivery.

Previous studies have demonstrated that circulating DNA-encapsulated microbubbles (MBs) combined with focused ultrasound (FUS) can be used for local blood-brain barrier (BBB) opening and gene delivery. However, few studies focused on how to increase the efficiency of gene delivery to brain tumors after the released gene penetrating the BBB. Here, we proposed the use of folate-conjugated DNA-loaded cationic MBs (FCMBs). When combined with FUS as a trigger for BBB opening, FCMBs were converted into nanometer-sized vesicles that were transported to the brain parenchyma. The FCMBs can selectively aggregate around tumor cells that overexpressed the folate receptor, thus enhancing gene delivery via folate-stimulated endocytosis. Our results confirmed that FCMBs can carry DNA on the surface of the MB shell and have good targeting ability on C6 glioma cells. In addition, the optimized FUS parameters for FCMBs-enhanced gene delivery were confirmed by cell experiments (center frequency = 1 MHz; acoustic pressure = 700 kPa; pulse repetition frequency = 5 Hz; cycle number = 10000; exposure time = 1 min; FCMBs concentration = 4 × 10(7) MB/mL). In vivo data also indicated that FCMBs show better gene transfection efficiency than MBs without folate conjugation and the traditional approach of directly injecting the gene. This study described our novel development of multifunctional MBs for FUS-triggered gene delivery/therapy.

Microcapsules and 3D customizable shelled microenvironments from laser direct-written microbeads.

Microcapsules are shelled 3D microenvironments, with a liquid core. These core-shelled structures enable cell-cell contact, cellular proliferation and aggregation within the capsule, and can be utilized for controlled release of encapsulated contents. Traditional microcapsule fabrication methods provide limited control of capsule size, and are unable to control capsule placement. To overcome these limitations, we demonstrate size and spatial control of poly-l-lysine and chitosan microcapsules, using laser direct-write (LDW) printing, and subsequent processing, of alginate microbeads. Additionally, microbeads were used as volume pixels (voxels) to form continuous 3D hydrogel structures, which were processed like capsules, to form custom shelled aqueous-core 3D structures of prescribed geometry; such as strands, rings, and bifurcations. Heterogeneous structures were also created with controlled initial locations of different cell types, to demonstrate the ability to prescribe cell signaling (heterotypic and homotypic) in co-culture conditions. Herein, we demonstrate LDW's ability to fabricate intricate 3D structures, essentially with "printed macroporosity," and to precisely control structural composition by bottom-up fabrication in a bead-by-bead manner. The structural and compositional control afforded by this process enables the creation of a wide range of new constructs, with many potential applications in tissue engineering and regenerative medicine. Biotechnol. Bioeng. 2016;113: 2264-2274. © 2016 Wiley Periodicals, Inc.

Interfacial Rheological Properties of Contrast Microbubble Targestar P as a Function of Ambient Pressure.

In this Technical Note, we determine the interfacial rheological parameters of the encapsulation of the contrast agent Targestar P using ultrasound attenuation. The characteristic parameters are obtained according to two interfacial rheological models. The properties-surface dilatational elasticity (0.09 ± 0.01 N/m) and surface dilatational viscosity (8 ± 0.1E-9 N·s/m)-are found to be of similar magnitude for both models. Contrast microbubbles experience different ambient pressure in different organs. We also measure these parameters as functions of ambient pressure using attenuation measured at different overpressures (0, 100 and 200 mm Hg). For each value of ambient hydrostatic pressure, we determine the rheological properties, accounting for changes in the size distribution caused by the pressure change. We discuss different models of size distribution change under overpressure: pure adiabatic compression or gas exchange with surrounding medium. The dilatational surface elasticity and viscosity are found to increase with increasing ambient pressure.

Fluid Viscosity Affects the Fragmentation and Inertial Cavitation Threshold of Lipid-Encapsulated Microbubbles.

Ultrasound and microbubble optimization studies for therapeutic applications are often conducted in water/saline, with a fluid viscosity of 1 cP. In an in vivo context, microbubbles are situated in blood, a more viscous fluid (∼4 cP). In this study, ultrahigh-speed microscopy and passive cavitation approaches were employed to investigate the effect of fluid viscosity on microbubble behavior at 1 MHz subject to high pressures (0.25-2 MPa). The propensity for individual microbubble (n = 220) fragmentation was found to significantly decrease in 4-cP fluid compared with 1-cP fluid, despite achieving similar maximum radial excursions. Microbubble populations diluted in 4-cP fluid exhibited decreased wideband emissions (up to 10.2 times), and increasingly distinct harmonic emission peaks (e.g., ultraharmonic) with increasing pressure, compared with those in 1-cP fluid. These results suggest that in vitro studies should consider an evaluation using physiologic viscosity perfusate before transitioning to in vivo evaluations.

Ultrasonically Assisted Polysaccharide Microcontainers for Delivery of Lipophilic Antitumor Drugs: Preparation and in Vitro Evaluation.

High toxicity, poor selectivity, and severe side effects are major drawbacks of anticancer drugs. Various drug delivery systems could be proposed to overcome these limitations. The aim of this study was to fabricate polysaccharide microcontainers (MCs) loaded with thymoquinone (TQ) by a one-step ultrasonication technique and to study their cellular uptake and cytotoxicity in vitro. Two MC fractions with a mean size of 500 nm (MC-0.5) and 2 µM (MC-2) were prepared and characterized. Uptake of the MCs by mouse melanoma M-3 cells was evaluated in both 2D (monolayer culture) and 3D (multicellular tumor spheroids) models by confocal microscopy, flow cytometry, and fluorimetry. The higher cytotoxicity of the TQ-MC-0.5 sample than the TQ-MC-2 fraction was in good correlation with higher MC-0.5 accumulation in the cells. The MC-0.5 beads were more promising than the MC-2 particles because of a higher cellular uptake in both 2D and 3D models, an enhanced antitumor effect, and a lower nonspecific toxicity.

Evaluation of the potential of doxorubicin loaded microbubbles as a theranostic modality using a murine tumor model.

In this study, a novel phospholipid-based microbubble formulation containing doxorubicin and perfluoropropane gas (DLMB) was developed. The DLMBs were prepared by mechanical agitation of a phospholipid dispersion in the presence of perfluoropropane (PFP) gas. An anionic phospholipid, distearoyl phosphatidylglycerol (DSPG) was selected to load doxorubicin in the microbubbles by means of electrostatic interaction. The particle size, zeta potential, echogenicity and stability of the DLMBs were measured. Drug loading was ⩾ 92%. The potential of the DLMBs for use as a theranostic modality was evaluated in tumor bearing mice. Gas chromatography analysis of PFP showed significant enhancement of PFP retention when doxorubicin was used at concentrations of 10-82% equivalent to DSPG. The inhibitory effects on the proliferation of B16BL6 melanoma murine cells in vitro were enhanced using a combination of ultrasound (US) irradiation and DLMBs. Moreover, in vivo DLMBs in combination with (US) irradiation significantly inhibited the growth of B16BL6 melanoma tumor in mice. Additionally, US echo imaging showed high contrast enhancement of the DLMBs in the tumor vasculature. These results suggest that DLMBs could serve as US triggered carriers of doxorubicin as well as tumor imaging agents in cancer therapy.

Targeted concurrent chemoradiotherapy, by using improved microcapsules that release carboplatin in response to radiation, improves detectability by computed tomography as well as antitumor activity while reducing adverse effect in vivo.

PURPOSE: The effect of alginate-hyaluronate microcapsules that release carboplatin in response to radiation was improved by adding ascorbic acid (AA). MATERIALS AND METHODS: Four measures of the effectiveness of the microcapsules were evaluated: 1) release of carboplatin in response to radiation in vitro and in vivo; 2) detectability of their accumulation by computed tomography (CT) in vivo; 3) enhancement of antitumor effects in vivo; and 4) reduction of adverse effects in vivo. RESULTS: There were significant increases in the rupture of microcapsules by adding AA in vitro. Subcutaneously injected microcapsules around the tumor could be detected by using CT and the alteration of CT-values correlated with the accumulation of the microcapsules. Those microcapsules released carboplatin and resulted in synergistic antitumor effect with concomitant radiation. With the encapsulation of carboplatin, chemotherapeutic effects were still observed two weeks after treatment. However, addition of AA did not result in increased antitumor effect in vivo. A reduction in adverse effects was observed with the encapsulation of carboplatin, through localization of carboplatin around the tumor. CONCLUSION: Addition of AA to the materials of microcapsules did not result in increasing antitumor effect. However encapsulation of carboplatin will be useful as a clinical cancer-therapy option.

Delivery of molecules to the lymph node via lymphatic vessels using ultrasound and nano/microbubbles.

Lymph node (LN) dissection is the primary option for head and neck cancer when imaging modalities and biopsy confirm metastasis to the sentinel LN. However, there are no effective alternative treatments to dissection for LN metastasis. Here, we describe a novel drug delivery system combining nano/microbubbles (NMBs) with ultrasound (US) that exhibits considerable potential for the delivery of exogenous molecules into LNs through the lymphatic vessels. A solution containing fluorophores (as a model of a therapeutic molecule) and NMBs was injected into the subiliac LNs of MXH10/Mo-lpr/lpr mice, which develop systemic swelling of LNs (up to 13 mm in diameter, similar to human LNs). It was found that the NMBs were delivered to the entire area of the proper axillary LN (proper-ALN) via the lymphatic channels and that these were retained there for more than 8 min. Furthermore, exposure to US in the presence of NMBs enhanced the delivery of fluorophores into the lymphocytes near the lymphatic channels, compared with exposure to US in the absence of NMBs. It is proposed that a system using US and NMBs to deliver therapeutic drugs via lymphatic vessels can serve as a new treatment method for LN metastasis.

Sonochemical fabrication of dual-targeted redox-responsive smart microcarriers.

In the present study, the molecular and magnetic dual-targeted redox-responsive folic acid-cysteine-Fe3O4 microcapsules (FA-Cys-Fe3O4 MCs) have been synthesized via the sonochemical technique, and targeting molecule (folic acid) and Fe3O4 magnetic nanoparticles are introduced into the microcapsule shells successfully. The obtained FA-Cys-Fe3O4 MCs show excellent magnetic responsive ability by the oriented motion under an external magnetic field. The hydrophobic fluorescent dye (Coumarin 6) is successfully loaded into the FA-Cys-Fe3O4 MCs, demonstrating that it could be also easily realized to encapsulate hydrophobic drugs into the FA-Cys-Fe3O4 MCs when the drugs are dispersed into the oil phase before sonication. Cellular uptake demonstrates that FA-Cys-Fe3O4 MCs could target selectively the cells via folate-receptor-mediated endocytosis. Moreover, the FA-Cys-Fe3O4 MCs show their potential ability to be an attractive carrier for drug controlled release owing to the redox responsiveness of the disulfide in the microcapsule shells.

An IVUS transducer for microbubble therapies.

There is interest in examining the potential of modified intravascular ultrasound (IVUS) catheters to facilitate dual diagnostic and therapeutic roles using ultrasound plus microbubbles for localized drug delivery to the vessel wall. The goal of this study was to design, prototype, and validate an IVUS transducer for microbubble-based drug delivery. A 1-D acoustic radiation force model and finite element analysis guided the design of a 1.5-MHz IVUS transducer. Using the IVUS transducer, biotinylated microbubbles were displaced in water and bovine whole blood to the streptavidin-coated wall of a flow phantom by a 1.5-MHz center frequency, peak negative pressure = 70 kPa pulse with varying pulse repetition frequency (PRF) while monitoring microbubble adhesion with ultrasound. A fit was applied to the RF data to extract a time constant (τ). As PRF was increased in water, the time constant decreased (τ = 32.6 s, 1 kHz vs. τ = 8.2 s, 6 kHz), whereas in bovine whole blood an adhesion-no adhesion transition was found for PRFs ≥ 8 kHz. Finally, a fluorophore was delivered to an ex vivo swine artery using microbubbles and the IVUS transducer, resulting in a 6.6-fold increase in fluorescence. These results indicate the importance of PRF (or duty factor) for IVUS acoustic radiation force microbubble displacement and the potential for IVUS and microbubbles to provide localized drug delivery.

Albumin acts like transforming growth factor ß1 in microbubble-based drug delivery.

Unlike lipid-shelled microbubbles (MBs), albumin-shelled microbubbles (MBs) have not been reported to be actively targeted to cells without the assistance of antibodies. Recent studies indicate that the albumin molecule is similar to transforming growth factor ß (TGF-ß) both structurally and functionally. The TGF-ß superfamily is important during early tumor outgrowth, with an elevated TGF-ß being tumor suppressive; at later stages, this switches to malignant conversion and progression, including breast cancer. TGF-ß receptors I and II play crucial roles in both the binding and endocytosis of albumin. However, until now, no specific albumin receptor has been found. On the basis of the above-mentioned information, we hypothesized that non-antibody-conjugated albumin-shelled MBs can be used to deliver drugs to breast cancer cells. We also studied the possible roles of TGF-ß1 and radiation force in the behavior of cells and albumin-shelled MBs. The results indicate that albumin-shelled MBs loaded with paclitaxel (PTX) induce breast cancer cell apoptosis without the specific targeting produced by an antibody. Applying either an acoustic radiation force or cavitation alone to cells with PTX-loaded albumin MBs increased the apoptosis rate to 23.2% and 26.3% (p < 0.05), respectively. We also found that albumin-shelled MBs can enter MDA-MB-231 breast cancer cells and remain there for at least 24 h, even in the presence of PTX loading. Confocal micrographs revealed that 70.5% of the breast cancer cells took up albumin-shelled MBs spontaneously after 1 d of incubation. Applying an acoustic radiation force further increased the percentage to 91.9% in our experiments. However, this process could be blocked by TGF-ß1, even with subsequent exposure to the radiation force. From these results, we conclude that TGF-ß1 receptors are involved in the endocytotic process by which albumin-shelled MBs enter breast cancer cells. The acoustic radiation force increases the contact rate between albumin-shelled MBs and tumor cells. Combining a radiation force and cavitation yields an apoptosis rate of 31.3%. This in vitro study found that non-antibody-conjugated albumin-shelled MBs provide a useful method of drug delivery. Further in vivo studies of the roles of albumin MBs and TGF-ß in different stages of cancer are necessary.

Near-infrared femtosecond laser-triggered nanoperforation of hollow microcapsules.

Fabrication of a nanopore in a hollow microcapsule was demonstrated using near-infrared femtosecond laser irradiation. The shape of the irradiated microcapsules was kept spherical except for a pore in the shell owing to the nonthermal processing by a femtosecond laser. The simulation results for the near-field and far-field scattering around a microcapsule revealed that highly-enhanced optical intensity can be generated at a spot on the shell of a microcapsule, which would in turn contribute to localized ablation. To the best of our knowledge, this is the first demonstration of the nanoperforation of transparent hollow microcapsules by a near-infrared laser without any doping with absorbing metals or dyes that may cause cell toxicity. The presented method is a promising approach for safer drug delivery and the controlled release of therapeutic drugs.