Good Photothermal Conversion Research Articles

Self-actuated biomimetic nanocomposites for photothermal therapy and PD-L1 immunosuppression.

Biomimetic nanocomposites are widely used in the biomedical field because they can effectively solve the problems existing in the current cancer treatment by realizing multi-mode collaborative treatment. In this study, we designed and synthesized a multifunctional therapeutic platform (PB/PM/HRP/Apt) with unique working mechanism and good tumor treatment effect. Prussian blue nanoparticles (PBs) with good photothermal conversion efficiency were used as nuclei and coated with platelet membrane (PM). The ability of platelets (PLTs) to specifically target cancer cells and inflammatory sites can effectively enhance PB accumulation at tumor sites. The surface of the synthesized nanocomposites was modified with horseradish peroxidase (HRP) to enhance the deep penetration of the nanocomposites in cancer cells. In addition, PD-L1 aptamer and 4T1 cell aptamer AS1411 were modified on the nanocomposite to achieve immunotherapy and enhance targeting. The particle size, UV absorption spectrum and Zeta potential of the biomimetic nanocomposite were determined by transmission electron microscope (TEM), Ultraviolet-visible (UV-Vis) spectrophotometer and nano-particle size meter, and the successful preparation was proved. In addition, the biomimetic nanocomposites were proved to have good photothermal properties by infrared thermography. The cytotoxicity test showed that it had a good killing ability of cancer cells. Finally, thermal imaging, tumor volume detection, immune factor detection and Haematoxilin-Eosin (HE) staining of mice showed that the biomimetic nanocomposites had good anti-tumor effect and could trigger immune response in vivo. Therefore, this biomimetic nanoplatform as a promising therapeutic strategy provides new inspiration for the current diagnosis and treatment of cancer.

The enhanced photocatalytic and photothermal effects of Ti3C2 Mxene quantum dot/macroscopic porous graphitic carbon nitride heterojunction for Hydrogen Production

A new heterostructure between Ti3C2 MXene quantum dot and 3D macroscopic porous graphitic carbon nitride (PGCN) was successfully obtained by integrating Ti3C2 quantum dots onto porous graphitized carbon nitride (Ti3C2QDs/PGCN) using in situ electrostatic self-assembly techniques. The photocatalytic H2 evolution rate of optimized 5.5 wt% Ti3C2 QD/PGCN composites is nearly 15.24 and 3.53 times higher than pristine CN, and PGCN, respectively. Ti3C2 quantum dots can significantly enhance the hydrogen production activity of PGCN. In addition, their good photothermal conversion ability accelerates the overall reaction process and enhances the light absorption and carrier density. Furthermore, to elucidate the photocatalytic mechanism, a series of tests involving electron spin resonance (ESR) and density functional theory (DFT) calculations were performed. The results confirmed that the Schottky barrier between PGCN and Ti3C2 QD can effectively promote spatial charge separation and significantly improve the photocatalytic performance. This work provides a new approach for the construction of photocatalytic systems and the application of MXene QD.

Small-size Ti3C2Tx MXene nanosheets coated with metal-polyphenol nanodots for enhanced cancer photothermal therapy and anti-inflammation.

As a controllable, simple method with few side effects, near-infrared (NIR) light-based photothermal therapy (PTT) has been proven an effective cancer therapeutic approach. However, PTT-induced inflammation is a potential negative factor. And the overexpressed heat shock proteins (HSPs) by cancer cells can protect them from hyperthermia during PTT. In this work, small-size Ti3C2Tx MXene nanosheets with high photothermal conversion efficiency in the region of NIR, high cargo loading capability and good free radical scavenging capability were chosen for cancer PTT and anti-inflammation. And (-)-epigallocatechin gallate (EGCG) was applied to form EGCG/Fe metal-polyphenol nanodots on the nanosheets. EGCG being released in acid cancer cells could reduce the expression of HSPs and could be used for anti-inflammation. As a result, the complex nanosheets named MXene@EGCG could achieve enhanced cancer PTT and be anti-inflammatory. Both in vitro and in vivo studies proved the good photothermal ability of MXene@EGCG and demonstrated that it could inhibit the expression of HSPs in tumor cells and relieve PTT-induced inflammation. Therefore, the nanosheets show good results in tumor ablation with a low level of inflammation, which provides another possibility for cancer therapy. STATEMENT OF SIGNIFICANCE: Photothermal therapy (PTT)-induced inflammation plays an essential role in some important stages of tumor development and is unfavorable for cancer treatment. And hyperthermia leads to the overexpression of heat shock proteins (HSPs) in cancer cells, which limits the therapeutic effect of PTT. Therefore, we coated small-size Ti3C2Tx MXene nanosheets with (-)-epigallocatechin gallate (EGCG)/Fe metal-polyphenol nanodots and named them as MXene@EGCG. This system shows a good photothermal conversion efficiency at 808 nm. And it can release EGCG in cancer cells to inhibit the expression of HSPs, thus achieving an enhanced cancer PTT. Both MXene and EGCG can also diminish the PTT-trigged inflammation. Both in vitro and in vivo studies prove the good anti-cancer PTT effect and anti-inflammation capability of MXene@EGCG.

Plasmon Driven Nanocrystal Transformation by Aluminum Nano-Islands with an Alumina Layer.

The plasmonic photothermal effects of metal nanostructures have recently become a new priority of studies in the field of nano-optics. Controllable plasmonic nanostructures with a wide range of responses are crucial for effective photothermal effects and their applications. In this work, self-assembled aluminum nano-islands (Al NIs) with a thin alumina layer are designed as a plasmonic photothermal structure to achieve nanocrystal transformation via multi-wavelength excitation. The plasmonic photothermal effects can be controlled by the thickness of the Al2O3 and the intensity and wavelength of the laser illumination. In addition, Al NIs with an alumina layer have good photothermal conversion efficiency even in low temperature environments, and the efficiency will not decline significantly after storage in air for 3 months. Such an inexpensive Al/Al2O3 structure with a multi-wavelength response provides an efficient platform for rapid nanocrystal transformation and a potential application for the wide-band absorption of solar energy.

Engineering nanofusiform Iron-doped polydiaminopyridine boost intratumoral penetration for immunogenic cell Death-mediated synergistic Photothermal/Chemo therapy

Photothermal therapy (PTT) featured the advantages of convenient operation, high selectivity and little side effects has been as a non-invasive and promising treatment that converts near infrared light into heat energy through photothermal agents, which however is also trouble with limited penetration depth of near-infrared light, low treatment efficiency and et.al. Considering this situation, we synthesized iron-doped poly (2, 6-diaminopyridine) nanoparticles (FDAP NPs) with fusiform morphology by one-step oxidative polymerization of Fe3+. To improve therapeutic outcome, the chemotherapeutic drug doxorubicin (DOX) was further decorated on the fusiform surface by hydrophobic interaction to get the expectant FDAP@DOX nanosystem. The collaborative design endowed FDAP@DOX with good photothermal conversion rate, which could convert light energy into heat energy under the irradiation of 808 nm wavelength laser, and then further increased the temperature of the tumor site and leaded to strong immunogenic cell death (ICD) and tumor cell apoptosis. Meanwhile, the increase of temperature also promoted the release of superficial DOX, realizing the synergistic therapeutic modalities of photothermal/chemo therapy and making the tumor weight losing more thorough in 4T1 breast tumor animal model. Thus, this study shows a facile but effective idea for the construction of multimodal therapy-based integrated nanomedicine, and offers a service for the field of photothermal/chemo tumor therapy.

A New Urokinase Plasminogen Activator Receptor‐Targeted Near‐Infrared Fluorescence (NIR) Probe for Glioma Imaging

AbstractA new fluorescent imaging probe indocyanine green‐VC (ICG‐VC) in the second near‐infrared window (NIR‐II) was fabricated based on the urokinase‐type plasminogen activator receptor (uPAR) targeted polypeptide VC (VSNKYFSNIHWGC). The relative quantum yield (ΦF)was 0.34 %. The tail of its fluorescence emission wavelength exceeded 1000 nm with excellent photostability. In vitro cell analysis, MTT results indicated the high biocompatibility of ICG‐VC with U87MG cells. ICG‐VC showed good photothermal conversion behavior and photothermal stability.In vivo NIR‐II fluorescence imaging, ICG‐VC exhibited high spatiotemporal resolution in the lymphatic vessels with a high resolution of 717 μm and signal‐to‐noise ratio of 4.36, and displayed an excellent U87MG tumor uptake within 4 h, which reached the maximum at 8 h with a signal‐to‐noise ratio of 5.32.

Injectable nano-composite hydrogels based on hyaluronic acid-chitosan derivatives for simultaneous photothermal-chemo therapy of cancer with anti-inflammatory capacity

Nowadays, the photothermal therapy (PTT) has received widespread attention and research by rapidly killing tumors with local high temperature. However, due to the irregular edges of tumor and the blurred boundary between normal and necrotic tissues, the desirable treatment cannot be achieved by the single PTT, and excessive heat will cause serious inflammation in local tissues. Herein, an injectable composite hydrogel is prepared by the oxidized hyaluronic acid (OHA) and hydroxypropyl chitosan (HPCS) via the imine bonds, which is employed as the delivery substrate for functional substances. In the gel medium, the mesoporous polydopamine (MPDA) nanoparticles are incorporated as the high efficiency photothermal agent and a reservoir of DOX, which can achieve the good photothermal conversion performance and pulsed drug release. Besides, the addition of the curcumin-cyclodextrin host-guest inclusion complex (CUR@NH2-CD) in the composite hydrogel could reduce the inflammation caused by PTT. The composite hydrogel shows favorable the Hepa1–6 tumor inhibition in vivo by virtue of the comprehensive effect of the admired photothermal efficacy of MPDA, chemotherapy of DOX and anti-inflammatory of CUR. It can be predicted that the composite hydrogel has a broad prospect in the field of comprehensive therapy for tumor.

Fractal Growth of Quasi Two-Dimensional Copper Dendrites by Template-free Electrodeposition

Fractal dendrites are extensively observed in industry, especially in the electrochemical deposition process. The fractal dendrite electrodeposition behavior of quasi-two-dimensional Cu (Q2D-Cu) metal based on the wire is examined via direct electrodeposition using a thin layer reactor. Here, to explain the fractal growth mechanism, the directional migration and random walking of ions are introduced in the traditional diffusion-limited aggregation model, and fractal patterns consistent with the experimental results are successfully simulated. In addition, the Cu fractal dendrite structure is finely adjusted by varying electrodeposition conditions, demonstrating its great potential for further optimization. The CuO/Q2D-Cu fractal dendrite photothermal device fabricated through in situ assembly of CuO nanowires on Cu fractal dendrite has good photothermal conversion ability. Therefore, metal fractal dendrites, which are considered harmful in the electroplating industry, have application prospects in the photothermal field.

Highly Sensitive Flexible Thermal Sensors Based on a Kind of MXene/DES Inks

Extremely hot weather has emerged more and more frequently in recent years, which has caused some serious disasters such as forest fires, heat-related illnesses, machine breakdowns, and so on. Flexible thermal sensors will be an efficient solution to achieve large area coverage of thermal alarm systems, due to their merits of low cost, portability, and easy processing. In the preparation of flexible sensors, the printing method stands out for its efficient and inexpensive characteristics. In this work, just by combining the high-NIR photothermal conversion material MXene (Ti3C2Tx) and thermosensitive substance metal salt (FeCl3)-based deep eutectic solvents (DES), conductive thermally sensitive inks were prepared. The MXene/DES-based ink with a suitable viscosity can be smoothly screen-printed on A4 paper. The as-prepared sensors can quickly generate heat even up to over 200 °C and simultaneously respond to the temperature change under near-infrared light (NIR, 808 nm). The type of metal salt can be replaced with other common metals, such as AlCl3, ZnCl2, SnCl2, and CuCl2, and some of them also presented good photothermal conversion ability. These inks are easy to synthesize, and the printed sensors are portable and easy to integrate, which make them a good candidate for building flexible thermal alarm systems.

Indocyanine green-/TLR7 agonist-constructed thermosensitive liposome for low-temperature PTT induced synergistic immunotherapy of colorectal cancer

Colorectal cancer (CRC) is a lethal malignancy with a high mortality rate due to its low immunogenicity, the strong immunosuppressive milieu and poor drug permeability. To overcome these obstacles, a cascade synergistic nanosystem (denoted as R837/ICG@Lip) was developed via self-assembly of heater indocyanine green (ICG) and toll-like receptor-7 agonist imiquimod (R837) into thermosensitive liposome for simultaneous induction of immunogenic cell death (ICD) and reversing of suppressive tumor microenvironment. The obtained nanoparticles exhibited NIR-triggered drug release, good photothermal conversion efficiency and phototoxicity towards CT26 colorectal cancer cells. In vivo results reveal that the R837/ICG@Lip could be effectively accumulated in CT26 subcutaneous tumors and the draining lymph nodes. More importantly, R837/ICG@Lip-mediated low-temperature photothermal therapy triggers ICD, promotes the maturation of host dendritic cells (DCs), and subsequently amplifies adaptive antitumor T-cell responses, resulting in ‘Cold to Hot’ transition. Besides directly affecting immune cells, the secretion of some immune-related cytokines further indirectly boosted anti-cancer immunity. After combining with the indoleamine 2,3-dioxygenase (IDO) inhibitor, the systemic antitumor immune response was further augmented, achieving best tumor inhibition effects. Thus, low-temperature mediated photoimmunotherapy targeting multiple antitumor immune pathways boost synergistic antitumor immunity of tolerance tumors.

Smart free-standing film force-assembled by Ti3C2Tx/CNC with high sensitivity to humidity and near-infrared light

Smart films that can specifically recognize the outer surrounding change and make rapid motion behavior, have presented their potential application in composing intelligent actuators. Herein, we have prepared a hydrophilic free-standing film with the nacre-like layered and directional aligned structure by vacuum-filtering the mixed suspension of Ti3C2Tx nanosheets and cellulose nanocrystal (CNC). Because of the axial Young’s modulus from the oriented arrangement of CNC and Ti3C2Tx, the assembled hybrid film can achieve fast and directed humidity-driven performance, and obtain a specific bending angle by controlling the asymmetric humidity value. Besides, the introduction of CNC also increased the surficial roughness of the hybrid film compared to the pure Ti3C2Tx film, which lengthened the light propagation path. Based on the good photothermal conversion ability of Ti3C2Tx nanosheets around the NIR region, the hybrid film presented ultra-high NIR conversing efficiency that can rapidly heat up to 178.2 °C only under the NIR (808 nm) power of 0.45 W/cm2. Therefore, by depositing thermochromism materials with different color change points, the composited film can realize visual temperature detection. This TC/CNC film with the ability of humidity and NIR sensing will satisfy the further demand for designing smart equipment.

Bilayer bamboo for photothermal trap and large-scale anti-icing

Ice buildup is a safety hazard for infrastructure, transportation and power lines. However, superhydrophobic anti-icing surfaces as well as traditional mechanical and chemical means can hardly coordinate the high anti-icing efficiency with the durable reusability, energy expenditure or environmental impact. Herein, a sustainable, low-cost and dual-action bilayer bamboo (BLB) sheet is developed by bamboo carbonization and surface hydrogel coating. This BLB laminate consisting of a carbonized bamboo (CB) substrate as photo-absorber and thermal insulator and a gel layer as absorber and heat spreader exhibit highly efficient anti-freezing and de-icing performances by converting solar illumination to heat and ion-specifically inhibiting heterogeneous ice nucleation (HIN). This BLB shows remarkable comprehensive performances of low ice adhesion (τice ≈ 0 kPa above −25 °C), good photothermal conversion effectiveness (kT =0.52), great recyclability (switchable dual modes), and enhanced HIN inhibition (TH = −25 °C and tH = 1322 s). We provide the single and synergistic mechanisms governing the photothermal trapping and ion-induced HIN inhibition. We demonstrate the frozen drop melting, ice block self-moving and large-area snow removing efficacy on BLB as a convenient and long-lasting anti-icing biomass-based covering material via laboratory-scale and outdoor experiments.

CMF/Cu@CuS as photothermal conversion material for solar-driven water evaporation in wet sand systems

Solar-driven water evaporation (WE) is a promising strategy to directly extract freshwater from different water source. Carbonized melamine foam (CMF) was employed as the substrate for loading Cu@CuS with plasma effect and visible-near-infrared light absorption performance as photothermal conversion material (PCM) for WE in the wet sand systems. The porous microstructure, wettability, ultra-light density, and WE property of the obtained CMF/Cu@CuS were characterized and measured. CMF/Cu@CuS has good WE rate and photothermal conversion efficiency (PCE) whether in the wet xalsonte or fine sand system. The WE rate can reach 1.917 kg m−2h−1, with a PCE of 91.75 % in the wet xalsonte system. This work gives a new perspective to expand the application of solar-driven WE technology, especially in the inland and remote areas.

Thiophenol-spaced 2D coordination polymers with extraordinary alkali resistance and efficient photothermal conversion.

Coordination polymers (CPs) based on metal-sulfur bonds are rare; we herein realize a series of thiol-functionalized linker-based CPs (thiol-CPs), MTBT (M = Fe, Co and Zn; TBT = dehydrated 4,4'-thiobisbenzenethiol), which feature an anionic two-dimensional (2D) network, [M(TBT)2]n2n-, with the tetrahedral coordination unit {MS4} serving as a node. These compounds exhibit excellent hydrolytic stability, especially in alkaline solution (20M NaOH for five days), which is the highest value reported for CPs so far. In addition, among them, CoTBT displays favorable photo-thermal conversion effectiveness under an energy power of 0.5 W cm-2 808 nm laser irradiation for 15 s, with the temperature rising rapidly from room temperature to 135.2 °C.

Application of nanotechnology in bladder cancer diagnosis and therapeutic drug delivery.

Bladder cancer (BC) is one of the most common malignant tumors in the urinary system, and its high recurrence rate is a great economic burden to patients. Traditional diagnosis and treatment methods have the disadvantages of insufficient targeting, obvious side effects and low sensitivity, which seriously limit the accurate diagnosis and efficient treatment of BC. Due to their small size, easy surface modification, optical properties such as plasmon resonance, and surface enhanced Raman scattering, good electrical conductivity and photothermal conversion properties, nanomaterials have great potential application value in the realization of specific diagnosis and targeted therapy of BC. At present, the application of nanomaterials in the diagnosis and treatment of BC is attracting great attention and achieving rich research results. Therefore, this paper summarizes the recent research on nanomaterials in the diagnosis and treatment of BC, clarifies the existing advantages and disadvantages, and provides theoretical guidance for promoting the accurate diagnosis and efficient treatment of BC.

Bismuth nanoclusters on nitrogen-doped porous carbon nanoenzyme for cancer therapy.

Among the emerging cancer therapeutic methods, nanocatalytic therapy through the rational design of nanozymes is considered to be a promising strategy. However, high-performance nanozymes with the ability to catalyze the production of toxic substances to efficiently kill cancer cells are still highly desired. Herein, we fabricate bismuth nanoclusters loaded on nitrogen-doped porous carbon (Bi-NC) as a nanozyme for cancer therapy. The Bi-NC nanozyme displays both peroxidase (POD) and glutathione oxidase (GSHOx) biomimetic enzymatic activities, especially in a tumor microenvironment (TME), which catalyzes the production of hydroxyl radicals (·OH) and depletes antioxidant glutathione (GSH), simultaneously. Moreover, Bi-NC exhibits good photothermal conversion performance under near-infrared light irradiation. After surface modification with hyaluronic acid (HA) to improve the dispersity of nanoparticles and their accumulation in tumor tissues, Bi-NC@HA exhibits remarkable antitumor effects through the synergistic effect of catalytic and photothermal therapy. This work provides a new pathway for designing high-performance nanozymes for cancer catalytic therapy.

Supercritical CO2-assisted fabrication of CM-PDA/SF/nHA nanofibrous scaffolds for bone regeneration and chemo-photothermal therapy against osteosarcoma.

Concurrent treatment of tumor recurrence and bone defects after surgical resection of osteosarcoma remains a clinical challenge. Combination therapy based on local drug delivery systems shows great promise in the treatment of osteosarcoma. In this study, curcumin modified polydopamine nanoparticle loaded silk fibroin doped with nano-hydroxyapatite (CM-PDA/SF/nHA) nanofibrous scaffolds were developed to induce bone defect regeneration and chemo-photothermal synergistic effects against osteosarcoma. These scaffolds exhibited good photothermal conversion efficiency and photostability. Moreover, the results of ALP staining and alizarin red S (ARS) staining indicated that the CM-PDA/SF/1%nHA scaffolds had the most obvious promotion effect on early osteogenic differentiation. The results of in vitro and in vivo anti-osteosarcoma activity showed that the CM-PDA/SF/1%nHA scaffolds exhibited higher anti-osteosarcoma activity compared to the control and SF scaffolds. In addition, the CM-PDA/SF/1%nHA scaffolds could promote the proliferation and differentiation of bone marrow mesenchymal stem cells in vitro and new bone production in vivo. Thus, these results suggested that the CM-PDA/SF/1%nHA scaffolds could improve bone defect regeneration and achieve chemo-photothermal synergistic effects against osteosarcoma.

Frontiers in Preparations and Promising Applications of Mesoporous Polydopamine for Cancer Diagnosis and Treatment

Polydopamine (PDA) is a natural melanin derived from marine mussels that has good biocompatibility, biodegradability, and photothermal conversion ability. As a new coating material, it offers a novel way to modify the surface of various substances. The drug loading capacity and encapsulation efficiency of PDA are greatly improved via the use of mesoporous materials. The abundant pore canals on mesoporous polydopamine (MPDA) exhibit a uniquely large surface area, which provides a structural basis for drug delivery. In this review, we systematically summarized the characteristics and manufacturing process of MPDA, introduced its application in the diagnosis and treatment of cancer, and discussed the existing problems in its development and clinical application. This comprehensive review will facilitate further research on MPDA in the fields of medicine including cancer therapy, materials science, and biology.

Iridium Tungstate Nanozyme-Mediated Hypoxic Regulation and Anti-inflammation for Duplex Imaging Guided Photothermal Therapy of Metastatic Breast Tumors.

Metastasis of breast cancer is key to poor prognosis and high mortality. However, the excess reactive oxygen species (ROS) and inflammatory response induced by photothermal therapy (PTT) further aggravate tumor metastasis. Meanwhile, the hypoxic tumor microenvironment promotes tumor cells to metastasize to distant organs. Herein, the intrinsic limitations of PTT for metastatic tumor have been addressed by fabricating polyethylene glycol modified iridium tungstate (IrWOx-PEG) nanoparticles. The as-designed IrWOx-PEG nanoparticles displayed good photothermal (PT) conversion ability for duplex photoacoustic/PT imaging guided PTT and multienzyme mimetic feature for broad-spectrum ROS scavenging. On the one hand, IrWOx-PEG effectively removed excess ROS generated during PTT and reduced inflammation. On the other hand, owing to the catalase-like activity, it preferentially triggered the catalytic production of oxygen by decomposing ROS, leading to relieving of the hypoxic microenvironment. Hence, under bimodal imaging guidance, IrWOx-PEG induced PTT completely eliminated in situ breast cancer in 4T1 tumor-bearing mice with no observable system toxicity, as well as further restricting tumor metastasis to other vital organs (lungs) by ROS scavenging, anti-inflammation, and regulating hypoxic microenvironment. We anticipate that this work will lead to new treatment strategies for other metastatic cancers.

Red light-emitting carbon dots for reduced phototoxicity and photothermal/photodynamic-enhanced synergistic tumor therapy

Photodynamic therapy (PDT) has received extensive attention due to its non-invasive, photo-stimuli-responsive advantages. However, the poor dispersibility of most photosensitizers in water and non-negligible phototoxicity limit their further clinical application. To surmount this dilemma, red-emitting carbon dots (RCDs) with good photothermal conversion ability were synthesized, and photosensitizers Chlorin-e6 (Ce6) were linked onto RCDs to construct the nano-platform RCDs-Ce6 through amide reaction. In this system, RCDs can increase the dispersion of Ce6 to enhance PDT and absorb partitions of daylight to reduce phototoxicity. At the same time, RCDs-Ce6 can achieve simultaneous excitation of photothermal therapy (PTT) and PDT under a single laser, which can overcome the drawbacks of monotherapy while simplifying the treatment procedure. Besides, the excellent fluorescence imaging capability of RCDs-Ce6 could achieve imaging-guided tumor treatment. Spontaneously, both the cytological and 3D multicellular spheroids (3D MCS) levels demonstrated that RCDs-Ce6 had a stronger synergic therapeutic effect with a combination index (CI) of 0.278 and lower phototoxicity. Meanwhile, in vivo experiments showed that RCDs-Ce6 (PTT and PDT) had a more substantial tumor inhibition effect and fluorescence imaging ability with more tumor distribution. This study widened the way for further applications of photodynamic-enhanced therapy with reduced phototoxicity in photosensitizer delivery based on RCDs.