Effective Photothermal Therapy Research Articles

Neural Progenitor Cell-Mediated Magnetic Nanoparticles for Magnetic Resonance Imaging and Photothermal Therapy of Glioma.

Glioma is the most common primary malignant tumor in the brain. The diagnostic accuracy and treatment efficiency of glioma are facing great challenges due to the presence of the blood-brain barrier (BBB) and the high infiltration of glioma. There is an urgent need to explore the combination of diagnostic and therapeutic approaches to achieve a more accurate diagnosis, as well as guidance before and after surgery. In this work, we induced human induction of pluripotent stem cell into neural progenitor cells (NPCs) and synthesized nanoprobes labeled with enhanced green fluorescent protein (EGFP, abbreviated as MFe3O4-labeled EGFP-NPCs) for photothermal therapy. Nanoprobes carried by NPCs can effectively penetrate the BBB and target glioma for the purpose of magnetic resonance imaging and guiding surgery. More importantly, MFe3O4-labeled EGFP-NPCs can effectively induce local photothermal therapy, conduct preoperative tumor therapy, and inhibit the recurrence of postoperative glioma. This work shows that MFe3O4-labeled EGFP-NPCs is a promising nanoplatform for glioma diagnosis, accurate imaging-guided surgery, and effective photothermal therapy.

Biodegradable MXene Quantum Dots with High Near-Infrared Photothermal Performance for Cancer Treatment.

Photothermal therapy (PTT) offers significant potential in cancer treatment due to its short, simple, and less harmful nature. However, obtaining a photothermal agent (PTA) with good photothermal performance and biocompatibility remains a challenge. MXenes, which are PTAs, have shown promising results in cancer treatment. This study presents the preparation of Ti3C2 MXene quantum dots (MXene QDs) using a simple hydrothermal and ultrasonic method and their use as a PTA for cancer treatment. Compared to conventional MXene QDs synthesized using only the hydrothermal method, the ultrasonic process increased the degree of oxidation on the surface of the MXene QDs. This resulted in the presence of more hydrophilic groups such as hydroxyl groups on the MXene QD surfaces, leading to excellent dispersion in the aqueous system and biocompatibility of the prepared MXene QDs without the need for surface modification. The MXene QDs showed great photothermal performance with a photothermal conversion efficiency of 62.5%, resulting in the highest photothermal conversion efficiency among similar materials reported thus far. Both in vitro and in vivo experiments have proved the potent tumor inhibitory effect of the MXene QD-mediated PTT, with minimal harm to mice. Therefore, these MXene QDs hold a significant promise for clinical applications.

Biofilm microenvironment-activated multimodal therapy nanoplatform for effective anti-bacterial treatment and wound healing

Antimicrobial drug development faces challenges from bacterial resistance, biofilms, and excessive inflammation. Here, we design an intelligent nanoplatform utilizing mesoporous silica nanoparticles doped with copper ions for loading copper sulfide (DM/Cu2+-CuS). The mesoporous silica doped with tetrasulfide bonds responds to the biofilm microenvironment (BME), releasing Cu2+ions, CuS along with hydrogen sulfide (H2S) gas. The release of hydrogen sulfide within 72 h reached 793.5 µM, significantly higher than that observed with conventional small molecule donors. H2S induces macrophages polarization towards the M2 phenotype, reducing inflammation and synergistically accelerating endothelial cell proliferation and migration with Cu2+ions. In addition, H2S disrupts extracellular DNA within biofilms, synergistically photothermal enhanced peroxidase-like activity of CuS to effectively eradicate biofilms. Remarkably, DM-mediated consumption of endogenous glutathione enhances the anti-biofilm activity of H2S and improves oxygen species (ROS) destruction efficiency. The combination of photothermal therapy (PTT), chemodynamic therapy (CDT), and gas treatment achieves sterilization rates of 99.3 % and 99.6 % against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), respectively, in vitro under 808 nm laser irradiation. Additionally, in vivo experiments demonstrate a significant biosafety and antibacterial potential. In summary, the H2S donor developed in this study exhibits enhanced biocompatibility and controlled release properties. By integrating BME-responsive gas therapy with antibacterial ions, PTT and CDT, a synergistic multimodal strategy is proposed to offer new therapeutic approaches for wound healing. Statement of significanceThe advanced DMOS/Cu2+-CuS (DMCC) multimodal therapeutic nanoplatform has been developed for the treatment of drug-resistant bacterial wound infections and has exhibited enhanced therapeutic efficacy through the synergistic effects of photothermal therapy, chemodynamic therapy, Cu2+ions, and H2S. The DMCC exhibited exceptional biocompatibility and could release CuS, Cu2+, and H2S in response to elevated concentrations of glutathione within the biofilm microenvironment. H2S effectively disrupted the biofilm structure. Meanwhile, peroxidase activity of CuS combined with GSH-mediated reduction of Cu2+ to Cu+ generated abundant hydroxyl radicals under acidic conditions, leading to efficient eradication of pathogenic bacteria. Furthermore, both H2S and Cu2+ could modulate M2 macrophages polarization and regulate immune microenvironment dynamics. These strategies collectively provided a novel approach for developing antibacterial nanomedical platforms.

Mild hyperthermia enhanced synergistic uric acid degradation and multiple ROS elimination for an effective acute gout therapy.

Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H2O2) to produce O2, which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine's capacity for UA degradation, O2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout.

Near‐Infrared Light‐Triggered MXene Nanocomposite for Tumor‐Specific Mild Photothermal‐Enhanced Chemodynamic Therapy

AbstractMild photothermal therapy (PTT) is an emerging and elegant approach with minimal adverse effects, demonstrating itself as an effective treatment for cancer. However, potential challenges may arise from the overexpression of heat shock protein 90 (HSP90) and the reliance on monotherapy. Here, a near‐infrared (NIR) light‐triggered MXene nanocomposite (FA@MXene/CuO2/GA) is developed to synergistically combine mild PTT and chemodynamic therapy (CDT) for remarkably effective tumor eradication without any notable tissue damage. Under the irradiation of NIR light, the nanocomposite effectively enhances the mild PTT by suppressing HSP90 expression through the release of gambogic acid (GA) due to the excellent photothermal performance of Ti3C2 MXene nanosheets as well as the tumor‐targeting ability and biocompatibility of the surface‐modified FA‐PEG‐SH. The copper‐based catalyst CuO2 in this system releases Cu2+ in an acid‐triggered manner within the tumor microenvironment, activating the Fenton‐like reaction to generate hydroxyl radicals, and the simultaneous production of H2O2 serves to alleviate the deficiency of endogenous H2O2 within the tumor. Overall, the current work showcases a remarkable synergistic anticancer effect of PTT and CDT, and also proposes new avenues for research in utilizing MXene nanomaterials for tumor treatment.

Therapeutic potentials of FexMoyS-PEG nanoparticles in colorectal cancer: a multimodal approach via ROS-ferroptosis-glycolysis regulation

Improving cancer therapy by targeting the adverse tumor microenvironment (TME) rather than the cancer cells presents a novel and potentially effective strategy. In this study, we introduced FexMoyS nanoparticles (NPs), which act as sequential bioreactors to manipulate the TME. FexMoyS NPs were synthesized using thermal decomposition and modified with polyethylene glycol (PEG). Their morphology, chemical composition, and photothermal properties were characterized. The capability to produce ROS and deplete GSH was evaluated. Effects on CRC cells, including cell viability, apoptosis, and glycolysis, were tested through various in vitro assays. In vivo efficacy was determined using CRC-bearing mouse models and patient-derived xenograft (PDX) models. The impact on the MAPK signaling pathway and tumor metabolism was also examined. The FexMoyS NPs showed efficient catalytic activity, leading to increased ROS production and GSH depletion, inducing ferroptosis, and suppressing glycolysis in CRC cells. In vivo, the NPs significantly inhibited tumor growth, particularly when combined with NIR light therapy, indicating a synergistic effect of photothermal therapy and chemodynamic therapy. Biosafety assessments revealed no significant toxicity in treated mice. RNA sequencing suggested that the NPs impact metabolism and potentially immune processes within CRC cells. FexMoyS NPs present a promising multifaceted approach for CRC treatment, effectively targeting tumor cells while maintaining biosafety. The nanoparticles exhibit potential for clinical translation, offering a new avenue for cancer therapy.

Photothermal performance of CNTs/Ag (NW) nanocomposite in destroying Staphylococcus aureus and Pseudomonas aeruginosa bacteria

In this research, the carbon nanotubes and silver nanowires CNTs/Ag (NW) nanocomposites with different mass ratios were prepared and their photothermal properties in killing Staphylococcus aureus (ATCC 6538) and Pseudomonas aeruginosa (ATCC 9027) bacteria were investigated. Photothermal effect is a characteristic of some materials that absorb visible light at a certain wavelength and convert the absorbed photon into heat and transfer it to the surrounding environment. CNTs/Ag (NW) nanocomposites can have good optical and photothermal properties in the visible and infrared range. Photothermal measurements showed that laser radiation with a wavelength of 808 nm and a power of 1 W/cm2 to CNTs and Ag (NW) with a concentration of 1 g/L in water caused an increase in the water temperature for CNTs by 46 °C and for Ag (NW) by 21.3 °C. Also, for the CNTs/Ag (NW) nanocomposite with a ratio of 10:1, this temperature increase reached 59.2 °C. The effect of photothermal therapy of CNTs, Ag (NW), and CNTs/Ag (NW) composite on two standard bacteria (ATCC 6538) and (ATCC 9027) with laser radiation with a power of 2 W/cm2 for 5 min was performed and found that more than 99 % of bacteria were killed by CNTs/Ag (NW) composite.

Effect of radius-dependent diffusion behavior of various gold nanoparticles on photothermal therapy

Among the various anti-cancer treatments, photothermal therapy (PTT) is gaining traction as it is a non-invasive treatment. PTT is a treatment technique involving the use of a laser to raise the temperature of the target tumor until it dies. In this study, the effects of PTT under various conditions of squamous cell carcinoma (SCC) occurring in the skin were numerically analyzed and optimized. Gold nanoparticles (AuNPs) with different radii were injected into the center of the SCC. Subsequently, the diffusion behavior of the AuNPs was analyzed to calculate the distribution area of the AuNPs that changed over time. Furthermore, at each elapsed time point after injection, the temperature distribution in the tissue was calculated, as treatment was performed using varying laser intensities. The diffusion coefficient of AuNPs was calculated using the Stokes–Einstein equation, and diffusion behavior of AuNPs in biological tissues was analyzed using the convection–diffusion equation. Additionally, temperature distribution was analyzed using the Pennes bioheat equation. The effect of PTT under each condition was quantitatively analyzed using apoptotic variables. As a result, As the radius of AuNPs increased, the optimal treatment start time was derived as 2 h, 8 h, 8 h, and 12 h, respectively, and the laser intensity at that time was derived as 0.44 W, 0.46 W, 0.42 W, and 0.42 W, respectively. The study findings will provide reference for the optimization of the efficacy of PTT.

GSH-Responsive Liposomes with Heat Shock Protein Regulatory Ability for Efficient Photodynamic/Photothermal Combined Therapy of Tumors.

Phototherapy, represented by photodynamic therapy (PDT) and photothermal therapy (PTT), has great potential in tumor treatment. However, the presence of antioxidant glutathione (GSH) and the heat shock proteins (HSPs) expression caused by high temperature can weaken the effects of PDT and PTT. Here, a multifunctional nanocomplex BT&GA@CL is constructed to realize enhanced synergistic PDT/PTT. Cinnamaldehyde liposomes (CLs) formed by cinnamaldehyde dimer self-assembly were loaded with in gambogic acid (GA) and an aggregation-induced emission molecule BT to obtain BT&GA@CL. As a drug carrier, CL can consume glutathione (GSH) and release drugs responsively. The released BT aggregates can simultaneously act as both a photothermal agent and photosensitizer to achieve PDT and PTT under 660 nm laser irradiation. Specifically, GA as an HSP90 inhibitor can attenuate PTT-induced HSP90 protein expression, thereby weakening the tolerance of tumor cells to high temperatures and enhancing PTT. Such a multifunctional nanocomplex simultaneously modulates the content of GSH and HSP90 in tumor cells, thus enhancing both PDT and PTT, ultimately achieving the goal of efficient combined tumor suppression.

Based on polydopamine-coated metal organic framework multifunctional nanoplatform for enhanced photothermal/sonodynamicand treatment combined with checkpoint blockade therapy

To overcome the low efficacy of sonodynamic therapy (SDT) caused by hypoxia in the tumor microenvironment, we developed a multiple anti-tumor nanoplatform with synergistic SDT, photothermal therapy (PTT), and ferroptosis effects. PCN-224@FcCaO2/Mn/dihydroartemisinin/imiquimod/PDA (PFC) was prepared by modified with dihydroartemisinin (DHA), imiquimod (R837), CaO2, ferrocene (Fc) and Mn2+ on the PCN-224 (Cu) to achieve self-replenishment of H2O2/O2 and GSH consumption. FcCaO2 decomposed into H2O2 in the tumor microenvironment, triggering the Fenton effect to produce OH, and Cu2+ reduced the potential loss of OH by the depletion of GSH. Under ultrasonic (US) and laser irradiation, PFC exhibits exciting PTT and SDT effects from polydopamine (PDA) and PCN-224. Mn2+ not only promoted the reaction of H2O2 to produce O2 to effectively enhance SDT but also induced tumor cell apoptosis by Mn2+ combined with DHA. PFC induced ferroptosis via Fe interaction with DHA to produce ROS and reduce the expression of GPX4. The released R837 and tumor-associated antigens from SDT/PTT can produce damage associated molecular patterns (DAMPs), which can initiate adaptive immune responses to kill cancer cells, and released again to promote the tumor immune cycle. What's more, SDT/PTT and ferroptosis combined with aPD-L1 can effectively suppress both primary and distant tumor growth.

A bifunctional biomineralized polyoxometalate enabling efficient Non-Inflammatory NIR-II photothermal tumor therapy

Conventional NIR-I photothermal therapy (PTT) has insufficient penetration depth, and the local tissue damage caused by it often concomitants inflammation. Herein, a bifunctional nanoagent based on bovine serum albumin (BSA) and Mo-polyoxometalate (named as B-POM NPs), was developed via a facile self-assembled method for non-inflammatory near-infrared (NIR)-II PTT of triple-negative breast cancer. Thanks for the BSA modification, the obtained B-POM NPs show excellent biocompatibility with high NIR-II photothermal conversion efficiency of 57.2%. In vivo tumor inhibition efficiency under NIR-II PTT reached up to 87 %. More importantly, it is found that the prepared B-POM NPs also have excellent reactive oxygen species scavenging ability. The inflammatory-related factors, such as TNF-α, IL-6 and IL-1β, are significantly down-regulated, which is much beneficial to reduce side effects of PTT. In brief, this work provides a novel protein-based bifunctional nanoagent to effectively inhibit tumor growth meanwhile alleviate inflammatory post NIR-II PTT, showing good promising in clinical.

Drug repurposing-based nanoplatform via modulating autophagy to enhance chemo-phototherapy against colorectal cancer

Multi-modal combination therapy is regarded as a promising approach to cancer treatment. Combining chemotherapy and phototherapy is an essential multi-modal combination therapy endeavor. Ivermectin (IVM) is a potent antiparasitic agent identified as having potential antitumor properties. However, the fact that it induces protective autophagy while killing tumor cells poses a challenge to its further application. IR780 iodide (IR780) is a near-infrared (NIR) dye with outstanding photothermal therapy (PTT) and photodynamic therapy (PDT) effects. However, the hydrophobicity, instability, and low tumor uptake of IR780 limit its clinical applications. Here, we have structurally modified IR780 with hydroxychloroquine, an autophagy inhibitor, to synthesize a novel compound H780. H780 and IVM can form H780-IVM nanoparticles (H-I NPs) via self-assembly. Using hyaluronic acid (HA) to modify the H-I NPs, a novel nano-delivery system HA/H780-IVM nanoparticles (HA/H-I NPs) was synthesized for chemotherapy-phototherapy of colorectal cancer (CRC). Under NIR laser irradiation, HA/H-I NPs effectively overcame the limitations of IR780 and IVM and exhibited potent cytotoxicity. In vitro and in vivo experiment results showed that HA/H-I NPs exhibited excellent anti-CRC effects. Therefore, our study provides a novel strategy for CRC treatment that could enhance chemo-phototherapy by modulating autophagy.

Rhodium-Rhenium Alloy Nanozymes for Non-inflammatory Photothermal Therapy.

Analogous to thermal ablation techniques in clinical settings, cell necrosis induced during tumor photothermal therapy (PTT) can provoke an inflammatory response that is detrimental to the treatment of tumors. In this study, we employed a straightforward one-step liquid-phase reduction process to synthesize uniform RhRe nanozymes with an average hydrodynamic size of 41.7 nm for non-inflammatory photothermal therapy. The obtained RhRe nanozymes showed efficient near-infrared (NIR) light absorption for effective PTT, coupled with a remarkable capability to scavenge reactive oxygen species (ROS) for anti-inflammatory treatment. After laser irradiation, the 4T1 tumors were effectively ablated without obvious tumor recurrence within 14 days, along with no obvious increase in pro-inflammatory cytokine levels. Notably, these RhRe nanozymes demonstrated high biocompatibility with normal cells and tissues, both in vitro and in vivo, as evidenced by the lack of significant toxicity in female BALB/c mice treated with 10 mg/kg of RhRe nanozymes over a 14 day period. This research highlights RhRe alloy nanoparticles as bioactive nanozymes for non-inflammatory PTT in tumor therapy.

Polyvalent Aptamer-Functionalized NIR-II Quantum Dots for Targeted Theranostics in High PD-L1-Expressing Tumors.

Ag2S quantum dots (QDs) show superior optical properties in the NIR-II region and display significant clinical potential with favorable biocompatibility. However, inherent defects of low targeting and poor solubility necessitate practical modification methods to achieve the theranostics of Ag2S QDs. Herein, we used rolling circle amplification (RCA) techniques to obtain long single-stranded DNA containing the PD-L1 aptamer and C-rich DNA palindromic sequence. The C-rich DNA palindromic sequences can specifically chelate Ag2+ and thus serve as a template to result in biomimetic mineralization and formation of pApt-Ag2S QDs. These QDs enable specific targeting and illuminate hot tumors with high PD-L1 expression effectively, serving as excellent molecular targeted probes. In addition, due to the high NIR-II absorption of Ag2S QDs, pApt-Ag2S QDs exhibit remarkable photothermal properties. And besides, polyvalent PD-L1 aptamers can recognize PD-L1 protein and effectively block the inhibitory signal of PD-L1 on T cells, enabling efficient theranostics through the synergistic effect of photothermal therapy and immune checkpoint blocking therapy. Summary, we enhance the biological stability and antibleaching ability of Ag2S QDs using long single-stranded DNA as a template, thereby establishing a theranostic platform that specifically targets PD-L1 high-expressing inflamed tumors and demonstrates excellent performance both in vitro and in vivo.

Dissolving Hyaluronic Acid-Based Microneedles to Transdermally Deliver Eugenol Combined with Photothermal Therapy for Acne Vulgaris Treatment.

A microneedle transdermal drug delivery system simultaneously avoids systemic toxicity of oral administration and low efficiency of traditional transdermal administration, which is of great significance for acne vulgaris therapy. Herein, eugenol-loaded hyaluronic acid-based dissolving microneedles (E@P-EO-HA MNs) with antibacterial and anti-inflammatory activities are developed for acne vulgaris therapy via eugenol transdermal delivery integrated with photothermal therapy. E@P-EO-HA MNs are pyramid-shaped with a sharp tip and a hollow cavity structure, which possess sufficient mechanical strength to penetrate the stratum corneum of the skin and achieve transdermal delivery, in addition to excellent in vivo biocompatibility. Significantly, E@P-EO-HA MNs show effective photothermal therapy to destroy sebaceous glands and achieve antibacterial activity against deep-seated Propionibacterium acnes (P. acnes) under near-infrared-light irradiation. Moreover, cavity-loaded eugenol is released from rapidly dissolved microneedle bodies to play a sustained antibacterial and anti-inflammatory therapy on the P. acnes infectious wound. E@P-EO-HA MNs based on a synergistic therapeutic strategy combining photothermal therapy and eugenol transdermal administration can significantly alleviate inflammatory response and ultimately facilitate the repair of acne vulgaris. Overall, E@P-EO-HA MNs are expected to be clinically applied as a functional minimally invasive transdermal delivery strategy for superficial skin diseases therapy in skin tissue engineering.

Combination of Efficient Red Fluorescence and High Photothermal Conversion in the Second Near‐Infrared Window from Carbon Dots through Photoinduced Sodium‐Doping Approach

AbstractCarbon dots (CDs) are highly desired in biological applications. However, achieving a balance between photoluminescence (PL) efficiency and photothermal conversion efficiency (PTCE) is challenging. In this study, an unprecedent combination of efficient red fluorescence and high PTCE in the second near‐infrared (NIR‐II) window in a sodium‐doped CDs system is reported. Upon 808 nm laser irradiation, photo‐induced oxidation–reduction reactions happened on the surface of sodium cation‐functionalized CDs (Na‐CDs), leading to the partial reduction of surface‐functionalized sodium (Na) ions. The photo‐reduced Na atoms coordinated with sp2 C domains in the core, resulting in Na‐doped CDs (ir‐Na‐CDs) with an enhanced absorption band in the NIR‐II window and a high PTCE of 43% under 1064 nm laser irradiation (1 W cm−2). Composing the ir‐Na‐CDs with bovine serum albumin (BSA) enhanced the PLQY of the red emission to 31% in water without diminishing the PTCE in the NIR‐II region. Transient absorption spectra revealed that no energy transfer occurred between the red emission center and the NIR‐II absorption band, revealing a novel CDs system with independent Janus photophysical processes. Moreover, ir‐Na‐CDs@BSA exhibited negligible to low cytotoxicity and demonstrated tumor accumulation capacity after intravenous injection, enabling effective tumor photothermal therapy in the NIR‐II region.

Effective photothermal-photodynamic treatment of hepatocellular carcinoma based on polydopamine-coated mesoporous silica nanoparticles

The lack of tumor targeting ability and the ineffectiveness of single treatment modalities are two obstacles in the treatment of hepatocellular carcinoma (HCC). Herein, mesoporous silica nanoparticles (MSNs) with different sizes (MSN100 and MSN50) were synthesized and functionalized with polydopamine (PDA), hypericin B (HB), and arginine-glycine-aspartic acid (RGD) peptides for combined photothermal therapy (PTT) and photodynamic therapy (PDT) of HCC targeting αvβ3 integrin. MSN@PDA-RGD-HB were characterized by various techniques and showed selective drug release, high photothermal conversion efficiency, and reactive oxygen species (ROS) generation under laser irradiation. MSN100@PDA-RGD-HB exhibited higher cellular uptake and HCC toxicity than MSN50@PDA-RGD-HB in vitro, and specifically targeted HCC cells over normal cells. MSN100@PDA-RGD-HB demonstrated high biocompatibility in vivo, as confirmed by the hemolytic test and H&E staining. Importantly, MSN100@PDA-RGD-HB achieved a synergistic effect of PTT and PDT for HCC treatment in mice xenograft tumor model. Therefore, MSN100@PDA-RGD-HB has great potential for tumor therapy in the future.

An innovative stepwise activated coupling reaction for fabricating functional fluorescence probes with potential photosensitive applications

Coupling bright organic emitters with biocomponents such as proteins and amino acids to fabricate biocompatible optical functional materials is receiving increasing attention. Previous reports of an efficient, typical reaction between maleic anhydride (MAH) and amino groups indicated that MAH derivatives have great potential for bioconjugation applications. However, the obstacle of complex synthesis methods and weak fluorescence to this kind of derivative structures based on MAH, have greatly limited their applications. Herein, an innovative strategy was developed based on stepwise activated coupling via a multi-step process. First, a series of donor–acceptor emitting frameworks was constructed by introducing different commercially available electron donors into the electron-withdrawing squaric acid core. Then, these frameworks were further activated to obtain different 3,4-diaryl MAH precursors for bioconjugation, which contributed to a novel light-triggered ring-enlargement effect. Importantly, the MAH precursors triggered catalyst-free coupling reactions at ambient temperature with organic small molecules and biological macromolecules containing primary amine groups. Different fluorescent precursors and abundant biological components were effectively combined, and a water-soluble, biocompatible photosensitizer with efficient photodynamic and photothermal therapy effects was obtained. This strategy is expected to have great potential for biological imaging and theragnostic applications.

DNA-templated synthesis of surface vacancy-rich bifunctional copper sulfide promotes phototherapy via gene regulation

The current photodynamic performance of CuS nanoparticles (CuS NPs) alone is still greatly challenged by the low quantum yield of reactive oxygen species (ROS). At the same time, the efficiency of photothermal therapy (PTT) and photodynamic therapy (PDT) is reduced due to the self-protective ability of tumor cells when attacked by hyperthermia and ROS. To address this issue, we synthesized DCuxS NPs using customized DNA templates through a surface vacancy-rich engineering strategy. In addition to their inherent photothermal properties, the surface vacancy-rich of DCuxS NPs effectively hinders electron-hole pair complexation, thereby enhancing their photodynamic properties. Furthermore, the tumor-targeting NC3S aptamer and the i-motif DNA/Nrf2 siRNA chimera were attached to both ends of the DNA template. The final NDCuxS@siRNA NPs were highly enriched in tumor cells, while the i-motif undergoes a conformational change to release Nrf2 siRNA upon acidic stimulation for Nrf2 pathway blocking to decrease tumor cell protection effect against ROS and high temperature, creating a favorable tumor microenvironment for enhanced PTT and PDT effects. In this study, we explored the potential of DNA templates for engineering nanomaterials, enhanced the photodynamic properties of DCuxS NPs through a surface vacancy-rich strategy, and exploited the versatility of DNA templates to combine phototherapy with gene regulation, providing a promising approach for clinical tumor treatment.

Near-infrared-triggered Dibenzo[a,c][1,2,5]thiadiazolo[3,4-i]phenazine heterocyclic derivatives for type-I photodynamic and photothermal therapy against human nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) remains endemic in southern China. The general therapeutic consensus is to treat the disease with radiotherapy alone or together with concurrent chemotherapy. But the treatment outcome of NPC remains disappointing with bad prognoses, low overall survival rate and severe side effects. Phototherapy can be a promising approach for treating NPC due to its excellent spatiotemporal selectivity, negligible drug resistance and minimal invasiveness. In this work, two photosensitizers (DTP-Ph and DTP-Et) with similar donor-acceptor structure were designed and constructed for the treatment of NPC. Remarkably, DTP-Ph and DTP-Et show different photo-physicochemical properties as well as mechanisms of phototherapeutic actions, especially DTP-Ph, which exhibits synergistic type-I photodynamic therapy (PDT) and photothermal therapy (PTT) effect under near-infrared (NIR) activation. DTP-Et and DTP-Ph were further encapsulated with F127 to obtain nanoparticles with good water solubility. In intro and in vivo phototherapy evaluations of DTP-Ph NPs display promising phototherapeutic activity with low IC50 value and good tumor growth inhibition (TGI) against human nasopharyngeal carcinoma cell line CNE2 and tumor-bearing xenograft model.