Photothermal Conversion Agents Research Articles

A novel nanodrug for the sensitization of photothermal chemotherapy for breast cancer in vitro.

Owing to the complexity of tumor treatment, clinical tumor treatment has evolved from a single treatment mode to multiple combined treatment modes. Reducing the tolerance of tumors to heat and the toxicity of chemotherapy drugs to the body, as well as increasing the sensitivity of tumors to photothermal therapy and chemotherapy drugs, are key issues that urgently need to be addressed in the current cancer treatment. In this work, polylactic acid-based drug nanoparticles (PLA@DOX/GA/ICG) were synthesized with good photothermal conversion ability by encapsulating the water-soluble anticancer drug doxorubicin (DOX), photothermal conversion agent indocyanine green (ICG) and liposoluble drug gambogic acid (GA) using a double emulsion method. The preparation process of PLA@DOX/GA/ICG was examined. Gambogic acid entrapped in PLA@DOX/GA/ICG nanoparticles could act as an HSP90 protein inhibitor to achieve bidirectional sensitization to chemotherapy and photothermal therapy under 808 nm laser irradiation for the first time, effectively ablating breast cancer cells in vitro. This nanodrug was expected to be used for the efficient treatment of tumors.

Photothermal therapy of xenografted tumor by carbon nanoparticles-Fe(II) complex

Due to the unique structure, carbon nanomaterials could convert near-infrared (NIR) light into heat efficiently in tumor ablation using photothermal therapy (PTT). However, none of them has been applied in clinical treatment, because they have not been approved for clinical evaluations and the precise temperature control facility is scarce. In this study, we designed a temperature-responsive controller for PTT and used carbon nanoparticles-Fe(II) complex (CNSI-Fe) as photothermal conversion agent (PTA) for PTT of tumor in vitro and in vivo. CNSI-Fe was an innovative drug under the evaluations in clinical trials. CNSI-Fe showed excellent photothermal conversion ability in water to increase the water temperature by 40 °C within 5 min under irradiation of 808 nm laser at 0.5 W/cm2. The temperature was precisely controlled at 52 °C for both in vitro and in vivo tumor inhibition. CNSI-Fe with NIR irradiation showed higher tumor cell inhibition than CNSI. In tumor bearing mice, CNSI-Fe with NIR irradiation achieved an inhibition rate of 84.7 % and 71.4 % of them were completely cured. Mechanistically, CNSI-Fe under NIR irradiation induced the radical generation, oxidative damage and ferroptosis to kill tumor. In addition, CNSI-Fe showed good biosafety during PTT according to hematological, serum biological and histopathological examinations. These results indicated that the combination of chemotherapy and PTT provided higher antitumor efficiency using CNSI-Fe as PTA.

Prussian Blue Nanoparticle: From a Photothermal Conversion Agent and a Drug Delivery System, to a Bioactive Drug

Prussian Blue Nanoparticle: From a Photothermal Conversion Agent and a Drug Delivery System, to a Bioactive Drug

Gold nanobipyramids-based laser-activated sealants for effective skin sealing and repair

Anisotropic gold nanostructures have gained increased attention for biomedical applications because of their remarkable optical properties. An emerging type of gold nanostructure—gold nanobipyramids (AuNBP)—has been shown to exhibit superior absorption properties compared to conventionally used gold nanoparticles, which makes them attractive for photothermal applications. We generated a high-shape-purity dispersion of AuNBP using a seed-mediated method and embedded them as photothermal conversion agents in a silk fibroin matrix to investigate their efficacy in photothermal sealing of incisional wounds in immunocompetent mice. These AuNBP-doped laser-activated sealants, or AuNBP-LASE were able to absorb near-infrared laser energy and convert it to heat, thereby inducing transient hyperthermia in the wound and the surrounding tissue. This photothermal conversion facilitated rapid sealing of the skin tissue by the AuNBP-LASE, which resulted in faster functional recovery of skin barrier function compared to nylon sutures at the early stages of repair. Further, the biomechanical properties of the healing skin closed with AuNBP-LASE those of intact skin more rapidly compared to incisions approximated with sutures. Histology studies indicated higher penetration of the LASE within the volume of the incision in skin tissue, lower scab formation, and a similar epidermal gap compared to conventional suturing. These results demonstrate that AuNBP-LASEs can be effective as wound approximation devices for photothermal sealing.

Clinically approved carbon nanoparticles for enhanced photothermal-immunotherapy toward cancer metastasis

The development of new biomedical applications of approved drugs has several advantages in drug translation. In this study, carbon nanoparticle suspension injection (CNSI), clinically approved for lymph node tracer in China, is explored as a photothermal conversion agents for the treatment of metastatic cancer. Metastasis commonly through lymphatic circulation accounts for the principal cause of death in cancer patients. Up to now, immunotherapy has been already used clinically for metastatic cancer. However, the suppressive tumor immune microenvironment limits the effectiveness of immunotherapy. Herein, we use the photothermal effect of CNSI under near-infrared (NIR) irradiation to eliminate primary tumor and induce the immunogenic cell death (ICD). Further, CNSI under irradiation combined with aPD-1 spur immune response and inhibit the growth of distal tumors. Except for the primary tumor, phototherapy was used to treat metastatic lymph nodes synchronously, which can not only eradicate cancer cells, but also directly activate the immune response inside the lymph nodes. Combining with aPD-1 further enhance the anti-tumor effect to block lymphatic metastases and inhibit lung metastases. This study shows that the carbon nanoparticles have potential clinical application prospects for the treatment of tumor metastasis.

Novel small molecule-based organic nanoparticles for second near-infrared photothermal tumor ablation

Second near-infrared (NIR-II,1000 ∼ 1700 nm) therapeutic window presents an increased tissue penetration and elevated maximal permissible exposure in the application of photothermal therapy (PTT). However, the lack of NIR-II photothermal conversion agents (PCAs) limit their further development. In this work, we rationally designed and successfully developed three novel indolium-like heptamethine cyanine dyes (NFs) by installing N,N-diethylamino on the terminal ends of a conjugated polyene backbone and replacing the middle chlorine atom with o-mercapto benzoic acid and p-mercapto benzoic acid. Notably, NF2 with stronger rotating group encapsulated in organic nanoparticles (NF2 NPs) exhibited high photothermal conversion efficiency (PCE), which could come up to (61.3 %). Then we conducted serial experiments to further investigate PTT capability of NF2 NPs 4 T1 cell line and nude mice bearing 4 T1 tumor. As expected, the resulting NF2 NPs presented the excellent photothermal conversion ability and superb PTT effect both in vivo and in vitro. This study will inspire more work for future design and clinical applications of NIR-II therapeutic agents.

Flexible and photo-responsive composite phase change materials for thermal therapy

The medical dressings with appropriate temperature can relieve body pain by promoting blood circulation. In order to endow the thermal compress dressings with multifunction and facilitate their application in different scenarios, the flexible films employing paraffin (PF) as thermal energy storage medium, styrene-ethylene/butylene-styrene (SEBS) triblock copolymer as matrix and graphene as photo-thermal conversion agents were fabricated. The film containing 77 wt% of PF has high latent heat of 157.26 J·g−1 and exhibits smooth and dense morphology. The film also exhibits tensile strain of 2576.75 %, photothermal conversion efficiency of 70.52 % and enviable self-healing properties, which makes it possible to meet the needs of different body parts and reuse in practical applications. In addition, under natural sunlight, the thickness of 3 mm thermal film can maintain the temperature ranging from 40 °C to 50 °C for more than 25 min; under the action of an electrically heated film, the film can maintain at 40 °C to 50 °C for about 22 min. The extraordinarily long thermal therapy time and suitable thermal therapy temperature are remarkable. In summary, the excellent thermal storage properties, mechanical properties, self-healing properties and photothermal conversion properties make it a good application prospect for thermal therapy.

3D-printed NIR-responsive bullets as multifunctional nanodrug platforms for image-guided local chemo-photothermal therapy

Multimodal cancer treatment that combines anticancer drug delivery with other therapeutic strategies, such as photothermal therapy, has shown enormous potential for biomedical applications. However, traditional nanoscale photothermal conversion agents require complicated synthesis processes and lack biosafety, detectability, and mechanical reinforcement ability in the hyperthermia platform. Here, we engineered near-infrared laser (NIR)-responsive bullets as multifunctional nanodrug platforms via a three-dimensional (3D) printing process as an image-guided versatile chemo-photothermal cancer treatment platform. This customizable platform not only serves as a container for anticancer nanodrugs but also possesses excellent radiopacity and high photothermal conversion efficiency, merging on-demand anticancer nanodrug release and hyperthermia effect. Benefiting from the combined chemo-photothermal therapy, the 3D-printed platform showed enhanced cytotoxicity to cancer cells in vitro. Furthermore, in vivo results confirmed effective on-demand nanodrug release and synergistic inhibition of tumor growth upon NIR laser irradiation. 3D-printed NIR-responsive bullets can synergistically enhance anticancer efficiency while evading potential clinical application risks, offering great potential for multimodal cancer therapies.

Propelling Multi-Modal Therapeutics of PEEK Implants through the Power of NO evolving Covalent Organic Frameworks (COFs).

The design and fabrication of NO-evolving core-shell nanoparticles (denoted as NC@Fe), comprised of BNN6-laden COF@Fe3 O4 nanoparticles, are reported. This innovation extends to the modification of 3D printed polyetheretherketone scaffolds with NC@Fe, establishing a pioneering approach to multi-modal bone therapy tailored to address complications such as device-associated infections and osteomyelitis. This work stands out prominently from previous research, particularly those relying on the use of antibiotics, by introducing a bone implant capable of simultaneous NO gas therapy and photothermal therapy (PPT). Under NIR laser irradiation, the Fe3 O4 NP core (photothermal conversion agent) within NC@Fe absorbs photoenergy and initiates electron transfer to the loaded NO donor (BNN6), resulting in controlled NO release. The additional heat generated through photothermal conversion further propels the NC@Fe nanoparticles, amplifying the therapeutic reach. The combined effect of NO release and PPT enhances the efficacy in eradicating bacteria over a more extensive area around the implant, presenting a distinctive solution to conventional challenges. Thorough in vitro and in vivo investigations validate the robust potential of the scaffold in infection control, osteogenesis, and angiogenesis, emphasizing the timeliness of this unique solution in managing complicated bone related infectious diseases.

Copolymerization of Phase Change Materials with Water Resistance Poly(Acrylamide‐Co‐Polyacrylic Acid) Copolymer Encapsulation: Photothermal Conversion and Storage Performance Under Solar Conditions

Currently, the majority of composite phase change materials (PCM) are only available in solid‐phase environments. Therefore, it is important to prepare composite PCM with photothermal conversion capacity, high thermal conductivity, and stability in both solid and aqueous phase conditions. Herein, a composite PCM with high photothermal conversion storage efficiency (92.6%), high energy storage density (147.6 J g−1), and high thermal conductivity (1.19 W m−1 K) is prepared using poly(acrylamide‐co‐polyacrylic acid) copolymer (PAAAM) as the supporting material, boron nitride as the high thermal conductivity filler, and carboxyl‐rich carbon as the photothermal conversion agent and key bridge. With the help of the characteristics of PAAAM, although the PAAAM chain is swollen not broken, it still maintains cross interconnection with PCM in the water‐phase environment, which has excellent encapsulation performance in both the water/solid phase environment. This provides another option for broadening the application of PCM in aqueous solvent conditions.

Near-Infrared Light Triggered the Shape Memory Behavior of Polydopamine-Nanoparticle-Filled Epoxy Acrylate.

Through the effective combination of photothermal conversion agent polydopamine (PDA) nanoparticles and epoxy acrylate polymer (EA), a new kind of near-infrared (NIR) light-triggered shape memory polymer (PDA/EA) is developed. Due to the outstanding photothermal effect of PDA, even with a very low concentration of PDA (0.1 wt.%), when exposed to an 808 nm NIR light with a power of 1 W/cm2, the temporary shapes can be fully light-responsive, recovered in 60 s. Based on dynamic thermomechanical analysis and thermal gravimetric analysis, it can be seen that the introduction of PDA is beneficial for improving dynamic mechanical properties and thermal resistance compared to EA. As an environmentally friendly and highly efficient photoactive SMP, PDA/EA has a great application prospect.

Allomelanin-based biomimetic nanotherapeutics for orthotopic glioblastoma targeted photothermal immunotherapy.

Immune checkpoint blockade (ICB) therapy has shown great potential in the treatment of malignant tumors, but its therapeutic effect on glioblastoma (GBM) is unsatisfactory because of the low immunogenicity and T cell infiltration, as well as the presence of blood-brain barrier (BBB) that blocks most of ICB agents to the GBM tissues. Herein, we developed a biomimetic nanoplatform of AMNP@CLP@CCM for GBM-targeted photothermal therapy (PTT) and ICB synergistic therapy by loading immune checkpoint inhibitor CLP002 into the allomelanin nanoparticles (AMNPs) and followed by coating cancer cell membranes (CCM). The resulting AMNP@CLP@CCM can successfully cross the BBB and deliver CLP002 to GBM tissues due to the homing effect of CCM. As a natural photothermal conversion agent, AMNPs are used for tumor PTT. The increased local temperature by PTT not only enhances BBB penetration but also upregulates the PD-L1 level on GBM cells. Importantly, PTT can effectively stimulate immunogenic cell death to induce tumor-associated antigen exposure and promote T lymphocyte infiltration, which can further amplify the antitumor immune responses of GBM cells to CLP002-mediated ICB therapy, resulting in significant growth inhibition of the orthotopic GBM. Therefore, AMNP@CLP@CCM has great potential for the treatment of orthotopic GBM by PTT and ICB synergistic therapy. STATEMENT OF SIGNIFICANCE: The effect of ICB therapy on GBM is limited by the low immunogenicity and insufficient T-cell infiltration. Here we developed a biomimetic nanoplatform of AMNP@CLP@CCM for GBM-targeted PTT and ICB synergistic therapy. In this nanoplatform, AMNPs are used as both photothermal conversion agents for PTT and nanocarriers for CLP002 delivery. PTT not only enhances BBB penetration but also upregulates the PD-L1 level on GBM cells by increasing local temperature. Additionally, PTT also induces tumor-associated antigen exposure and promotes T lymphocyte infiltration to amplify the antitumor immune responses of GBM cells to CLP002-mediated ICB therapy, resulting in significant growth inhibition of the orthotopic GBM. Thus, this nanoplatform holds great potential for orthotopic GBM treatment.

Selenadiazolesbenzothiadiazole‐Based Small Donor–Acceptor–Donor Dye for Photothermal Therapy in NIR‐II Window

AbstractRecently, photothermal therapy (PTT) has attracted enormous attention because of its low invasiveness, high spatiotemporal selectivity, and good therapeutic effect. Different types of photothermal conversion agents have been developed, particularly the second near‐infrared window (NIR‐II, 1000–1700 nm) organic small molecular dyes which have become an attractive research direction. Herein, a novel and simple donor–acceptor–donor (D–A–D) type NIR‐II dye SeC is designed and synthesized with 2λ4δ2‐[1,2,5]selenadiazolo[3,4‐f]‐2,1,3‐benzothiadiazole structure. To improve capability of SeC for biomedical applications, SeC molecules are encapsulated into DSPE‐PEG2000 to construct nanoparticles SeC‐NPs, which show high photostability and biocompatibility. More importantly, SeC‐NPs exhibited an excellent photothermal performance and display high photothermal conversion efficiency (PCE) of 62% under 808 nm excitation. Because of favorable fluorescence property in NIR‐II window and high PCE, SeC‐NPs are successfully used for NIR‐II imaging and PTT of 4T1 tumor‐bearing mice models. In vivo studies demonstrate SeC‐NPs’ ability to suppress tumor growth under NIR photoirradiation without visible damage to main organs. Overall, this study develops a strategy to design a simple small molecule dye containing selenium for NIR‐II imaging, and SeC‐NPs shows high performance for PTT toward tumor.

A tumor-microenvironment-activated nanoplatform of modified SnFe2O4 nanozyme in scaffold for enhanced PTT/PDT tumor therapy

Phototherapy has attracted widespread attention for cancer treatment due to its noninvasiveness and high selectivity. However, severe hypoxia, overexpressed glutathione and high levels of hydrogen peroxide (H2O2) of tumor microenvironment limit the antitumor efficiency of phototherapy. Herein, inspired by the specific response of nanozymes to the tumor microenvironment, a simple and versatile nanozyme-mediated synergistic dual phototherapy nanoplatform is constructed. In this study, tin ferrite (SnFe2O4, SFO) nanozyme as a photosensitizer was surface modified with polydopamine (denoted as P-SFO) and incorporated into poly(l-lactide) to fabricate an antitumor scaffold fabricated by selective laser sintering. On one hand, SFO nanozyme could act as a photoabsorber to convert light energy into heat for photothermal therapy (PTT). On the other hand, it played a role of photosensitizer in transferring the photon energy to generate reactive oxygen species (ROS) for photodynamic therapy (PDT). Importantly, its multivalent metal ions redox couples would decompose H2O2 into O2 for enhancing O2-dependent PDT and consume glutathione to relieve antioxidant capability of the tumors. Besides, polydopamine as a photothermal conversion agent further enhanced the photothermal performance of SFO. The results revealed the PLLA/P-SFO scaffold possessed a photothermal conversion efficiency of 43.52% for PTT and a high ROS generation capacity of highly toxic ·O2− and ·OH for PDT. Consequently, the scaffold displayed a prominent phototherapeutic effect with antitumor rate of 96.3%. In addition, the PLLA/P-SFO scaffolds possessed good biocompatibility for cell growth. These advantages endow PLLA/P-SFO scaffold with extensive applications in biomedical fields and opened up new avenue towards nanozyme-mediated synergistic phototherapy.

Novel phenothiazine-based amphiphilic Aza-BODIPYs for high-efficient photothermal therapy

Photothermal therapy (PTT) is one of innovative therapeutics types that have been widely applied in cancer treatment, antibiosis and insecticide. It is of significance to investigate photothermal conversion agents (PCAs) with outstanding photothermal conversion ability, photostability and biocompatibility. Here, we developed three novel phenothiazine-based aza-BODIPYs for high-efficient PTT applications. Phenothiazine, as the electron-donating moiety, was introduced into aza-BODIPY core to achieve red-shifted absorption band (∼20–40 nm) with λmax at 730–745 nm and high molar extinction efficient (105 M−1 cm−1). TEG linker was decorated for further increasing the hydrophilicity and biocompatibility of aza-BODIPYs. After self-assembly, the nanoparticles exhibited the preferable photothermal conversion efficient (53–63%) and high photostability with the appropriate hydrated sizes (60–110 nm) and homogenous morphologies. Finally, the aza-BODIPY nanoparticles can significantly decrease the HeLa cell viability under 808 nm laser irradiation, but have the negligible cytotoxicity in dark environments. The series of phenothiazine-based aza-BODIPY PCAs have much potential for the more applications of clinic photothermal therapy in future.

A multifunctional nanoplatform based on Fe3O4@Au NCs with magnetic targeting ability for single NIR light-triggered PTT/PDT synergistic therapy of cancer

Although simultaneous photothermal therapy (PTT) and photodynamic therapy (PDT) have been proven to be beneficial for cancer treatment, high-power laser light sources, shallow penetration depth of light and especially activation by two different light sources make it difficult to be popularized in clinical cancer therapy. Herein, the novel multifunctional Fe3O4@Au nanocomposites (NCs) have been designed and synthesized, which simultaneously act as photothermal conversion agents (PCAs) and photosensitizers (PSs) for PTT/PDT synergistic therapy of human cervical cancer (HeLa) cells using a single excitation light source. Under low-power 808 nm laser irradiation, photothermal conversion efficiency (PCE) of Fe3O4@Au NCs was as high as 39.22% and the cytotoxic singlet oxygen (1O2) could be simultaneously generated. In addition, Fe3O4@Au NCs showed relatively good biocompatibility and low cytotoxicity, which were ideal alternatives for nanotherapeutic agents for treatment of HeLa cells. Meanwhile, PTT only and PTT/PDT dual-modal therapeutic effects of Fe3O4@Au NCs on HeLa cells were compared. The experimental results confirmed that the near-infrared (NIR)-triggered PDT/PTT synergistic therapy of HeLa cells was more efficient due to the synergistic effect. Interestingly, Fe3O4@Au NCs with saturation magnetization (Ms) value of 66.5 emu/g possessed good magnetic responsivity, which could be collected easily with a magnet. The magnetic targeting of Fe3O4@Au NCs could effectively promote their accumulation at tumor sites, thus further enhancing the efficacy of PTT/PDT synergistic therapy of HeLa cells. This study provides a feasible paradigm for magnetic targeting-assisted PTT/PDT synergistic therapy of cancer cells under a single-wavelength excitation and opens up a novel direction for clinical cancer therapy.

Zn-Co metal organic frameworks coated with chitosand and Au nanoparticles for chemo-photothermal-targeted combination therapy of liver cancer.

The toxic effects of chemotherapy drugs on normal tissues are still a major limiting factor in cancer treatment. In this paper, we report a metal-organic framework (Zn-Co ZIF) with chitosan-coated outer layer as a carrier for the drug adriamycin hydrochloride (DOX), a treatment for liver cancer, as a novel anti-cancer nanodrug-enhanced carrier. Gold nanoparticles, a good photothermal conversion agent, were combined with the target SH-RGD during surface functionalisation to prepare Zn-Co ZIF@DOX-CS-Au-RGD (ZD-CAR), a nanoplatform with good photothermal conversion properties and targeting for combined liver cancer therapy. ZD-CAR was developed after RGD accurately targeted the tumour and entered the tumour microenvironment (TME), it cleaves and releases the liver cancer therapeutic agent (DOX) in a weak acidic environment to effectively kill tumour cells. The metal skeleton cleavage releases Co2+, which catalyzes the production of oxygen from H2O2 to alleviate the tumour hypoxic environment. The dissolved oxygen could reach 14 mg/L after adding 80 mg/mL of ZD-CAR. Meanwhile, gold nanoparticles could convert light energy into heat energy under 808 NIR irradiation to induce local superheating and kill tumour cells. In summary, this study developed a nanoplatform that combines chemo-photothermal-targeted therapy. It has shown good therapeutic effeciency in cellular experiments and performance tests and has promising applications in anti-cancer therapy.

Maximum Emission Peak Over 1500nm of Organic Assembly for Blood-Brain Barrier-Crossing NIR-IIb Phototheranostics of Orthotopic Glioblastoma.

The development of blood-brain barrier (BBB)-crossing phototheranostic agents in second near-infrared window (NIR-II), especially in the range of 1500-1700nm (NIR-IIb), affords great opportunities for glioblastoma (GBM) management. Herein, an organic assembly (denoted as LET-12) with the maximum absorption peak at 1400nm and emission peak at 1512nm with trailing over 1700nm through the self-assembly of organic small molecule IR-1064 is designed and subsequently decorated with choline and acetylcholine analogs. The LET-12 can effectively cross BBB through the brain's choline-like receptors-mediated transcytosis and accumulated in tumor tissues, thus achieving fluorescence/photoacoustic (FL/PA) duplex imaging of orthotopic GBM with ≈3.0mm depth and a superior tumor-to-normal tissue signal ratio (20.93 ± 0.59 for FL imaging and 32.63 ± 1.16 for PA imaging, respectively). Owing to its good photothermal conversion ability, the LET-12 also can serve as a photothermal conversion agent, achieving obvious tumor repression of orthotopic murine GBM model after once treatment. The findings indicate that the LET-12 holds great potential for BBB-crossing NIR-IIb phototheranostics of orthotopic GBM. This self-assembly strategy of organic small molecules opens a new avenue for the construction of NIR-IIb phototheranostics.

Triggered release of antimicrobial peptide from microneedle patches for treatment of wound biofilms.

Biofilms pose a great challenge for wound management. Herein, this study describes a near-infrared (NIR) light-responsive microneedle patch for on-demand release of antimicrobial peptide for treatment of wound biofilms. IR780 iodide as a photothermal conversion agent and molecularly engineered peptide W379 as an antimicrobial agent are loaded in dissolvable poly(vinylpyrrolidone) (PVP) microneedle patches followed by coating with a phase change material 1-tetradecanol (TD). After placing in an aqueous solution or biofilm containing wounds ex vivo and in vivo, upon exposure to NIR light, the incorporated IR780 induces light-to-heat conversion, causing the melting of TD. This leads to the dissolution of PVP microneedles, enabling the release of loaded W379 peptide from the microneedles into surrounding regions (e.g., solution, biofilm, wound bed). Compared with traditional microneedle patches, NIR light responsive microneedle patches can program the release of antimicrobial peptide and show high antibacterial efficacy in vitro. Meanwhile, this work indicates that NIR light responsive TD-coated, W379-loaded PVP microneedle patches show excellent antibiofilm activities ex vivo and in vivo. Additionally, this microneedle system could be a promising platform for delivering other antimicrobial agents.

HDAC6 inhibitor loaded bimetallene nanosheets with antagonizing thermoresistance for augmented mild photothermal therapy

Photothermal therapy (PTT) induces thermoresistance through cellular heat shock response, which impairs the therapeutic efficacy of the PTT. To resolve this problem, we developed a photothermal theranostics (denoted as PMH), which integrated the photothermal conversion agent of PdMo bimetallene with histone deacetylase 6 (HDAC6) selected inhibitor (ACY-1215), showing the synergistic antitumor effect both in vitro and in vivo. Mechanistically, under the photoacoustic imaging (PA) navigation, the released ACY-1215 triggered by NIR laser irradiation decrease the heat shock proteins (HSPs) expression and weaken the HDAC6-regulated HSP90 deacetylation, thus hindering the degradation of PTT-induced misfolded or unfold proteins through proteasome dependent pathway. Moreover, mild photothermal therapy (mPTT) treatment compromised the autophagy, which induced by HDAC6 inhibition, leading to mPTT-induced misfolded or unfold proteins further accumulation. Given that inhibition of HDAC6 plus mPTT contribute to tumor eradication. This study develops a promising combination strategy based on mPTT for future cancer treatment.