Effective Photothermal Therapy Research Articles

A pH-response chemotherapy synergistic photothermal therapy for tumor suppression and bone regeneration by mussel-inspired Mg implant.

Primary malignant bone tumors can be life-threatening. Surgical resection of tumor plus chemotherapy is the standard clinical treatment. However, postoperative recovery is hindered due to tumor recurrence caused by residual tumor cells and bone defect caused by resection of tumor tissue. Herein, a multifunctional mussel-inspired film was fabricated on Mg alloy, that is, an inner hydrothermal-treated layer, a middle layer of polydopamine, and an outer layer of doxorubicin. The modified Mg alloy showed excellent photothermal effect and thermal/pH-controlled release of doxorubicin. The synergistic effect of chemotherapy and photothermal therapy enabled the modified Mg alloy to kill bone tumor in vitro and inhibit tumor growth in nude mice. Moreover, because of the controlled release of Mg ions and biocompatibility of polydopamine, the modified Mg alloy supported extracellular matrix mineralization, alkaline phosphatase activity, and bone-related gene expression in C3H10T1/2. Bone implantation model in rats verified that the modified Mg showed excellent osteointegration. These findings prove that the use of mussel-inspired multifunction film on Mg alloy offers a promising strategy for the therapy of primary malignant bone tumor.

NIR II Luminescence Imaging for Sentinel Lymph Node and Enhanced Chemo-/Photothermal Therapy for Breast Cancer.

In this research, a NIR II luminescence imaging and enhanced chemo-/photothermal therapy system of CuS-DOX-Nd/FA NPs for breast cancer and lymph node tracing under single 808 nm irradiation is proposed. Nd-DTPA molecular cluster with the NIR II imaging effect as the carrier was designed to load the ultrasmall CuS nanoparticles and chemotherapeutic drug doxorubicin hydrochloride (DOX). The composite probe is used for tumor lesion imaging and tracking the breast cancer sentinel lymph nodes with simultaneous chemo-/photothermal therapy (PTT) for breast cancer under the single 808 nm laser. This designed probe not only has high permeability and retention (EPR) targeting effect but also can respond to the tumor microenvironment (TME), realizing more precise and efficient release of DOX at the cancer focus. At the same time, CuS as a drug carrier has a good photothermal therapy effect (photothermal conversion efficiency: 27.9%). The serialized released chemotherapy DOX and synergistic PTT effect can be used to the treat the in situ breast cancer land and simultaneously kill the metastasis cancer. The system made the combined molecular clusters Nd-DTPA achieve NIR II imaging of tumor lesions of breast cancer and lymph node to obtain the integration of diagnosis of the transferred disease for better prognosis. The feasibility of the system had obvious tumor growth inhibition effect with NIR II imaging guided is verified by a series of in vitro and in vivo experiments.

Self‐Assembled Metal–Organic Framework Stabilized Organic Cocrystals for Biological Phototherapy

AbstractOrganic self‐assembled co‐crystals have garnered considerable attention due to their facile synthesis and intriguing properties, but supramolecular interactions restrict their stability in aqueous solution, which is especially important for biological applications. Herein, we report on the first biological application of aqueous dispersible self‐assembled organic co‐crystals via the construction of metal–organic framework (MOF) ‐stabilized co‐crystals. In particular, we built an electron‐deficient MOF with naphthalene diimide (NDI) as the ligand and biocompatible Ca2+ as the metal nodes. An electron donor molecule, pyrene, was encapsulated to form the host–guest MOF self‐assembled co‐crystal. We observed that such MOF structure leads to uniquely high‐density ordered arrangement and the close intermolecular distance (3.47 Å) of the charge transfer pairs. Hence, the concomitant superior charge transfer interaction between pyrene/NDI can be attained and the resultant photothermal conversion efficiency of Py@Ca‐NDI in aqueous solution can thus reach up to 41.8 %, which, to the best of our knowledge, is the highest value among the reported organic co‐crystal materials; it is also much higher than that of the FDA approved photothermal agent ICG as well as most of the reported MOFs. Based on this realization, as a proof of concept, we demonstrated that such a self‐assembled organic co‐crystal platform can be used in biological applications that are exemplified via highly effective long wavelength light photothermal therapy.

Self-Assembled Metal-Organic Framework Stabilized Organic Cocrystals for Biological Phototherapy.

Organic self-assembled co-crystals have garnered considerable attention due to their facile synthesis and intriguing properties, but supramolecular interactions restrict their stability in aqueous solution, which is especially important for biological applications. Herein, we report on the first biological application of aqueous dispersible self-assembled organic co-crystals via the construction of metal-organic framework (MOF) -stabilized co-crystals. In particular, we built an electron-deficient MOF with naphthalene diimide (NDI) as the ligand and biocompatible Ca2+ as the metal nodes. An electron donor molecule, pyrene, was encapsulated to form the host-guest MOF self-assembled co-crystal. We observed that such MOF structure leads to uniquely high-density ordered arrangement and the close intermolecular distance (3.47 Å) of the charge transfer pairs. Hence, the concomitant superior charge transfer interaction between pyrene/NDI can be attained and the resultant photothermal conversion efficiency of Py@Ca-NDI in aqueous solution can thus reach up to 41.8 %, which, to the best of our knowledge, is the highest value among the reported organic co-crystal materials; it is also much higher than that of the FDA approved photothermal agent ICG as well as most of the reported MOFs. Based on this realization, as a proof of concept, we demonstrated that such a self-assembled organic co-crystal platform can be used in biological applications that are exemplified via highly effective long wavelength light photothermal therapy.

Photodynamic and photothermal co-driven CO-enhanced multi-mode synergistic antibacterial nanoplatform to effectively fight against biofilm infections

Photothermal therapy (PTT) and photodynamic therapy (PDT) have garnered much attention for effectively treating biofilm infections. However, even highly efficient PTT reagents and photosensitizers still require high concentration and irradiation doses to ablate biofilms due to their limited permeability in biofilms, while these attempts tend to cause severe tissue damage and inflammation. Herein, a CO-enhanced multi-mode synergistic antibacterial nanoplatform (ICG&CO@G3KBPY) with controllable CO generation behavior, notably enhanced biofilm penetration, antibacterial, biofilm ablation, and anti-inflammatory activity was effectively developed to combat biofilm infections. ICG&CO@G3KBPY is constructed by physically encapsulating indocyanine green (ICG) and manganese pentacarbonyl bromide (MnBr(CO)5) into a 2,2′-bipyridine-4-carboxylic (BPY)-modified peptide dendrimer-based nanogel (G3KBPY). ICG&CO@G3KBPY can rapidly generate massive quantities of CO under the co-driven effects of PTT and PDT. Notably, the generated CO not only promotes the biofilm penetration of ICG and enhances the antibacterial and biofilm eradication performance of PTT and PDT, but also significantly alleviates the inflammatory response caused by bacterial infection, PTT and PDT. The combination of CO, PTT, and PDT offers excellent biofilm ablation effects in treating urinary catheter infection and subcutaneous abscesses, accompanied by good biocompatibility. This study provides an efficient and safe multi-mode synergistic antibacterial strategy for combatting biofilm infections.

Rational Design of Near‐Infrared Aza‐Platinum‐Dipyrromethene‐Based Nanophototherapy Agent with Multistage Enhancement for Synergistic Antitumor Therapeutics

The development of innovative synergistic phototherapy (SPT) agent with excellent photodynamic therapy (PDT) and photothermal therapy (PTT) effects for efficient antitumor is of great significance. However, the low photothermal conversion efficiency or low singlet oxygen yield of SPT agent during the phototherapy process will result in inefficient tumor therapy. Herein, a new near‐infrared (NIR) SPT agent based on aza‐platinum‐dipyrromethene dye (D‐3) with synergistic PDT and PTT effects is rationally designed and synthesized by the metallization and halogenation of aza‐dipyrromethene simultaneously. The introduction of iodine atoms and Pt(II) ion to aza‐dipyrromethene skeleton can not only effectively promote the excited electrons to undergo intersystem crossing process for improving singlet oxygen (1O2) generation capability, but also inhibit radiative transition process for boosting photothermal conversion properties. For biological exploration, the biocompatible D‐3 nanomaterials (APIDNs) with excellent concentration‐dependent photoacoustic and photothermal properties are prepared, thus visibly guiding synergetic PDT and PTT effects for inhibiting the growth of tumor cells in vivo. This work demonstrates the superior therapy effects of APIDNs and its negligible dark cytotoxicity. The novel strategy reported in this work will offer a new way to design new‐generation NIR aza‐metal‐dipyrromethene‐based dyes for developing superior SPT agents.

Indocyanine green-carrying polymeric nanoparticles with acid-triggered detachable PEG coating and drug release for boosting cancer photothermal therapy

In order to boost anticancer efficacy of indocyanine green (ICG)-mediated photothermal therapy (PTT) by promoting intracellular ICG delivery, the ICG-carrying hybrid polymeric nanoparticles were fabricated in this study by co-assembly of hydrophobic poly(lactic-co-glycolic acid) (PLGA) segments, ICG molecules, amphiphilic tocopheryl polyethylene glycol succinate (TPGS) and pH-responsive methoxy poly(ethylene glycol)-benzoic imine-1-octadecanamine (mPEG-b-C18) segments in aqueous solution. The ICG-loaded nanoparticles were characterized to have ICG-containing PLGA core stabilized by hydrophilic PEG-rich surface coating and a well-dispersed spherical shape. Moreover, the ICG-loaded nanoparticles in pH 7.4 aqueous solution sufficiently inhibited ICG self-aggregation and leakage, thereby increasing aqueous photostability of ICG molecules. Notably, when the solution pH was reduced from pH 7.4–5.5, the acid-triggered hydrolysis of benzoic-imine linkers within mPEG-b-C18 remarkably facilitated the detachment of mPEG segments from ICG-loaded nanoparticles, thus accelerating ICG release. The findings of in vitro cellular uptake and cytotoxicity studies further demonstrated that the PEGylated ICG-carrying hybrid nanoparticles were efficiently internalized by MCF-7 cells compared to free ICG and realized intracellular acid-triggered rapid ICG liberation, thus enhancing anticancer effect of ICG-mediated PTT to potently kill cancer cells.

Photothermal therapy based on magnetic nanoparticles in cancer

Photothermal therapy (PTT) is an extensively used kind of cancer treatment based on thermal energy, which has been technically mature relative to other emerging nanotechnologies. Initially, single-phase magnetic nanoparticles (NPs) have been used for PTT due to their excellent biocompatibility and photothermal properties. With the boom of research, various types of composite-phase NPs have been developed to improve the efficiency and broaden the application range of PTT. The synergistic effect of PTT and other therapies have also gradually attracted the attention of researchers in achieving enhanced tumor elimination. However, the intrinsic obstacles of PTT have restricted the widespread clinical application, and the vague pathological mechanisms of PTT have also made it more difficult to promote clinical translation. In this Perspective, the current research progress of PTT including a diversified selection of magnetic NPs prospects toward the clinic, and the potential pathological mechanism will be overviewed. Meanwhile, the potential outlook of open challenges will be discussed for the utility of PTT.

Cancer Cytomembrane-Cloaked Prussian Blue Nanoparticles Enhance the Efficacy of Mild-Temperature Photothermal Therapy by Disrupting Mitochondrial Functions of Cancer Cells.

Despite its success against cancer, photothermal therapy (PTT) (>50 °C) suffers from several limitations such as triggering inflammation and facilitating immune escape and metastasis and also damage to the surrounding normal cells. Mild-temperature PTT has been proposed to override these shortcomings. We developed a nanosystem using HepG2 cancer cell membrane-cloaked zinc glutamate-modified Prussian blue nanoparticles with triphenylphosphine-conjugated lonidamine (HmPGTL NPs). This innovative approach achieved an efficient mild-temperature PTT effect by downregulating the production of intracellular ATP. This disrupts a section of heat shock proteins that cushion cancer cells against heat. The physicochemical properties, anti-tumor efficacy, and mechanisms of HmPGTL NPs both in vitro and in vivo were investigated. Moreover, the nanoparticles cloaked with the HepG2 cell membrane substantially prolonged the circulation time in vivo. Overall, the designed nanocomposites enhance the efficacy of mild-temperature PTT by disrupting the production of ATP in cancer cells. Thus, we anticipate that the mild-temperature PTT nanosystem will certainly present its enormous potential in various biomedical applications.

Exfoliation and in situ functionalization of MoS2 nanosheets for MRI-guided combined low-temperature photothermal therapy and chemotherapy

Traditional photothermal therapy (PTT) usually requires hyperthermia (greater than50 °C) to mediate effective tumor ablation, which could inevitably induce heating damage to the adjacent normal tissues. Therefore, to achieve effective tumor killing at relatively low temperature is crucial to improve the application of PTT. MoS2, as an attractive photothermal agents, have attracted much attention in biomedical applications. But the separation of exfoliation and functionalization of MoS2 nanosheets (NSs) partly complicates the preparation process of MoS2 NSs-based theranostic nanomaterials. Herein, we formulated a facile one-pot approach for the exfoliation and in situ functionalization of single-layer MoS2 nanosheets by using bovine serum albumin template gadolinium oxide (BSA-Gd2O3) nanoparticles as the exfoliating agent and magnetic resonance imaging (MRI) T1 contrast agent. On this basis, hyaluronic acid (HA) was further conjugated to target cancer cells with overexpression of CD44, and then gambogic acid (GA), a natural heat shock protein 90 inhibitor and antitumor drug was loaded, which could reduce the thermo-resistance of tumor cells and achieve effective PTT at a mild temperature (43–45 °C). In this research, both in vitro and in vivo experiments have confirmed that the GA/MoS2/BSA-Gd2O3-HA nanocomposite possesses good biocompatibility and is promising for the application in MRI-guided combined low-temperature PTT and chemotherapy.

Construction of multifunctional hydrogel based on the tannic acid-metal coating decorated MoS2 dual nanozyme for bacteria-infected wound healing

Bacterial infection, tissue hypoxia and inflammatory response can hinder the infected wound repair process. To mitigate the above issues, tannic acid-chelated Fe-decorated molybdenum disulfide nanosheets (MoS2@TA/Fe NSs) with dual enzyme activities were developed and anchored to a multifunctional hydrogel. The hydrogel exhibited excellent antibacterial ability owing to the combined effects of photothermal therapy (PTT), glutathione (GSH) loss, and the peroxidase (POD)-like activity (catalyse H2O2 into ·OH under acid condition) of MoS2@TA/Fe NSs. Benefitting from the catalase (CAT)-like activity, the hydrogel could decompose H2O2 into O2 at neutral pH to relieve hypoxia and supply adequate O2. POD-like activity was mainly attributed to MoS2 NSs, while CAT-like activity was primarily due to TA/Fe complex. Moreover, MoS2@TA/Fe NSs endowed the hydrogel with outstanding anti-oxidant ability to scavenge redundant reactive oxygen species (ROS) and reactive nitrogen species (RNS) under neutral environment to maintain the balance of antioxidant systems and prevent inflammation. In addition, the hydrogel could inhibit the release of inflammatory factors for the anti-inflammatory property of TA. TA retained partial phenolic hydroxyl groups, which cross-linked the nanosheets to the network structure of the hydrogel and promoted the adhesion of hydrogels. Due to the dynamic boron ester bonds between polyvinyl alcohol (PVA), dextran (Dex), MoS2@TA/Fe, and borax, the hydrogel demonstrated fast self-healing and rapid shape adaptability. This shape-adaptable adhesive hydrogel could fill the whole wound and closely contact the wound, ensuring that it achieved its functions with maximum efficiency. The MoS2@TA/Fe nanozyme-anchored multifunctional hydrogel showed high potential for bacteria-infected wound healing.

Anisotropic Truncated Octahedral Au with Pt Deposition on Arris for Localized Surface Plasmon Resonance-Enhanced Photothermal and Photodynamic Therapy of Osteosarcoma.

The multifunctional combined nanoplatform has a wide application prospect in the synergistic treatment of cancer. Nevertheless, the traditional treatment of phototherapy is limited by the catalytic nanomaterial itself, so the effect is not satisfactory. Here, the arris of the anisotropic truncated octahedral Au (TOh Au) was coated with noble metal Pt to form a spatial separation structure, which enhanced the local surface plasmonic resonance and thus boosted the photocatalytic effect. In this system, the highly efficient photocatalysis provides a strong guarantee for oncotherapy. On the one hand, the structure of arris deposition adequately improves the efficiency of photothermal conversion, which substantially improves the effectiveness of photothermal therapy. On the other hand, in situ oxygen production of Pt ameliorates tumor hypoxia, and through the O2 self-production and sales mode, the growth and development of tumor were inhibited. Meanwhile, under the enhanced photocatalysis, more O2 were produced, which greatly evolved the treatment effect of photodynamic therapy. In the end, the addition of hyaluronic acid can specifically target osteosarcoma cells while improving the retention time and biocompatibility of the material in the body. Thus, the nanocomposite shows superexcellent synergistic enhancement of photothermal conversion efficiency and photodynamic capability in vitro and in vivo, which provides a potential possibility for osteosarcoma cure.

Metal organic framework-coated gold nanorod as an on-demand drug delivery platform for chemo-photothermal cancer therapy

Chemo-photothermal therapy based on nanoparticles has emerged as a promising strategy for cancer treatment. However, its therapeutic efficacy and application potential are largely subjected to the uncontrollability and biotoxicity of functional nanoplatforms. Herein, a novel biocompatible and biodegradable metal organic framework (MOF), which was constructed by growing crystalline zeolitic imidazolate framework-8 on gold nanoroad (Au@ZIF-8), was designed and fabricated for efficient drug loading and controlled release. Owing to the large surface area and guest-matching pore size of ZIF-8, doxorubicin (DOX) was successfully loaded into the Au@ZIF-8 with a high drug loading efficiency of ~ 37%. Under NIR light or weakly acidic environment, the ZIF-8 layer was quickly degraded, which resulted in an on-demand drug release in tumour site. More importantly, under the irradiation of near infrared (NIR) laser, highly efficient cancer treatment was achieved in both in vitro cell experiment and in vivo tumour-bearing nude mice experiment due to the synergistic effect of photothermal (PTT) therapy and chemotherapy. In addition, the in vivo study revealed the good biocompatibility of Au@ZIF-8. This work robustly suggested that Au@ZIF-8 could be further explored as a drug delivery system for chemo-photothermal synergistic therapy.

Ganoderma Lucidum Polysaccharides Enhance the Abscopal Effect of Photothermal Therapy in Hepatoma-Bearing Mice Through Immunomodulatory, Anti-Proliferative, Pro-Apoptotic and Anti-Angiogenic.

Hepatocellular carcinoma is a malignant tumor with high morbidity and mortality, a highly effective treatment with low side effects and tolerance is needed. Photothermal immunotherapy is a promising treatment combining photothermal therapy (PTT) and immunotherapy. PTT induces the release of tumor-associated antigens by ablating tumor and Ganoderma lucidum polysaccharides (GLP) enhance the antitumor immunity. Results showed that Indocyanine Green (ICG) was successfully encapsulated into SF-Gel. ICG could convert light to heat and SF-Gel accelerates the photothermal effect in vitro and in vivo. PTT based on ICG/ICG-SF-Gel inhibited the growth of primary and distal tumors, GLP enhanced the inhibitory efficacy. ICG/ICG-SF-Gel-based PTT and GLP immunotherapy improved the survival time. ICG/ICG-SF-Gel-based PTT induces tumor necrosis and GLP enhanced the photothermal efficacy. ICG/ICG-SF-Gel-based PTT inhibited cell proliferation and angiogenesis, induced cell apoptosis, enhanced cellular immunity, and GLP enhanced these effects. In conclusion, GLP could enhance the abscopal effect of PTT in Hepatoma-bearing mice.

The synergistic effect of enhanced photocatalytic activity and photothermal effect of oxygen-deficient Ni/reduced graphene oxide nanocomposite for rapid disinfection under near-infrared irradiation

The rational design of high antibacterial efficiency are urgently needed as the occurrence of drug-resistance issues. Hence, Ni/reduced graphene oxide nanocomposite (Ni/rGO) with different amounts of oxygen vacancies were fabricated for efficient disinfection. The optimized Ni/rGO (A100) exhibited highly effective inactivation efficacy of 99.6% and 99.5% against Escherichia coli and Bacillus subtilis within 8 min near-infrared (NIR) irradiation through the synergistic effects of photothermal therapy and oxidative damage, which were much higher than single treatment. The A100 nanocomposite achieved an extraordinary photothermal conversion efficiency (35.78%) under the 808 nm irradiation for enhanced photothermal hyperthermia, thereby destroying the cell membrane and accelerating the GSH depletion. The radical scavenger experiment confirmed that •O2- and •OH play the chief role in photodisinfection reaction. Besides, A100 could exert significant damage on the ATP synthesis. The excellent photothermal performance and photocatalytic activity can be attributed to the appropriate oxygen vacancy density, which improves the absorption of NIR light and facilitates the separation of photogenerated electron-hole pairs. Besides, the higher NiO content of A100 contributed to improving the photocatalytic effect. Our work demonstrated a promising strategy for efficient water pollution purification caused by pathogenic bacteria.

Unadulterated Organic Nanoparticles with Small Sizes for Robust Tumor Imaging and Photothermal Treatment

AbstractPhototheranostics integrating optical imaging and phototherapy have attracted massive attention in the context of precise tumor therapy. However, most of the reported phototheranostic systems have large sizes and complex structures due to either the extraneous carriers or cargos. Herein, the organic nanoparticles (terrylenediimide (TDI) NPs) are obtained from a TDI‐based single component in the absence of additives. The as‐prepared TDI NPs possess favorable small sizes of less than 20 nm, good photothermal stability, and high photothermal conversion efficiency. Especially, TDI NPs have the capacity for rapid and lasting tumor imaging, and effective photothermal therapy of cervical cancer upon irradiation. This work provides an alternative method to prepare multifunctional nanomaterials with simple structures, and sheds light on the potential applications of dye molecules as intrinsic theranostic agents.

Mn2+-doped Prussian blue nanoparticles for T1-T2 dual-mode magnetic resonance imaging and photothermal therapy in vitro

To prepare Mn2+-doped Prussian blue nanoparticles (Mn-PB NPs) for T1-T2 dual-mode magnetic resonance imaging (MRI) and photothermal therapy in vitro. Mn-PB NPs were prepared based on manganese chloride, ferrous chloride and potassium ferricyanide using the microemulsion method. The performance of T1-T2 dual-mode MRI with Mn-PB NPs and the photothermal property of the nanoparticles were assessed. CCK-8 assay and AM/PI double staining were used to evaluate the effect of photothermal therapy in vitro using the parepared nanoparticles. The prepared Mn-PB NPs had a mean particle size of 39.46±0.42 nm with a Zeta potential of -25.9±1.2 mV and exhibited a good dispersibility and uniform particle size. In MRI using the nanoparticles, the r1 and r2 values reached 0.68 and 3.65 (mmol/L)-1s-1, respectively, indicating good performance of Mn-PB NPs for T1 and T2 enhancement in MRI. When irradiated with 808 nm laser for 10 min, Mn-PB NPs showed a temperature rise to 90 ℃ to cause significant reduction of cell survival. CCK-8 assay and AM/PI double staining confirmed that Mn-PB NPs were capable of efficient killing of HepG2 cells upon 808 nm laser irradiation. The Mn-PB NPs prepared in this work have uniform particle size and show good performances both in MRI for T1 and T2 enhancement and in photothermal therapy in vitro without obvious cytotoxicity.

Effective Photothermal Therapy Mediated by Indocyanine Green Nanoparticle Tip-Loaded Microneedles to Enhance Checkpoint Inhibitor Immunotherapy for Melanoma Treatment

Effective Photothermal Therapy Mediated by Indocyanine Green Nanoparticle Tip-Loaded Microneedles to Enhance Checkpoint Inhibitor Immunotherapy for Melanoma Treatment

Targeting the tumor microenvironment with amphiphilic near-infrared cyanine nanoparticles for potentiated photothermal immunotherapy

Despite the potential of photothermal therapy (PTT) for cancer treatments, PTT alone has limitations in treating metastatic tumors and preventing tumor recurrence, highlighting the need to combine PTT with immunotherapy. This study reports tumor microenvironment (TME)-targeting, near-infrared (NIR) dye derivative—based nanomedicine for effective combined PTT—immunotherapy. Amphiphilic NIR dye cyanine derivatives are used not only for constructing the nanoparticle mass, but also for creating a stable complex with CpG adjuvant; a peptide specific to fibronectin extra domain B (APTEDB) is also introduced as a TME-targeting ligand, yielding the TME-targeting nanomedicine, APTEDB-cyNP@CpG. APTEDB-cyNP@CpG shows cancer-targeting ability in EDB-overexpressing CT26 colon tumor-bearing mice. When combined with laser irradiation, it induces immunogenic cell death (ICD) and subsequently leads to significant increase in CD8+ T cell population in the tumor, resulting in greater antitumor therapeutic efficacy than does cyNP@CpG lacking the TME-targeting ligand. Moreover, the combination of APTEDB-cyNP@CpG–based PTT and an immune checkpoint blockade (ICB) antibody leads to remarkable antitumor efficacy against the laser-irradiated primary tumor as well as distant tumor through potentiation of systemic cancer cell-specific T cell immunity. Furthermore, the PTT-immunotherapy combination regimen is highly effective in inhibiting tumor recurrence and metastasis.

Reduction and temperature dually-triggered size-shrinkage and drug release of micelles for synergistic photothermal-chemotherapy of cancer

Reduction and temperature dually responsive poly(2-(2-methoxyethoxy)ethylmethacrylate-co-oligo(ethylene glycol) methacrylate)-b-poly(ε-caprolactone)-SS-poly(ε-caprolactone)-b-poly(2-(2-methoxyethoxy)ethylmethacrylat-co-oligo(ethylene glycol) methacrylate) (P(MEO2MA-co-OEGMA)-b-PCL-SS-PCL-b-P(MEO2MA-co-OEGMA)) was synthesized by the combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP). The copolymer can self-assemble into spherical micelles. After loading doxorubicin (DOX) and photothermal agent Indocyanine green (ICG), the micelles were endowed with synergistic effect of chemotherapy and photothermal therapy to cancer through reduction and temperature dually triggered size-shrinkage and drug release. The micelles showed good reduction and temperature responsiveness due to the presence of disulfide bond and thermoresponsive segments in copolymer. Under reducing conditions, the disulfide bond broke and the micelles were converted into micelles with half the original size, which was conducive to drug release. Near Infrared light (NIR) promoted the photothermal conversion of ICG, so that the micelle underwent a temperature response transition and further promoted the release of drugs. The micelles showed drug release rate, high photothermal conversion efficiency, highly cytotoxic to cancer cells and excellent synergistic photothermal-chemotherapy effect.