Long‐Range Nanoparticle Surface‐Energy‐Transfer Ruler for Monitoring Photothermal Therapy Response

A recent gold nanotechnology‐driven approach opens up a new possibility for the destruction of cancer cells through photothermal therapy. Ultimately, photothermal therapy may enter into clinical therapy and, as a result, there is an urgent need for techniques to monitor the tumor response to therapy. Driven by this need, a nanoparticle surface‐energy‐transfer (NSET) approach to monitor the photothermal therapy process by measuring a simple fluorescence intensity change is reported. The fluorescence intensity change is due to the light‐controlled photothermal release of single‐stranded DNA/RNA via dehybridization during the therapy process. Time‐dependent results show that just by measuring the fluorescence intensity change, the photothermal therapy response during the therapy process can be monitored. The possible mechanism and operating principle of the NSET assay are discussed. Ultimately, this NSET assay could have enormous potential applications in rapid, on‐site monitoring of the photothermal therapy process, which is critical to providing effective treatment of cancer and multidrug‐resistant bacterial infections.     

Dual‐Peak Absorbing Semiconducting Copolymer Nanoparticles for First and Second Near‐Infrared Window Photothermal Therapy: A Comparative Study

Near‐infrared (NIR) light is widely used for noninvasive optical diagnosis and phototherapy. However, current research focuses on the first NIR window (NIR‐I, 650–950 nm), while the second NIR window (NIR‐II, 1000–1700 nm) is far less exploited. The development of the first organic photothermal nanoagent (SPN_I‐II) with dual‐peak absorption in both NIR windows and its utilization in photothermal therapy (PTT) are reported herein. Such a nanoagent comprises a semiconducting copolymer with two distinct segments that respectively and identically absorb NIR light at 808 and 1064 nm. With the photothermal conversion efficiency of 43.4% at 1064 nm generally higher than other inorganic nanomaterials, SPN_I‐II enables superior deep‐tissue heating at 1064 nm over that at 808 nm at their respective safety limits. Model deep‐tissue cancer PTT at a tissue depth of 5 mm validates the enhanced antitumor effect of SPN_I‐II when shifting laser irradiation from the NIR‐I to the NIR‐II window. The good biodistribution and facile synthesis of SPN_I‐II also allow it to be doped with an NIR dye for fluorescence‐imaging‐guided NIR‐II PTT through systemic administration. Thus, this study paves the way for the development of new polymeric nanomaterials to advance phototherapy.     

Photothermal Control of Heat‐Shock Protein Expression at the Single Cell Level

Laser heating of individual cells in culture recently led to seminal studies in cell poration, fusion, migration, or nanosurgery, although measuring the local temperature increase in such experiments remains a challenge. Here, the laser‐induced dynamical control of the heat‐shock response is demonstrated at the single cell level, enabled by the use of light‐absorbing gold nanoparticles as nanosources of heat and a temperature mapping technique based on quadriwave lateral shearing interferometry (QLSI) measurements. As it is label‐free, this approach does not suffer from artifacts inherent to previously reported fluorescence‐based temperature‐mapping techniques and enables the use of any standard fluorescent labels to monitor in parallel the cell's response.     

Functionalized Graphene@Gold Nanostar/Lipid for Pancreatic Cancer Gene and Photothermal Synergistic Therapy under Photoacoustic/Photothermal Imaging Dual‐Modal Guidance

Nanomaterial‐based pancreatic cancer treatment has received widespread attention and rapid development in the past few years. The major challenges include the poor combination of diagnosis and therapy, the difficulty in targeting therapy from the root and the unsatisfactory antitumor efficiency, which is accompanied by a great risk of relapse and metastasis. In this work, a positively charged lipid bilayer membrane is coated on reduced graphene oxide@gold nanostar (rGO@AuNS) for photoacoustic/photothermal dual‐modal imaging‐guided gene/photothermal synergistic therapy of pancreatic cancer. In addition, the cross‐linking of folic acid on the surface of rGO@AuNS‐lipid can specifically bind after recognizing folic acid receptors on the surface of cancer cells, and greatly improve the targeting ability of the nanomaterial and the performance of imaging diagnosis by receptor‐mediated endocytosis. Moreover, the photothermal and gene (targeting G12V mutant K‐Ras gene) synergistic therapy shows outstanding anticancer efficacy for pancreatic cancer tumor bearing mice, and it is noteworthy that the treatment groups have anti‐liver metastasis of pancreatic cancer.     

Trifolium‐like Platinum Nanoparticle‐Mediated Photothermal Therapy Inhibits Tumor Growth and Osteolysis in a Bone Metastasis Model

Bone metastasis is a frequent and fatal complication of cancer that lacks effective clinical treatment. Photothermal therapy represents a new strategy for the destruction of multiple cancers. In this study, trifolium‐like platinum nanoparticles (TPNs) with small size and excellent photothermal conversion property are prepared via a facile and green method. TPNs show minimal cytotoxicity on normal cell lines and kill cancer cells upon exposure to a near‐infrared light. These nanoparticles effectively inhibit tumor growth and prevent osteolysis in a bone metastasis model. This study offers a promising strategy in the treatment of bone metastasis.     

Pd Nanosheet‐Covered Hollow Mesoporous Silica Nanoparticles as a Platform for the Chemo‐Photothermal Treatment of Cancer Cells

A versatile system combining chemotherapy with photothermal therapy for cancer cells using Pd nanosheet‐covered hollow mesoporous silica nanoparticles is reported. While the hollow mesoporous silica core can be used to load anticancer drugs (i.e., doxorubicin) for chemotherapy, the Pd nanosheets on the surface of particles can convert NIR light into heat for photothermal therapy. More importantly, the loading of Pd nanosheets on hollow mesoporous silica nanospheres can dramatically increase the amount of cellular internalization of the Pd nanosheets: almost 11 times higher than the unloaded Pd nanosheets. The as‐prepared nanocomposites efficiently deliver both drugs and heat to cancer cells to improve the therapeutic efficiency with minimal side effects. Compared with chemotherapy or photothermal therapy alone, the combination of chemotherapy and phototherapy can significantly improve the therapeutic efficacy, exhibiting a synergistic effect.     

A Porphyrin‐Based Conjugated Polymer for Highly Efficient In Vitro and In Vivo Photothermal Therapy

Conjugated polymers have been increasingly studied for photothermal therapy (PTT) because of their merits including large absorption coefficient, facile tuning of exciton energy dissipation through nonradiative decay, and good therapeutic efficacy. The high photothermal conversion efficiency (PCE) is the key to realize efficient PTT. Herein, a donor–acceptor (D–A) structured porphyrin‐containing conjugated polymer (PorCP) is reported for efficient PTT in vitro and in vivo. The D–A structure introduces intramolecular charge transfer along the backbone, resulting in redshifted Q band, broadened absorption, and increased extinction coefficient as compared to the state‐of‐art porphyrin‐based photothermal reagent. Through nanoencapsulation, the dense packing of a large number of PorCP molecules in a single nanoparticle (NP) leads to favorable nonradiative decay, good photostability, and high extinction coefficient of 4.23 × 10⁴m ^?1 cm^?1 at 800 nm based on porphyrin molar concentration and the highest PCE of 63.8% among conjugated polymer NPs. With the aid of coloaded fluorescent conjugated polymer, the cellular uptake and distribution of the PorCP in vitro can be clearly visualized, which also shows effective photothermal tumor ablation in vitro and in vivo. This research indicates a new design route of conjugated polymer‐based photothermal therapeutic materials for potential personalized theranostic nanomedicine.     

Novel Magnetic‐Luminescent Janus Nanoparticles for Cell Labeling and Tumor Photothermal Therapy

Magnetic‐luminescent nanocomposites have multiple uses including multimodal imaging, magnetic targeted drug delivery, and cancer imaging‐guided therapies. In this work, dumbbell‐like MnFe₂O₄–NaYF₄ Janus nanoparticles are synthesized via a two‐step thermolysis approach. These synthesized nanoparticles exhibit stability in aqueous solutions and very low cytotoxicity after poly(acryl amide) modification. High cellular uptake efficiency is observed for the folic acid‐conjugated MnFe₂O₄–NaYF₄ in human esophagus carcinoma cells (Eca‐109) due to the upconversion luminescence properties as well as the folate targeting potential. The MnFe₂O₄–NaYF₄ also strongly absorbs light in the near‐infrared range and rapidly converts to heat energy. It is demonstrated that Eca‐109 cells incubated with MnFe₂O₄–NaYF₄ are killed with high efficiency after 808 nm laser irradiation. Furthermore, the growth of tumors in mice (grown from Eca‐109 cells) is highly inhibited by the photothermal effects of MnFe₂O₄–NaYF₄ efficiently. Histological analysis reveals no pathological change and inflammatory response in heart, liver, spleen, lung, or kidney. The low toxicity, excellent luminescence, and highly efficient photothermal therapy properties of MnFe₂O₄–NaYF₄ Janus nanoparticles illustrated in this work support their vast potential for nanomedicine and cancer therapy.     

Defective Porous Carbon Polyhedra Decorated with Copper Nanoparticles for Enhanced NIR‐Driven Photothermal Cancer Therapy

Currently, there is tremendous interest in the discovery of new and improved photothermal agents for near‐infrared (NIR)‐driven cancer therapy. Herein, a series of novel photothermal agents, comprising copper nanoparticles supported on defective porous carbon polyhedra are successfully prepared by heating a Cu‐BTC metal–organic framework (MOF) precursor at different temperatures (t) in the range 400–900 °C under an argon atmosphere. The copper nanoparticle size and carbon defect concentration in the obtained products (denoted herein as Cu@CPP‐t) increase with synthesis temperature, thus imparting the Cu@CPP‐t samples with distinct NIR absorption properties and photothermal heating responses. The Cu@CPP‐800 sample shows a remarkable photothermal conversion efficiency of 48.5% under 808 nm laser irradiation, representing one of the highest photothermal efficiencies yet reported for a carbon‐based photothermal agent. In vivo experiments conducted with tumor bearing nude Balb/c mice confirm the efficacy of Cu@CPP‐800 as a very promising NIR‐driven phototherapy agent for cancer treatment. Results encourage the wider use of MOFs as low cost precursors for the synthesis of carbon‐supported metal nanoparticle composites for photothermal therapy.     

Multifunctional Conjugated Polymer Nanoparticles for Image‐Guided Photodynamic and Photothermal Therapy

A multifunctional theranostic platform based on conjugated polymer nanoparticles (CPNs) with tumor targeting, fluorescence detection, photodynamic therapy (PDT), and photothermal therapy (PTT) is developed for effective cancer imaging and therapy. Two conjugated polymers, poly[9,9‐bis(2‐(2‐(2‐methoxyethoxy)ethoxy)‐ethyl)fluorenyldivinylene]‐alt‐4,7‐(2,1,3‐benzothiadiazole) with bright red emission and photosensitizing ability and poly[(4,4,9,9‐tetrakis(4‐(octyloxy)phenyl)‐4,9‐dihydro‐s‐indacenol‐dithiophene‐2,7‐diyl)‐alt‐co‐4,9‐bis(thiophen‐2‐yl)‐6,7‐bis(4‐(hexyloxy)phenyl)‐thiadiazolo‐quinoxaline] with strong near‐infrared absorption and excellent photothermal conversion ability are co‐loaded into one single CPN via encapsulation approach using lipid‐polyethylene glycol as the matrix. The obtained co‐loaded CPNs show sizes of around 30 nm with a high singlet oxygen quantum yield of 60.4% and an effective photothermal conversion efficiency of 47.6%. The CPN surface is further decorated with anti‐HER2 affibody, which bestows the resultant anti‐HER2‐CPNs superior selectivity toward tumor cells with HER2 overexpression both in vitro and in vivo. Under light irradiation, the PDT and PTT show synergistic therapeutic efficacy, which provides new opportunities for the development of multifunctional biocompatible organic materials in cancer therapy.     

Self‐Assembled Peptide‐ and Protein‐Based Nanomaterials for Antitumor Photodynamic and Photothermal Therapy

Tremendous interest in self‐assembly of peptides and proteins towards functional nanomaterials has been inspired by naturally evolving self‐assembly in biological construction of multiple and sophisticated protein architectures in organisms. Self‐assembled peptide and protein nanoarchitectures are excellent promising candidates for facilitating biomedical applications due to their advantages of structural, mechanical, and functional diversity and high biocompability and biodegradability. Here, this review focuses on the self‐assembly of peptides and proteins for fabrication of phototherapeutic nanomaterials for antitumor photodynamic and photothermal therapy, with emphasis on building blocks, non‐covalent interactions, strategies, and the nanoarchitectures of self‐assembly. The exciting antitumor activities achieved by these phototherapeutic nanomaterials are also discussed in‐depth, along with the relationships between their specific nanoarchitectures and their unique properties, providing an increased understanding of the role of peptide and protein self‐assembly in improving the efficiency of photodynamic and photothermal therapy.     

A Flexible Caterpillar‐Like Gold Nanoparticle Assemblies with Ultrasmall Nanogaps for Enhanced Dual‐Modal Imaging and Photothermal Therapy

Gold nanoparticle (AuNP) assemblies (GNAs) have attracted attention since enhanced coupling plasmonic resonance (CPR) emerged in the nanogap between coupling AuNPs. For one dimensional GNAs (1D‐GNAs), most CPR from the nanogaps could be easily activated by electromagnetic waves and generate drastically enhanced CPR because the nanogaps between coupling AuNPs are linearly distributed in the 1D‐GNAs. The reported studies focus on the synthesis of 1D‐GNAs and fundamental exploration of CPR. There are still problems which impede further applications in nanomedicine, such as big size (>500 nm), poor water solubility, and/or poor stability. In this study, a kind of 1D flexible caterpillar‐like GNAs (CL‐GNAs) with ultrasmall nanogaps, good water solubility, and good stability is developed. The CL‐GNAs have a flexible structure that can randomly move to change their morphology, which is rarely reported. Numerous ultrasmall nanogaps (<1 nm) are linearly distributed along the structure of CL‐GNAs and generate enhanced CPR. The toxicity assessments in vitro and vivo respectively demonstrate that CL‐GNAs have a low cytotoxicity and good biocompatibility. The CL‐GNAs can be used as an efficient photothermal agent for photothermal therapy, a probe for Raman imaging and photothermal imaging.