Engineered nanomaterials for synergistic photo-immunotherapy.

Nanomaterial-synergized photodynamic therapy (PDT) and photothermal therapy (PTT), as efficient and non-invasive treatment modalities, have shown significant advantages in fighting different types of cancer. However, neither PTT nor PDT can completely eradicate tumors due to distant metastasis and recurrence of tumors. Recently, photo-immunotherapy have attracted great attention as phototherapy has been reported to participate in immunotherapy by triggering immunogenic cell death (ICD), resulting in the secretion of tumor specific antigen (TSAs) and damage-associated molecular patterns (DAMPs). In particular, emerging interests are biased towards manipulating nanomaterials to form unique drug delivery systems, which are necessary for the combination of phototherapy and immunotherapy to eliminate metastatic tumor cells by promoting the maturation of dendritic cells (DCs) and the infiltration of cytotoxic T lymphocytes (CTLs). This review elaborates on the latest strategies on engineering nanomaterials to enhance the anti-cancer efficiency of synergistic photo-immunotherapy, with emphasis on the activation of anti-tumor immune response, the reversal of tumor immunosuppressive microenvironment (TIME), the regulation of the interaction between immunosuppressive cells and tumor cells, the infiltration of immune cells and improved efficiency of photo-immunotherapy-induced ICD. Current challenges and future opportunities in engineering nanomaterials to modulate synergistic photo-immunotherapy are also discussed.

Multifunctional Mesoporous Polydopamine With Hydrophobic Paclitaxel For Photoacoustic Imaging-Guided Chemo-Photothermal Synergistic Therapy.

BACKGROUND: Chemo-photothermal therapy has attracted intensive attention because of its low side effects and better therapeutic efficiency. Although many photothermal agents have been loaded with chemotherapeutic drugs for chemo-photothermal therapy, their applications are limited by complex synthetic protocols and long-term safety. Therefore, there is significant clinical value in the development of a simple system of biocompatible and biodegradable photothermal nanomaterials with high payloads of chemotherapeutic drugs for chemo-photothermal synergistic therapy. MATERIALS AND METHODS: In this study, PEG-modified polydopamine nanoparticles with mesoporous structure (MPDA-PEG) were successfully obtained by an emulsion-induced interface assembly strategy. Subsequently, paclitaxel (PTX) dissolved in acetone was loaded into the mesoporous channels of MPDA-PEG nanoparticles by solution absorption method. A PTX-loaded MPDA-PEG (MPDA-PEG-PTX) nanoplatform for combination of photothermal therapy (PTT) and chemotherapy was developed. RESULTS: The synthesized MPDA-PEG nanoparticles had a great photothermal effect under near-infrared (NIR) laser irradiation and exhibited an enhanced photothermal effect with the increase of particle size. Meanwhile, MPDA-PEG nanoparticles also had a high payload of PTX, and the PTX release could be greatly accelerated by elevated temperature from photothermal effect. In MTT cytotoxicity assay, A549 cells incubated with MPDA-PEG-PTX under NIR laser irradiation (PTT + chemotherapy group) exhibited better therapeutic effect than single chemotherapy (MPDA-PEG-PTX group) and PTT (MPDA-PEG + Laser group). The synergistic therapeutic effect of MPDA-PEG-PTX with NIR laser irradiation in vivo was further investigated under the guidance of photoacoustic imaging (PAI), tumors of nude mice treated with MPDA-PEG-PTX with NIR laser irradiation were completely eliminated with minimal side effect. CONCLUSION: The MPDA-PEG-PTX nanoplatform is a simple and effective platform which can completely inhibit tumor growth with minimal side effects under NIR irradiation, and it exhibits better therapeutic effect than single chemotherapy and PTT.

Multifunctional nanoplatform for photoacoustic imaging-guided combined therapy enhanced by CO induced ferroptosis.

A multifunctional CO/thermo/chemotherapy nanoplatform is here reported, which is composed of mesoporous carbon nanoparticles (MCN) as near infrared (NIR)-responsive drug carrier, doxorubicin (DOX) as chemotherapeutic drug and triiron dodecacarbonyl (FeCO) as thermosensitive CO prodrug. The nanoplatform could absorb near-infrared (NIR) light and convert it into ample heat to trigger CO release and could also release DOX in the acidic tumor microenvironment. More importantly, the generated CO molecules successfully increase cancer cell sensitivity to chemotherapeutics by the ferroptosis pathway. Subsequently, under the guidance of photoacoustic imaging, the FeCO-DOX@MCN nanoplatform demonstrates high treatment efficacies in vitro and in vivo by combination of chemotherapy, photothermal therapy and gas therapy. This multifunctional platform with excellent antitumor efficacy has great potential in precision cancer therapy.

Erythrocyte-cancer hybrid membrane-camouflaged melanin nanoparticles for enhancing photothermal therapy efficacy in tumors.

Cell membrane coating has emerged as an intriguing biomimetic strategy to endow nanomaterials with functions and properties inherent to source cells for various biomedical applications. Hybrid membrane of different types of cells could be coated onto nanoparticle surface to achieve additional functions. Herein, we fused red blood cell (RBC) membrane together with MCF-7 cell membrane and fabricated an erythrocyte-cancer (RBC-M) hybrid membrane-camouflaged melanin nanoparticle (Melanin@RBC-M) platform for enhancing therapeutic efficacy of photothermal therapy (PTT). The fused RBC-M hybrid membrane vesicles retained both RBC and MCF-7 cell membrane proteins and the resultant Melanin@RBC-M exhibited prolonged blood circulation and homotypic targeting to source MCF-7 cells simultaneously. Interestingly, increasing MCF-7 membrane components in RBC-M significantly enhanced the homotypic targeting function of Melanin@RBC-M while increasing RBC membrane components in RBC-M effectively reduced the cellular uptake of Melanin@RBC-M by macrophages and improved their circulation time in the blood. After intravenous injection into MCF-7 tumor-bearing athymic nude mice, Melanin@RBC-M with 1:1 membrane protein weight ratio of RBC to MCF-7 exhibited significantly higher tumor accumulation and better PTT efficacy compared with other Melanin@RBC-M with different membrane protein weight ratios as well as pristine melanin nanoparticles, due to the optimal balance between prolonged blood circulation and homotypic targeting. In addition, in vitro photoacoustic results revealed that Melanin@RBC-M had a photoacoustic signal enhancement with the increase of nanoparticle size (64 → 148 nm) and the photoacoustic amplitudes increased linearly with nanoparticle concentration at the excitation wavelength ranged from 680 nm to 800 nm, which could be used for quantification of Melanin@RBC-M in vivo. Looking forward, coating hybrid membrane onto nanoparticles could add flexibility and controllability in enhancing nanoparticles functionality and offer new opportunities for biomedical applications.

Metal-Organic Frameworks-Derived Carbon Nanoparticles for Photoacoustic Imaging-Guided Photothermal/Photodynamic Combined Therapy.

Combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has become a promising cancer treatment in recent years. However, their applications are limited by complex synthetic protocols and low efficacy. Hence, optimizing experimental approach and improving the efficiency of phototherapy is the current research focus. In this work, various pyrolysis temperatures and sizes of zeolitic imidazolate framework-8 (ZIF-8) derived carbon nanoparticles (ZCNs) are obtained by a simple direct pyrolysis of the ZIF-8 nanoparticles. Meanwhile, the ZCNs can be used as photothermal agents and photosensitizers to produce heat and reactive oxygen species simultaneously upon near-infrared laser irradiation. Moreover, it is observed that the phototherapy effects and photoacoustic (PA) signal of ZCNs could be enhanced with the increase in the nanoparticle size. Subsequently, guided by PA imaging, the therapeutic effect of ZCNs is investigated on a small animal model, where tumors are entirely eliminated with minimal side effect, demonstrating the high efficacy of the larger size of ZCNs through combination of PTT and PDT. Therefore, it is expected that the ZCN is a simple and highly effective phototherapeutic platform for oncotherapy, and the concept of size-dependent enhanced behavior of phototherapy and PA imaging will be very useful in the development of nanomaterials for cancer therapy.

Red blood cell membrane-camouflaged melanin nanoparticles for enhanced photothermal therapy.

Photothermal therapy (PTT) has represented a promising noninvasive approach for cancer treatment in recent years. However, there still remain challenges in developing non-toxic and biodegradable biomaterials with high photothermal efficiency in vivo. Herein, we explored natural melanin nanoparticles extracted from living cuttlefish as effective photothermal agents and developed red blood cell (RBC) membrane-camouflaged melanin (Melanin@RBC) nanoparticles as a platform for in vivo antitumor PTT. The as-obtained natural melanin nanoparticles demonstrated strong absorption at NIR region, higher photothermal conversion efficiency (∼40%) than synthesized melanin-like polydopamine nanoparticles (∼29%), as well as favorable biocompatibility and biodegradability. It was shown that RBC membrane coating on melanin nanoparticles retained their excellent photothermal property, enhanced their blood retention and effectively improved their accumulation at tumor sites. With the guidance of their inherited photoacoustic imaging capability, optimal accumulation of Melanin@RBC at tumors was achieved around 4 h post intravenous injection. Upon irradiation by an 808-nm laser, the developed Melanin@RBC nanoparticles exhibited significantly higher PTT efficacy than that of bare melanin nanoparticles in A549 tumor-bearing mice. Given that both melanin nanoparticles and RBC membrane are native biomaterials, the developed Melanin@RBC platform could have great potential in clinics for anticancer PTT.

Coordination-Induced Assembly of Intelligent Polysaccharide-Based Phototherapeutic Nanoparticles for Cancer Treatment.

Smart polysaccharide-based anticancer phototherapeutic nanoparticles are prepared via a coordination-induced assembly process. Upon irradiated with a near infrared laser, the nanoparticles are not only able to simultaneously generate reactive oxygen species and hyperthermia that ablate tumors, but also possess tumor microenvironment-responsive off/on near infrared fluorescence and enhancement in photothermal effect, making them promising theranostic platform of cancer.

Mitochondria-Targeting Magnetic Composite Nanoparticles for Enhanced Phototherapy of Cancer.

Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities in current days while the high laser power density demand and low tumor accumulation are key obstacles that have greatly restricted their development. Here, magnetic composite nanoparticles for dual-modal PTT and PDT which have realized enhanced cancer therapeutic effect by mitochondria-targeting are reported. Integrating PTT agent and photosensitizer together, the composite nanoparticles are able to generate heat and reactive oxygen species (ROS) simultaneously upon near infrared (NIR) laser irradiation. After surface modification of targeting ligands, the composite nanoparticles can be selectively delivered to the mitochondria, which amplify the cancer cell apoptosis induced by hyperthermia and the cytotoxic ROS. In this way, better photo therapeutic effects and much higher cytotoxicity are achieved by utilizing the composite nanoparticles than that treated with the same nanoparticles missing mitochondrial targeting unit at a low laser power density. Guided by NIR fluorescence imaging and magnetic resonance imaging, then these results are confirmed in a humanized orthotropic lung cancer model. The composite nanoparticles demonstrate high tumor accumulation and excellent tumor regression with minimal side effect upon NIR laser exposure. Therefore, the mitochondria-targeting composite nanoparticles are expected to be an effective phototherapeutic platform in oncotherapy.