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One of the major limitations of current cancer therapy is the inability to destroy tumors with high efficacy and minimal invasiveness. Herein, we developed a proof-of-concept fixed-point "blasting" strategy to destroy the "castle" of tumors and realized efficient interventional photothermal therapy. The "blasting" materials were composed of photothermal nanoparticles (ancient ink nanoparticles, AINP) and a low boiling point phase change agent (perfluoromethylcyclopentane, FMCP). An injectable in situ-forming thermal-responsive hydrogel composed of biodegradable and biocompatible polymers was employed as a carrier to load the AINP and FMCP. The obtained hydrogel system was a flowable aqueous solution at low or room temperature for facile injection; meanwhile, once administered, it rapidly transformed into a fixed gel at a body temperature of about 37 °C. This unique property could effectually fix the AINP and FMCP and thus restrict the destruction region inside the tumor. Subsequently, triggered by second window near-infrared light, the solid tumors were effectively destroyed by a mild photothermal effect and the subsequent gas mechanical damage. We envisage that this fixed-point "blasting" strategy will pave a new way for the next generation of cancer-interventional photothermal therapy.

The use of red blood cell (RBC) membrane coatings has recently been found to be a biomimetic strategy to confer inner core nanomaterials with improved pharmacokinetic profiles by utilizing the intrinsic long blood circulation time of RBCs. Here, we envelope superparamagnetic nanoclusters (MNCs) with RBC membrane ghosts to obtain MNC@RBCs with significantly improved physiological stability compared to that of bare MNCs. After being loaded with near-infrared (NIR) cypate molecules, the as-prepared Cyp-MNC@RBCs show remarkably increased NIR absorbance and resultant efficient photothermal conversion efficacy. By tracking the NIR fluorescence of cypate in an in vivo fluorescence imaging system, we uncover that such Cyp-MNC@RBCs upon intravenous injection show significantly improved tumor-homing capacity as compared to bare cypate-loaded MNCs. A similar result is further evidenced by recording the T 2 -weighted magnetic resonance imaging (MRI) signal of MNCs. Furthermore, upon exposure to 808 nm laser irradiation, the tumors grown on the mice with the intravenous injection of Cyp-MNC@RBCs show a higher temperature increase than the tumors grown on the mice injected with plain MNC@RBCs and thus are significantly suppressed via photothermal ablation. This study presents the preparation of biomimetic Cyp-MNC@RBCs with greatly improved tumor-homing capacity as multifunctional nanotheranostic agents for fluorescence and MRI bimodal imaging-guided cancer photothermal therapy.

Abstract 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. [ABSTRACT FROM AUTHOR]

Abstract 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. [ABSTRACT FROM AUTHOR]

In this study, we reported a strategy to improve delivery efficiency of a long-circulation biomimetic photothermal nanoagent for enhanced photothermal therapy through selectively dilating tumor vasculature. By using a simply nanocoating technology, a biomimetic layer of natural red blood cell (RBC) membranes was camouflaged on the surface of photothermal polypyrrole nanoparticles (PPy@RBC NPs). The erythrocyte-mimicking PPy NPs inherited the immune evasion ability from natural RBC resulting in superior prolonged blood retention time. Additionally, excellent photothermal and photoacoustic imaging functionalities were all retained attributing to PPy NPs cores. To further improve the photothermal outcome, the endothelin A (ET A ) receptor antagonist BQ123 was jointly employed to regulate tumor microenvironment. The BQ123 could induce tumor vascular relaxation and increase blood flow perfusion through modulating an ET-1/ET A transduction pathway and blocking the ET A receptor, whereas the vessel perfusion of normal tissues was not altered. Through our well-designed tactic, the concentration of biomimetic PPy NPs in tumor site was significantly improved when administered systematically. The study documented that the antitumor efficiency of biomimetic PPy NPs combined with specific antagonist BQ123 was particularly prominent and was superior to biomimetic PPy NPs ( P < 0.05) and PEGylated PPy NPs with BQ123 ( P < 0.01), showing that the greatly enhanced photothermal treatment could be achieved with low-dose administration of photothermal agents. Our findings would provide a promising procedure for other similar enhanced photothermal treatment by blocking ET A receptor to dramatically increase the delivery of biomimetic photothermal nanomaterials. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Along with intrinsic magnetic resonance imaging (MRI) advantages, iron oxide nanomaterials capable of photothermal conversion have been reported very recently and have again raised great interest in their designs among biomedical researchers. However, like other inorganic nanomaterials, high macrophage uptake, short blood retention time and unfavorable biodistributions have strongly hampered their applications in vivo . To solve these problems, a rational design of red blood cell (RBC) membrane camouflaged iron oxide magnetic clusters (MNC@RBCs) is presented in this paper. Our data show that by simply introducing an “ultra-stealth” biomimetic coating to iron oxide magnetic nanoclusters (MNCs), MNC@RBCs maintain the imaging and photothermal functionalities inherited from MNCs cores while achieving much lower nonspecific macrophage uptake and dramatically altered fate in vivo . MNC@RBCs with superior prolonged blood retention time, preferred high tumor accumulation and relatively lowered liver biodistribution are demonstrated when injected intravenously in mice, leading to greatly enhanced photothermal therapeutic efficacy by a single treatment without further magnetic force manipulation. Our study illustrates a well prepared integration of MNCs and RBCs, exploiting advantages of both functionalities within a single unit and suggests a promising future for iron-based nanomaterials application in vivo . [ABSTRACT FROM AUTHOR]

The development of cancer photothermal therapies, many of which rely on photothermal agents, has received significant attention in recent years. In this work, various ligands-stabilized magnetite (Fe3O4) particles are fabricated and utilized as a photothermal agents for in vivo tumor-imaging-guided photothermal therapy. Fe3O4 particles stabilized by macromolecular ligands as, e.g. polyethylene glycol (PEG), exhibit a superior and more stable photothermal effect compared to Fe3O4 particles stabilized by small molecules like citrate, due to their stronger ability of antioxidation. In addition, the photothermal effect of Fe3O4 particles is revealed to increase with size, which is attributed to the redshift of Vis-NIR spectra. Fe3O4 particles injected intravenously into mice can be accumulated in the tumor by the application of an external magnetic field, as revealed by magnetic resonance imaging. In vivo photothermal therapy test of PEG-stabilized Fe3O4 further achieves better tumor ablation effect. Overall, this study demonstrates efficient imaging-guided photothermal therapy of cancer that is based on Fe3O4 particles of optimized size and with optimized ligands. It is expected that the ligand-directed and size-dependent photothermal effect will provide more approaches in the design of novel materials. [ABSTRACT FROM AUTHOR]

Abstract: Mesoporous silica-encapsulated gold nanorods (GNRs@mSiO2) have great potential both in photothermal therapy and drug delivery. In this paper, we firstly developed GNRs@mSiO2 as a synergistic therapy tool for delivery heat and drug to the tumorigenic region. We studied the ablation of tumor both in vitro and in vivo by the combination of photothermal therapy and chemotherapy using doxorubicin (DOX)-loaded GNRs@mSiO2. Significantly greater cell killing was observed when A549 cells incubated with DOX-loaded GNRs@mSiO2 were irradiated with near-infrared (NIR) illumination, attributable to both GNRs@mSiO2-mediated photothermal ablation and cytotoxicity of light-triggered DOX release. We then performed in vivo therapy studies and observed a promising tumor treatment. Compared with chemotherapy or photothermal treatment alone, the combined treatment showed a synergistic effect, resulting in higher therapeutic efficacy. Furthermore, the lower systematic toxicity of GNRs@mSiO2 has been validated. [Copyright &y& Elsevier]

Long blood circulation is the basic requirement of advanced drug delivery systems for tumor treatment, which leads to enhanced tumor therapeutic efficiency and reduced side effects. However, the pharmacokinetics of the current nanoparticles in vivo is still unsatisfactory, which leads to limited success to translate nanoparticles into clinical applications. Inspired by the natural cell membrane-coating strategy, a series of zwitterionic polymer membranes are firstly developed and coated onto different kinds of nanoparticles in this work. Intriguingly, the zwitterionic polymer membrane shows stronger protein adsorption resistance and reduced macrophage uptake compared with the corresponding zwitterionic polymer brush or the red blood cell (RBC) membrane, which results in longer blood circulation time and higher tumor accumulation of the coated nanoparticles. Combined with the photothermal effect of model nanoparticles, Fe 3 O 4 , zwitterionic polymer membrane-coated Fe 3 O 4 shows enhanced photothermal therapy (PTT) efficacy on A549 tumors compared with the corresponding zwitterionic polymer brush or RBC membrane-coated Fe 3 O 4. Notably, Fe 3 O 4 coated by carboxybetaine-based biomimic membranes exhibits the ultra-long blood circulation (t 1/2 = 96.0 h) and strongest PTT efficacy compared with those coated by phosphorylcholine-based or sulfobetaine-based biomimic membranes. In addition, the zwitterionic biomimic membrane exhibits rapid glutathione-triggered degradation with the products of low molecular weight (<2000 g mol−1). Therefore, the biodegradable zwitterionic biomimic membrane coating offers a universal platform for the design and application of long-circulating biomedical nanoparticles, which may pave the way for the clinical applications of biomedical nanoparticles in tumor therapy. [ABSTRACT FROM AUTHOR]