Hollow Cavity CaO2 @Polydopamine Nanocomposites for pH-Responsive Ca2+ -Enhanced Efficient Mild Hyperthermia in the NIR-II Region.

Second near-infrared (NIR-II) mild photothermal therapy with higher tissue penetration depth and less damage to healthy tissues is emerging as an attractive antitumor modality, but its therapeutic efficiency is dramatically suppressed by the resistance of heat shock proteins (HSPs). As a widely explored photothermal agent, the application of polydopamine (PDA) in the NIR-II region is hampered by low photothermal conversion efficiency (PCE). Herein, its PCE in the NIR-II region is improved by developing novel hollow cavity CaO2 @PDA nanocomposites through chelation-induced diffusion of inner core Ca2+ to the shell PDA to facilitate multiple reflections of laser in the cavity. Upon pH-responsive degradation of CaO2 , its structure is transformed into a stacked "nano-mesh" with excellent light absorption and an enlarged effective irradiation area. Overloading of Ca2+ ions not only induces downregulation of HSPs but also enhances interference of light on membrane potential, which further aggravate mitochondrial dysfunction and reduce the thermotolerance of tumor cells, promoting efficient mild hyperthermia of PDA in the NIR-II region.

Cryptotanshinone-Doped Photothermal Synergistic MXene@PDA Nanosheets with Antibacterial and Anti-Inflammatory Properties for Wound Healing.

Humans are threatened by bacteria and other microorganisms, resulting in countless pathogen-related infections and illnesses. Accumulation of reactive oxygen species (ROS) in infected wounds activates strong inflammatory responses. The overuse of antibiotics has led to increasing bacterial resistance. Therefore, effective ROS scavenging and bactericidal capacity are essential and the advanced development of collaborative therapeutic techniques to combat bacterial infections is needed. Here, this work developes an MXene@polydopamine-cryptotanshinone (MXene@PDA-CPT) antibacterial nanosystem with excellent reactive oxygen and nitrogen species scavenging ability, which effectively inactivates drug-resistant bacteria and biofilms, thereby promoting wound healing. In this system, the adhesion of polydopamine nanoparticles to MXene produced a photothermal synergistic effect and free radical scavenging activity, presenting a promising antibacterial and anti-inflammatory strategy. This nanosystem causes fatal damage to bacterial membranes. The loading of cryptotanshinone further expanded the advantages of the system, causing a stronger bacterial killing effect and inflammation mitigatory effect with desired biosafety and biocompatibility. In addition, combining nanomaterials and active ingredients of traditional Chinese medicine, this work provides a new rationale for the future development of wound dressings, which contributes to eliminating bacterial resistance, delaying disease deterioration, and alleviating the pain of patients.

Revealing the Effect of Photothermal Therapy on Human Breast Cancer Cells: A Combined Study from Mechanical Properties to Membrane HSP70.

Hyperthermia-induced overexpression of heat shock protein 70 (HSP70) leads to the thermoresistance of cancer cells and reduces the efficiency of photothermal therapy (PTT). In contrast, cancer cell-specific membrane-associated HSP70 has been proven to activate antitumor immune responses. The dual effect of HSP70 on cancer cells inspires us that in-depth research of membrane HSP70 (mHSP70) during PTT treatment is essential. In this work, a PTT treatment platform for human breast cancer cells (MCF-7 cells) based on a mPEG-NH2-modified polydopamine (PDA)-coated gold nanorod core-shell structure (GNR@PDA-PEG) is developed. Using the force-distance curve-based atomic force microscopy (FD-based AFM), we gain insight into the PTT-induced changes in the morphology, mechanical properties, and mHSP70 expression and distribution of individual MCF-7 cells with high-resolution at the single-cell level. PTT treatment causes pseudopod contraction of MCF-7 cells and generates a high level of intracellular reactive oxygen species, which severely disrupt the cytoskeleton, leading to a decrease in cellular mechanical properties. The adhesion maps, which are recorded by aptamer A8 functional probes using FD-based AFM, reveal that PTT treatment causes a significant upregulation of mHSP70 expression and it starts to exhibit a partial aggregation distribution on the MCF-7 cell surface. This work not only exemplifies that AFM can be a powerful tool for detecting changes in cancer cells during PTT treatment but also provides a better view for targeting mHSP70 for cancer therapy.

Precise Subcellular Organelle Targeting for Boosting Endogenous-Stimuli-Mediated Tumor Therapy.

Though numerous external-stimuli-triggered tumor therapies, including phototherapy, radiotherapy, and sonodynamic therapy have made great progress in cancer therapy, the low penetration depth of the laser, safety concerns of radiation, the therapeutic resistance, and the spatio-temporal constraints of the specific equipment restrict their convenient clinical applications. What is more, the inherent physiological barriers of the tumor microenvironment (TME), including hypoxia, heterogeneity, and high expression of antioxidant molecules also restrict the efficiency of tumor therapy. As a result, the development of nanoplatforms responsive to endogenous stimuli (such as glucose, acidic pH, cellular redox events, and etc.) has attracted great attention for starvation therapy, ion therapy, prodrug-mediated chemotherapy, or enzyme-catalyzed therapy. In addition, nanomedicines can be modified by some targeted units for precisely locating in subcellular organelles and boosting the destroying of tumor tissue, decreasing the dosage of nanoagents, reducing side effects, and enhancing the therapeutic efficiency. Herein, the properties of the TME, the advantages of endogenous stimuli, and the principles of subcellular-organelle-targeted strategies will be emphasized. Some necessary considerations for the exploitation of precision medicine and clinical translation of multifunctional nanomedicines in the future are also pointed out.

Development of Nickel Selenide@polydopamine Nanocomposites for Magnetic Resonance Imaging Guided NIR-II Photothermal Therapy.

The penetration depth of near-infrared laser has greatly restricted the development of most photothermal agents. Recently, photothermal agents in the second near-infrared (NIR-II) window have drawn great attention as they can overcome above barrier. Herein, a novel "all in one" NIR-II responsive nanoplatform (nickel selenide @polydopamine nanocomposites, NiSe@PDA NCs) based on in situ coating the polydopamine (PDA) on the surface of biomineralized nickel selenide nanoparticles (NiSe NPs) for dual-model imaging-guided photothermal therapy is reported. Under the illumination of NIR-II laser (1064 nm), the photothermal conversion efficiency of NiSe@PDA NCs can reach 48.4%, which is higher than that of single NiSe NPs due to the enhanced molar extinction coefficient. In addition, because of the paramagnetic effect of NiSe NPs, the constructed NiSe@PDA NCs can be acted as T1 contrast agent for magnetic resonance imaging (MRI). Most importantly, the MRI contrast effect is enhanced with the coating of PDA layer due to the loose structure of PDA. Ultimately, both in vitro and in vivo experiments demonstrate that the developed NCs can achieve efficient MRI-guided photothermal therapy for treating malignant tumor. Therefore, the designed NiSe@PDA NCs with excellent features show great potential for clinical MRI-guided cancer therapy.

Gram-scale fabrication of Bi@C nanoparticles through one-step hydrothermal method for dual-model imaging-guided NIR-II photothermal therapy.

At present, increasing attention is being paid to photothermal therapy corresponding to the second near infrared (NIR-II) range (1000-1700 nanometers); however, its biomedical applications related to carbon-based nanomaterials (CNMs) have always been limited by the large-scale fabrication of excellent diagnostic probes with a suitable size and optical absorption cross-section. Herein, we successfully prepared Bi@C nanoparticles with a suitable size and high output (3.14 g per patch) through a one-pot hydrothermal method. By combining Bi with carbon, the optical absorption in the NIR-II range was enhanced compared to that for single carbon; moreover, Bi@C could no longer be easily oxidized due to the protection of outer C compared with individual Bi. Furthermore, because of the high atomic number of Bi (Z = 83), the Bi@C nanoparticles exhibited computed imaging contrast properties. According to the in vitro and in vivo experiments, the Bi@C nanoparticles could ablate cancer cells under illumination with a 1064 nm laser with deeper penetration and an appropriate permissible exposure (MPE) to the laser (1 W cm-2), showing excellent performance for the diagnosis and treatment of tumors. This study provides a simple method to synthesize metal-carbon nanocomposites to enhance the NIR-II optical absorption efficiency for effective deep-seated tumor photothermal therapy and will further broaden the applications of CNMs.

Mn-Fe layered double hydroxide nanosheets: a new photothermal nanocarrier for O2-evolving phototherapy.

Iron-manganese layered double hydroxide nanosheets were developed as an effective photothermal nanocarrier for loading a photosensitizer. The catalase-like activity enables the nanosheets to decompose H2O2 into O2, overcoming tumor hypoxia and enhancing O2-dependent photodynamic therapy (PDT). The combination of PDT and photothermal therapy (PTT) can almost completely eliminate tumor tissues.

Photosensitizer-Conjugated Bi2Te3 Nanosheets as Theranostic Agent for Synergistic Photothermal and Photodynamic Therapy.

Phototherapy, including photothermal therapy (PTT)/photodynamic therapy (PDT), is usually considered as a promising strategy for cancer treatment due to its noninvasive and selective therapeutic effect by laser irradiation. A light-activatable nanoplatform based on bovine serum albumin (BSA)-coated Bi2Te3 nanosheets conjugated with methylene blue (MB) was successfully designed and constructed for bimodal PTT/PDT combination therapy. The resultant nanoconstruct (BSA-Bi2Te3/MB) exhibited high stability in various physiological solutions and excellent biocompatibility. Especially, the nanoconstruct not only possessed strong near-infrared absorption and high photothermal conversion as a photothermal agent for efficient tumor ablation but also could successfully load photosensitizer for PDT of tumor. When exposed to laser irradiation, tumors in mice with BSA-Bi2Te3/MB injection were completely eliminated without recurrence within 15 d, demonstrating the potential of the nanoconstruct as a bimodal PTT/PDT therapeutic platform for cancer treatment.

BSA-IrO2 : Catalase-like Nanoparticles with High Photothermal Conversion Efficiency and a High X-ray Absorption Coefficient for Anti-inflammation and Antitumor Theranostics.

Intrinsically integrating precise diagnosis, effective therapy, and self-anti-inflammatory action into a single nanoparticle is attractive for tumor treatment and future clinical application, but still remains a great challenge. In this study, bovine serum albumin-iridium oxide nanoparticles (BSA-IrO2 NPs) with extraordinary photothermal conversion efficiency, good photocatalytic activity, and a high X-ray absorption coefficient were prepared through one-step biomineralization. The nanoparticles allow tumor phototherapy and simultaneous photoacoustic/thermal imaging and computed tomography. More importantly, BSA-IrO2 NPs can also act as a catalase to protect normal cells against H2 O2 -induced reactive oxygen pressure and inflammation while significantly enhancing photoacoustic imaging through microbubble-based inertial cavitation. These remarkable features may open up the exploration iridium-based nanomaterials in theranostics.

BSA-exfoliated WSe2 nanosheets as a photoregulated carrier for synergistic photodynamic/photothermal therapy.

In this study, we present the synthesis and application of a new therapeutic platform based on photosensitizer-loaded, two-dimensional layered nanomaterials of WSe2 for combined photothermal and photodynamic cancer therapy. WSe2 nanosheets are synthesized by a simple and efficient chemical exfoliation using bovine serum albumin (BSA) as an effective exfoliating agent and strong stabilizing agent, endowing the WSe2-BSA nanosheets obtained with high stability in physiological solutions and good biocompatibility without further functionalization. The WSe2-BSA nanosheets can be employed not only as an efficient photothermal agent but also as a carrier to load methylene blue (MB) as a photosensitizing agent for photodynamic therapy. Moreover, the generation of singlet oxygen can be regulated by controlling the release of MB from the WSe2 nanosheets with NIR irradiation. The therapeutic efficacy of the MB-loaded WSe2-BSA (WSe2-BSA/MB) complexes was evaluated in vitro and in vivo. It was found that dual-mode photothermal and photodynamic therapy has a significant synergistic effect and dramatically improves the therapeutic efficacy toward cancer cells compared with single mode treatment. These findings indicate that WSe2 nanosheets could be a promising therapeutic agent and smart carrier for the synergistic combination of phototherapy towards biomedical applications.

Multifunctional PEG-GO/CuS nanocomposites for near-infrared chemo-photothermal therapy.

The synergistic therapy, the combination of photothermal therapy and chemotherapy, has become a potential treatment in the battles with cancer. Here, we developed a synergistic therapy tool that based on CuS nanoparticles-decorated graphene oxide functionalized with polyethylene glycol (PEG-GO/CuS) for cervical cancer treatment. The as-synthesized PEG-GO/CuS nanocomposites with excellent biocompatibility was revealed to have high storage capacity for anticancer drug of doxorubicin (Dox) and high photothermal conversion efficiency, and were effectively employed for the ablation of tumor. In addition, the therapeutic efficacy of Dox-loaded PEG-GO/CuS (PEG-GO/CuS/Dox) nanocomposites was evaluated in vitro and in vivo for cervical cancer therapy. In vitro cell cytotoxicity tests of PEG-GO/CuS/Dox demonstrate about 1.3 and 2.7-fold toxicity than PEG-GO/CuS and free Dox under 5 min irradiation with NIR laser at 1.0 W/cm(2), owing to both PEG-GO/CuS-mediated photothermal ablation and cytotoxicity of light-triggered Dox release. In mouse models, mouse cervical tumor growth was found to be significantly inhibited by the chemo-photothermal effect of PEG-GO/CuS/Dox nanocomposites, resulting in effective tumor reduction. Overall, compared with chemotherapy or photothermal therapy alone, the combined treatment demonstrates better therapeutic efficacy of cancer in vitro and in vivo. These findings highlight the promise of the highly versatile multifunctional nanoparticles in biomedical application.