NIR-II Light-Actuated Nanomotors for Enhanced Photoimmunotherapy Toward Hepatocellular Carcinoma.

Light-propelled nanomotors, which can convert external light into mechanical motion, have shown considerable potential in the construction of a new generation of drug delivery systems. However, the therapeutic efficacy of light-driven nanomotors is always unsatisfactory due to the limited penetration depth of near-infrared-I (NIR-I) light and the inherent biocompatibility of the motor itself. Herein, an asymmetric nanomotor (Pd@ZIF-8/R848@M JNMs) with efficient motion capability is successfully constructed for enhanced photoimmunotherapy toward hepatocellular carcinoma. Under near-infrared-II (NIR-II) irradiation, Pd@ZIF-8/R848@M JNMs convert light energy into heat energy, exhibiting self-thermophoretic locomotion to penetrate deeper into tumor tissues to achieve photothermal therapy. At the same time, functionalized with an immune-activated agent Resiquimod (R848), our nanomotors could convert a "cold tumor" into a "hot tumor", transforming the immunosuppressive microenvironment into an immune-activated state, thus achieving immunotherapy. Dual photoimmunotherapy of the as-developed NIR-II light-driven Pd@ZIF-8/R848@M JNMs demonstrates considerable tumor inhibition effects, offering a promising therapeutic approach in the field of anticancer therapy.

Electrospun medicated gelatin/polycaprolactone Janus fibers for photothermal-chem combined therapy of liver cancer.

Liver cancer is a common cancer in the world, and core-shell nanoparticles as a commonly used combination therapy for local tumor ablation, have many shortcomings. In this study, photothermal Janus nanofibers were prepared using a electrospinning technology for tumor treatment, and the products were characterized and in vitro photothermal performance investigated. The micromorphology analysis showed that the photothermic agent CuS and electrospun fibers (loaded with CuS and anticancer drug dihydromyricetin) were successfully prepared, with diameters of 11.58 ± 0.27 µm and 1.19 ± 0.01 µm, respectively. Water contact angle and tensile test indicated that the fiber membranes has a certain hydrophilic adhesion and excellent mechanical strength. The fiber membranes has 808 nm near-infrared laser photothermal heating performance and photothermal stability, and it also has a strong response to the laser that penetrates biological tissue. In addition, in vitro cell culture and in vivo implantation study showed that the fiber membranes could kill HepG2 hepatocellular carcinoma cells combined with photothermal-chem and could be enriched in the implantation area, respectively. Hence, the Janus membranes may be a potential cancer treatment material.

Evaluation of thermodynamic bioeffects of long-pulsed 1064 nm laser in the photothermal lipolysis.

OBJECTIVES: To evaluate the lipolysis effect of air cooling assisted long-pulsed 1064 laser for improving local adiposity. MATERIALS AND METHODS: The second-level (pulse duration of 0.3-60 s) long-pulsed Nd:YAG 1064 nm laser (LP1064 nm) with or without forced-air cooling was used to irradiate ex-vivo subcutaneous adipose tissue (SAT) of pig or human and in-vivo inguinal fat tissue of Sprague Dawley rats. The temperature of skin surface as well as 5 mm deep SAT was monitored by a plug-in probe thermal couple, and the former was confined to 39°C or 42°C during the treatment. Histological analysis of SAT response was evaluated by SAT sections stained with hematoxylin-eosin and oil red O. Ultra-microstructure changes were examined by transmission electron microscopy. A pilot study on human subject utilizing LP1064 nm laser with air cooling was conducted. The changes in gross abdomen circumference and ultrasonic imaging were studied. RESULTS: Histological examination showed that LP1064 nm laser treatment induced adipocyte injury and hyperthermic lipolysis both in- and ex-vivo. It was also confirmed by clinical practice on patients. By real-time temperature monitoring, we found that in comparison with LP1064 nm laser alone, additional air cooling could increase the temperature difference between epidermis and SAT, promoting heat accumulation deep in fat tissue, as well as providing better protection for epidermis. CONCLUSION: LP1064 nm laser provided reliable adipose tissue thermolysis when the temperature of skin surface was sustained at 39°C or 42°C for 10 min. Application of air-cooling during the laser treatment achieved better effect and safety of photothermal lipolysis. LP1064 nm laser, as a noninvasive device, has comparable thermal lipolysis effect as other common heat-generating devices.

Optimizing the average distance between a blue light photosensitizer and a harmonic nanoparticle for effective infrared photodynamic therapy.

Photodynamic therapy can be significantly improved by techniques utilizing light windows of higher tissue penetration depths with optimally matched photoactive agents to provide deep interstitial treatment. Classical blue light photosensitizers were photodynamically activated using infrared light via coupled harmonic nanoparticles with optimized intermediary distances using spacers. Upon 800 nm pulsed laser irradiation perovskite nanoparticles with optimized coupling to either curcumin or protoporphyrin IX reduced the viability of MCF7 breast cancer cells by 73 percent and 64 percent, respectively, while exhibiting negligible dark toxicity. The findings pave the way for clinical adaptation of ease-of-synthesis photodynamically active preparations operable under deep tissue penetrating infrared lights using commonly available otherwise infrared inactive classical blue light photosensitizers.

Three-dimensional-printed MPBI@ß-TCP scaffold promotes bone regeneration and impedes osteosarcoma under near-infrared laser irradiation.

Beta-tricalcium phosphate (ß-TCP) is considered as one of the most promising biomaterials for bone reconstruction. This study generated a functional molybdenum disulfide (MoS2 )/polydopamine (PDA)/-bone morphogenetic protein 2 (BMP2)-insulin-like growth factor-1 (IGF-1) coating on the ß-TCP scaffold and analyzed the outcomes. The MoS2 /PDA-BMP2-IGF-1@ß-TCP (MPBI@ß-TCP) scaffold was prepared by 3D printing and physical adsorption, followed by characterization to validate its successful construction. The in vitro osteogenic effect of the MPBI@ß-TCP scaffold was evaluated. It was found that MPBI@ß-TCP augmented the adhesion, diffusion and proliferation of mesenchymal stem cells (MSCs). The alkaline phosphatase (ALP) activity, collagen secretion and extracellular matrix (ECM) mineralization along with the expression of Runx2, ALP and OCN were also enhanced in the presence of MPBI@ß-TCP. Additionally, MPBI@ß-TCP stimulated endothelial cells to secrete VEGF and promoted capillary-like tubule formation. We then confirmed the biocompatibility of MPBI@ß-TCP to macrophages and its anti-inflammatory effects. Furthermore, under near-infrared (NIR) laser irradiation, MPBI@ß-TCP produced photothermal effect to not only kill MG-63 osteosarcoma cells, but also enhance bone regeneration in vivo with biosafety. Overall, this work demonstrates that 3D-printed MPBI@ß-TCP with enhanced osteogenic activity under NIR laser irradiation has a vast potential in the field of tissue defects.

Carbohydrate ligands-directed active tumor targeting of combinatorial chemotherapy/phototherapy-based nanomedicine: A review.

Phototherapies or light mediated therapies, including mutually photothermal and photodynamic therapy that encompass irradiation of the target organs with light, have been widely employed as minimally invasive approach associated with negligible drug resistance for eradicating multiple tumors with minimal hazards to normal organs. Despite all these advantages, many obstacles in phototherapy hinder progress toward clinical application. Therefore, researchers have developed nano-particulate delivery systems integrated with phototherapy and therapeutic cytotoxic drugs to overcome these obstacles and achieve maximum efficacy in cancer treatment. Active targeting ligands were integrated into their surfaces to improve the selectivity and tumor targeting ability, enabling easy binding and recognition by cellular receptors overexpressed on the tumor tissue compared to normal ones. This enhances intratumoral accumulation with minimal toxicity on the adjacent normal cells. Various active targeting ligands, including antibodies, aptamers, peptides, lactoferrin, folic acid and carbohydrates, have been explored for the targeted delivery of chemotherapy/phototherapy-based nanomedicine. Among these ligands, carbohydrates have been applied due to their unique features that ameliorate the bioadhesive, noncovalent conjugation to biological tissues. In this review, the up-to-date techniques of employing carbohydrates active targeting ligands will be highlighted concerning the surface modification of the nanoparticles for ameliorating the targeting ability of the chemo/phototherapy.

Synergistic effects of integrin binding peptide (RGD) and photobiomodulation therapies on bone-like microtissues to enhance osteogenic differentiation.

Bone tissue engineering aims to diversify and enhance the strategies for bone regeneration to overcome bone-related health problems. Bone mimetic peptides such as Gly-Arg-Gly-Asp-Ser (RGD) are useful tools for osteogenic differentiation. Similarly, photobiomodulation (PBM) at 600-800 nm of wavelength range improves bone tissue healing via the production of intracellular reactive oxygen species (ROS), ATP synthesis, and nitric oxide (NO) release. Besides, traditional monolayer cell culture models have limited conditions to exhibit the details of a mechanism such as a peptide or PBM therapy. However, scaffold-free microtissues (SFMs) can mimic a tissue more properly and be an efficient way to understand the mechanism of therapy via cell-cell interaction. Thus, the synergistic effects of RGD peptide (1 mM) and PBM applications (1 J/cm2 energy density at 655 nm of wavelength and 5 J/cm2 energy density at 808 nm of wavelength) were evaluated on SFMs formed with the co-culture of Human Bone Marrow Stem Cells (hBMSC) and Human Umbilical Vein Endothelial Cells (HUVEC) for osteogenic differentiation. Cell viability assays, mechanistic analysis, and the evaluation of osteogenic differentiation markers were performed. Combined therapies of RGD and PBM were more successful to induce osteogenic differentiation than single therapies. Especially, RGD + PBM at 655 nm group exhibited a higher capability of osteogenic differentiation via ROS production, ATP synthesis, and NO release. It can be concluded that the concomitant use of RGD and PBM may enhance bone regeneration and become a promising therapeutic tool to heal bone-related problems in clinics.

Effect of near-infrared and blue laser light on vero E6 cells SARS-CoV-2 infection model.

Photobiomodulation therapy (PBMT) employing laser light has been emerging as a safe strategy to challenge viruses. In this study the effect of blue and near-infrared (NIR) laser light was assessed in an in vitro model of SARS-CoV-2 infection. PBMT at blue wavelength inhibited viral amplification when the virus was directly irradiated and then transferred to cell culture and when cells already infected were treated. The NIR wavelength resulted less efficacious showing a minor effect on the reduction of the viral load. The cells receiving the irradiated virus or directly irradiated rescued their viability to level comparable to not treated cells. Virion integrity and antigenicity were preserved after blue and NIR irradiation, suggesting that the PBMT antiviral effect was not correlated to viral lipidic envelope disruption. Our results suggested that PBMT can be considered a valid strategy to counteract SARS-CoV-2 infection, at least in vitro.

Revisiting Transcranial Light Stimulation as a Stroke Therapeutic-Hurdles and Opportunities.

Near-infrared laser therapy, a special form of transcranial light therapy, has been tested as an acute stroke therapy in three large clinical trials. While the NEST trials failed to show the efficacy of light therapy in human stroke patients, there are many lingering questions and lessons that can be learned. In this review, we summarize the putative mechanism of light stimulation in the setting of stroke, highlight barriers, and challenges during the translational process, and evaluate light stimulation parameters, dosages and safety issues, choice of outcomes, effect size, and patient selection criteria. In the end, we propose potential future opportunities with transcranial light stimulation as a cerebroprotective or restorative tool for future stroke treatment.

ß-Cyclodextrin-Based Nanosponges Inclusion Compounds Associated with Gold Nanorods for Potential NIR-II Drug Delivery.

This article describes the synthesis and characterization of two nanocarriers consisting of ß-cyclodextrin-based nanosponges (NSs) inclusion compounds (ICs) and gold nanorods (AuNRs) for potential near-infrared II (NIR-II) drug-delivery systems. These nanosystems sought to improve the stability of two drugs, namely melphalan (MPH) and curcumin (CUR), and to trigger their photothermal release after a laser irradiation stimulus (1064 nm). The inclusion of MPH and CUR inside each NS was confirmed by field emission scanning electron microscopy (FE-SEM), Raman spectroscopy, Fourier transform infrared spectroscopy, (FT-IR) differential scanning calorimetry (DSC), transmission electron microscopy (TEM), and proton nuclear magnetic resonance (1H-NMR). Furthermore, the association of AuNRs with both ICs was confirmed by FE-SEM, energy-dispersive spectroscopy (EDS), TEM, dynamic light scattering (DLS), ζ-potential, and UV-Vis. Moreover, the irradiation assays demonstrated the feasibility of the controlled-photothermal drug release of both MPH and CUR in the second biological window (1000-1300 nm). Finally, MTS assays depicted that the inclusion of MPH and CUR inside the cavities of NSs reduces the effects on mitochondrial activity, as compared to that observed in the free drugs. Overall, these results suggest the use of NSs associated with AuNRs as a potential technology of controlled drug delivery in tumor therapy, since they are efficient and non-toxic materials.

Responses of melanoma cells to photobiomodulation depend on cell pigmentation and light parameters.

Melanoma is a highly aggressive skin cancer that requires new approaches for its management. Low-level laser therapy, currently named photobiomodulation therapy (PBM), has been used to improve different conditions but its effects and safe use on melanoma remain unexplored. Herein, we investigated the PBM impact on melanoma cells differing by pigmentation using near-infrared (NIR) and red lasers in vitro. In vivo, we evaluated the effects of the red laser on melanoma-bearing mice. Amelanotic (SK-MEL-37) and melanotic (B16F10) cells were exposed in vitro to a NIR (780 nm, 40 mW) or a red laser (660 nm, 40 mW) in 3 different light doses: 30, 90, and 150 J/cm2 and responses were assessed regarding mitochondrial activity, invasiveness, migration, and VEGF production. In vivo, melanoma-bearing mice received the red laser delivering 150 J/cm2 directly to the tumor on 3 consecutive days. Mice were monitored for 15 days regarding tumor progression and mouse survival. We noticed that amelanotic cells were unresponsive to NIR light. In contrast, NIR irradiation at 30 J/cm2 promoted an increase in the invasiveness of pigmented cells, even though all light doses have inhibited cell migration. Regarding the red laser on pigmented cells, the highest light dose (150 J/cm2) decreased the VEGF production and migration. In vivo, melanoma-bearing mice treated with red laser showed smaller tumor volume and longer survival than controls. We conclude that PBM appears to be safe for amelanotic non-pigmented melanoma but triggers different responses in melanotic pigmented cells depending on light parameters. Additionally, a high dose of red laser impairs the invasive behavior of melanoma cells, probably due to the decrease in VEGF synthesis, which may have contributed to tumor arrest and increased mouse survival. These findings suggest that red laser therapy could be a new ally in the supportive care of melanoma patients.

MXene-Assisted Ablation of Cells with a Pulsed Near-Infrared Laser.

Innovative therapies are urgently needed to combat cancer. Thermal ablation of tumor cells is a promising minimally invasive treatment option. Infrared light can penetrate human tissues and reach superficial malignancies. MXenes are a class of 2D materials that consist of carbides/nitrides of transition metals. The transverse surface plasmons of MXenes allow for efficient light absorption and light-to-heat conversion, making MXenes promising agents for photothermal therapy (PTT). To date, near-infrared (NIR) light lasers have been used in PTT studies explicitly in a continuous mode. We hypothesized that pulsed NIR lasers have certain advantages for the development of tailored PTT treatment targeting tumor cells. The pulsed lasers offer a wide range of controllable parameters, such as power density, duration of pulses, pulse frequency, and so on. Consequently, they can lower the total energy applied and enable the ablation of tumor cells while sparing adjacent healthy tissues. We show for the first time that a pulsed 1064 nm laser could be employed for selective ablation of cells loaded with Ti3C2Tx MXene. We demonstrate both low toxicity and good biocompatibility of this MXene in vitro, as well as a favorable safety profile based on the experiments in vivo. Furthermore, we analyze the interaction of MXene with cells in several cell lines and discuss possible artifacts of commonly used cellular metabolic assays in experiments with MXenes. Overall, these studies provide a basis for the development of efficient and safe protocols for minimally invasive therapies for certain tumors.

Preparation of responsive nano-adsorbent to near-infrared laser based on tungsten disulfide for bicalutamide extraction in human biological fluids.

Bicalutamide (BLT), a non-steroidal anti-androgen, is widely used in patients with advanced prostate cancer. This study aimed to synthesize a smart modified nano-adsorbent (SMNA) based on tungsten disulfide (WS2) for solid-phase extraction of BLT from human plasma and urine samples. Briefly, we increased drug loading capacity of SMNA through the polymer grafting onto the WS2 nano-sheets. Specifically, poly (N-vinylcaprolactam) as a thermo-sensitive polymer was incorporated into the synthesized polymer networks. SMNA was characterized via TGA, XRD, FE-SEM and FT-IR techniques. The influential variables including pH (6), adsorption temperature (30°C), and contact time (10 min) were carefully optimized. After drug loading process, SMNA was exposed to 808 nm near-infrared light, the shrinkage of the thermo-sensitive polymer took place quickly and the loaded BLT released in a short time of laser irradiation. In the end, the extracted BLT was analyzed with RP-HPLC-UV system (at 270 nm wavelength). The proposed method provided favorable linearity in the range of 0.1-15 µg/mL (R2 ≥ 0.9998), the LOD and LOQ values were obtained 0.01 µg/mL and 0.04 µg/mL, respectively. The mean results of drug recovery (at the three different concentrations) of the spiked BLT in human plasma (92.08%) and urine (94.17%) were satisfactory.

IR792-MCN@ZIF-8-PD-L1 siRNA drug delivery system enhances photothermal immunotherapy for triple-negative breast cancer under near-infrared laser irradiation.

BACKGROUND: Despite extensive investigations on photothermal therapy, the clinical application is restricted due to poor stability, low therapeutic efficacy of photothermal therapy agents and its affinity loss in the multistep synthesis of delivery carriers. To address this, we designed an IR792-MCN@ZIF-8-PD-L1 siRNA (IM@ZP) nanoparticle drug delivery system. IM@ZP was prepared by in situ synthesis and physical adsorption, followed by characterization. Photothermal conversion ability of IM@ZP was assessed by irradiation of near-infrared (NIR) laser, followed by analysis of its effect on 4T1 cell viability, maturation of dendritic cells (DCs) and the secretion of related cytokines in vitro, and the changes of tumor infiltrating T cells and natural killer (NK) cells in vivo. Subcutaneous 4T1 tumor-bearing mouse and lung metastasis models were established to investigate the role of IM@ZP in killing tumor and inhibiting metastasis in vivo. RESULTS: IM@ZP was uniform nanoparticles of 81.67 nm with the characteristic UV absorption peak of IR792, and could effectively adsorb PD-L1 siRNA. Under the irradiation of 808 nm laser, IM@ZP exhibited excellent photothermal performance. IM@ZP could be efficiently uptaken by 4T1 cells, and had high transfection efficiency of PD-L1 siRNA. Upon NIR laser irradiation, IM@ZP effectively killed 4T1 cells, upregulated HSP70 expression, induced DC maturation and increased secretion of TNF-α and IL-6 in vitro. Moreover, in vivo experimental results revealed that IM@ZP enhanced photothermal immunotherapy as shown by promoted tumor infiltrating CD8 + and CD4 + T cells and NK cells, and inhibited tumor growth and lung metastasis. CONCLUSION: Together, biocompatible IM@ZP nanoparticles result in high photothermal immunotherapy efficiency and may have a great potential as a delivery system for sustained cancer therapy.

The synergistic effect of chemo-photothermal therapies in SN-38-loaded gold-nanoshell-based colorectal cancer treatment.

Aim: 7-Ethyl-10-hydroxycamptothecin (SN-38)-loaded gold nanoshells nanoparticles (HSP@Au NPs) were developed for combined chemo-photothermal therapy to treat colorectal cancer. Materials & methods: SN-38-loaded nanoparticles (HSP NPs) were prepared by the lyophilization-hydration method, and then developed into gold nanoshells. The nanoparticles were characterized and assessed for photothermal properties, cytotoxicity and hemocompatibility in vitro. In vivo anticancer activity was tested in a tumor mouse model. Results: The HSP@Au NPs (diameter 186.9 nm, zeta potential 33.4 mV) led to significant cytotoxicity in cancer cells exposed to a near-infrared laser. Moreover, the HSP@Au NP-mediated chemo-photothermal therapy displayed significant tumor growth suppression and disappearance (25% of tumor clearance rate) without adverse side effects in vivo. Conclusion: HSP@Au NPs may be promising in the treatment of colorectal cancer in the future.

Brief exposure of skin to near-infrared laser augments early vaccine responses.

Rapid establishment of herd immunity with vaccination is effective to combat emerging infectious diseases. Although the incorporation of adjuvant and intradermal (ID) injection could augment early responses to the vaccine, the current chemical or biological adjuvants are inappropriate for this purpose with their side effects and high reactogenicity in the skin. Recently, a near-infrared (NIR) laser has been shown to augment the immune response to ID vaccination and could be alternatively used for mass vaccination programs. Here, we determined the effect of NIR laser as well as licensed chemical adjuvants on the immunogenicity 1, 2, and 4 weeks after ID influenza vaccination in mice. The NIR laser adjuvant augmented early antibody responses, while the widely used alum adjuvant induced significantly delayed responses. In addition, the oil-in-water and alum adjuvants, but not the NIR laser, elicited escalated TH2 responses with allergenic immunoglobulin E (IgE) responses. The effect of the NIR laser was significantly suppressed in the basic leucine zipper transcription factor ATF-like 3 (Batf3) knockout mice, suggesting a critical role of the cluster of differentiation 103+ (CD103)+ dendritic cells. The current preliminary study suggests that NIR laser adjuvant is an alternative strategy to chemical and biological agents to timely combat emerging infectious diseases. Moreover, its immunomodulatory property could be used to enhance the efficacy of immunotherapy for allergy and cancer.

Iron Hydroxide/Oxide-Reduced Graphene Oxide Nanocomposite for Dual-Modality Photodynamic and Photothermal Therapy In Vitro and In Vivo.

Minimal invasive phototherapy utilising near-infrared (NIR) laser to generate local reactive oxygen species (ROS) and heat has few associated side effects and is a precise treatment in cancer therapy. However, high-efficiency and safe phototherapeutic tumour agents still need developing. The application of iron hydroxide/oxide immobilised on reduced graphene oxide (FeOxH-rGO) nanocomposites as a therapeutic agent in integration photodynamic cancer therapy (PDT) and photothermal cancer therapy (PTT) was discussed. Under 808 nm NIR irradiation, FeOxH-rGO offers a high ROS generation and light-to-heat conversion efficiency because of its strong NIR absorption. These phototherapeutic effects lead to irreversible damage in FeOxH-rGO-treated T47D cells. Using a tumour-bearing mouse model, NIR ablated the breast tumour effectively in the presence of FeOxH-rGO. The tumour treatment response was evaluated to be 100%. We integrated PDT and PTT into a single nanodevice to facilitate effective cancer therapy. Our FeOxH-rGO, which integrates the merits of FeOxH and rGO, displays an outstanding tumoricidal capacity, suggesting the utilization of this nanocomposites in future medical applications.

Near-infrared light triggered activation of pro-drug combination cancer therapy and induction of immunogenic cell death.

Disulfiram copper complex [Cu(DDC)2] nanoparticles have been explored as promising anticancer agents but with concerns of toxic side effects. To improve tumor specificity and enhance anticancer efficacy, we developed a novel [copper sulfide nanoparticle (CuS NP) + disulfiram prodrug (DQ) micelle + near-infrared (NIR) laser] (CDL) combination therapy. DQ, a reactive oxygen species (ROS)-responsive prodrug, can be selectively activated at the tumor site with elevated ROS to release DDC and form Cu(DDC)2in situ. The CuS NP + NIR laser treatment can effectively increase the intra-tumor ROS levels and efficiently activate the DQ prodrug. The CDL therapy kills cancer cells through multiple mechanisms, including ROS amplification cascade and Cu(DDC)2 chemotherapy. NIR light-triggered tumor-specific "nontoxic-to-toxic" transition can significantly improve the specificity of anticancer effects and reduce systemic toxicity. Also, CDL therapy can effectively induce immunogenic cell death (ICD) and has the potential of eliciting antitumor immunity.

A Near-Infrared Laser-Triggered Size-Shrinkable Nanosystem with In Situ Drug Release for Deep Tumor Penetration.

The development of smart size-tunable drug delivery nanoplatform enables the solving of the paradox of inconsistent size-dependence of high tumor accumulation and deep penetration during its delivery process, thus achieving superior cancer treatment efficacy. Herein, we report a size-shrinkable nanomicelle complex system with an initial size of 101 nm enabling effective retention around the tumor periphery and could destruct to ultrasmall nanomicelles triggered by a near-infrared (NIR) laser to realize the deep tumor penetration. The nanomicelle system is consisted of an upper critical solution temperature (UCST)-type block copolymer poly(acrylamide-acrylonitrile)-polyethylene glycol-lipoic acid (p(AAm-co-AN)-g-PEG-LA) encapsulating gold nanorods. Upon the irradiation of the NIR laser at the tumor site, gold nanorods could convert the light energy to heat energy, realizing the photothermal ablation of superficial tumor tissue. Concurrently, the large micelles split into a cascade of ultrasmall micelles (∼7 nm), which could easily penetrate into the deep site of the tumor and achieve the in situ "on-demand" release of the loaded drug to exert superior combined photothermal-chemotherapy of cancer. By the precise manipulation of laser, the micelle complex system realized the hierarchical killing from the superficial-to-deep tumor and achieved almost complete tumor growth inhibition on the established xenograft liver tumor mice model.

Pnictogen Semimetal (Sb, Bi)-Based Nanomaterials for Cancer Imaging and Therapy: A Materials Perspective.

Innovative multifunctional nanomaterials have attracted tremendous interest in current research by facilitating simultaneous cancer imaging and therapy. Among them, antimony (Sb)- and bismuth (Bi)-based nanoparticles are important species with multifunction to boost cancer theranostic efficacy. Despite the rapid development, the extensive previous work treated Sb- and Bi-based nanoparticles as mutually independent species, and therefore a thorough understanding of their relationship in cancer theranostics was lacking. We propose here that the identical chemical nature of Sb and Bi, being semimetals, provides their derived nanoparticles with inherent multifunction for near-infrared laser-driven and/or X-ray-based cancer imaging and therapy as well as some other imparted functions. An overview of recent progress on Sb- and Bi-based nanoparticles for cancer theranostics is provided to highlight the relationship between chemical nature and multifunction. The understanding of Sb- and Bi-based nanoparticles in this way might shed light on the further design of smart multifunctional nanoparticles for cancer theranostics.