CRISPR-Cas and CRISPR-based screening system for precise gene editing and targeted cancer therapy.

Target cancer therapy has been developed for clinical cancer treatment based on the discovery of CRISPR (clustered regularly interspaced short palindromic repeat) -Cas system. This forefront and cutting-edge scientific technique improves the cancer research into molecular level and is currently widely utilized in genetic investigation and clinical precision cancer therapy. In this review, we summarized the genetic modification by CRISPR/Cas and CRISPR screening system, discussed key components for successful CRISPR screening, including Cas enzymes, guide RNA (gRNA) libraries, target cells or organs. Furthermore, we focused on the application for CAR-T cell therapy, drug target, drug screening, or drug selection in both ex vivo and in vivo with CRISPR screening system. In addition, we elucidated the advantages and potential obstacles of CRISPR system in precision clinical medicine and described the prospects for future genetic therapy.In summary, we provide a comprehensive and practical perspective on the development of CRISPR/Cas and CRISPR screening system for the treatment of cancer defects, aiming to further improve the precision and accuracy for clinical treatment and individualized gene therapy.

Laser-Ignited Lipid Peroxidation Nanoamplifiers for Strengthening Tumor Photodynamic Therapy Through Aggravating Ferroptotic Propagation and Sustainable High Immunogenicity.

Photodynamic therapy (PDT) is extensively investigated for tumor therapy in the clinic. However, the efficacy of PDT is severely limited by the tissue penetrability of light, short effective half-life and radius of reactive oxygen species (ROS), and the weak immunostimulatory effect. In this study, a glutathione (GSH)-activatable nano-photosensitizer is developed to load with arachidonic acid (AA) and camouflage by erythrocyte membrane, which serves as a laser-ignited lipid peroxidation nanoamplifier (MAR). The photosensitive effect of MAR is recovered accompanied by the degradation in the tumor microenvironment and triggers the peroxidation of AA upon laser excitation. Interestingly, it aggravates the propagation of ferroptosis among cancer cells by driving the continuous lipid peroxidation chain reactions with the participation of the degradation products, ferrous ions (Fe2+), and AA. Consequently, even the deep-seated tumor cells without illumination also undergo ferroptosis owing to the propagation of ferroptotic signal. Moreover, the residual tumor cells undergoing ferroptosis still maintain high immunogenicity after PDT, thus continuously triggering sufficient tumor-associated antigens (TAAs) release to remarkably promote the anti-tumor immune response. Therefore, this study will provide a novel "all-in-one" nano-photosensitizer that not only amplifies the damaging effect and expands the effective range of PDT but also improves the immunostimulatory effect after PDT.

Imaging-Guided Photoacoustic Immunotherapy Based on the Polydopamine-Functionalized Black Phosphorus Nanocomposites.

Phototherapy has great application prospects in superficial tumors, such as melanoma, esophageal cancer, and breast carcinoma, owing to the advantages of noninvasiveness, high spatiotemporal selectivity, and less side effects. However, classical phototherapies including photodynamic and photothermal therapy still need to settle the bottleneck problems of poor efficacy, inevitable thermal damage, and a high rate of postoperative recurrence. In this study, we developed a nanocomposite with excellent optical properties and immune-stimulating properties, termed PBP@CpG, which was obtained by functionalizing black phosphorus (BP) with polydopamine and further adsorbing CpG. Benefiting from the protection of polydopamine against BP, ideal light absorption, and photoacoustic conversion properties, PBP@CpG not only enables precisely delineation of the tumor region with photoacoustic imaging but also powerfully disrupts the plasma membrane and cytoskeleton of tumor cells with a photoacoustic cavitation effect. In addition, we found that the photoacoustic cavitation effect was also capable of inducing immunogenic cell death and remarkably strengthening the antitumor immune response upon cooperating with immune adjuvant CpG. Therefore, PBP@CpG was expected to provide a promising nanoplatform for optical theranostics and herald a new strategy of photoimmunotherapy based on the photoacoustic cavitation effects and immunostimulatory effect.

Cu3P/1-MT Nanocomposites Potentiated Photothermal-Immunotherapy.

Purpose: Photothermal therapy (PTT) is a promising anticancer treatment that involves inducing thermal ablation and enhancing antitumor immune responses. However, it is difficult to completely eradicate tumor foci through thermal ablation alone. Additionally, the PTT elicited antitumor immune responses are often insufficient to prevent tumor recurrence or metastasis, due to the presence of an immunosuppressive microenvironment. Therefore, combining photothermal and immunotherapy is believed to be a more effective treatment approach as it can modulate the immune microenvironment and amplify the post-ablation immune response. Methods: Herein, the indoleamine 2, 3-dioxygenase-1 inhibitors (1-MT) loaded copper (I) phosphide nanocomposites (Cu3P/1-MT NPs) are prepared for PTT and immunotherapy. The thermal variations of the Cu3P/1-MT NPs solution under different conditions were measured. The cellular cytotoxicity and immunogenic cell death (ICD) induction efficiency of Cu3P/1-MT NPs were analyzed by cell counting kit-8 assay and flow cytometry in 4T1 cells. And the immune response and antitumor therapeutic efficacy of Cu3P/1-MT NPs were evaluated in 4T1-tumor bearing mice. Results: Even at low energy of laser irradiation, Cu3P/1-MT NPs remarkably enhanced PTT efficacy and induced immunogenic tumor cell death. Particularly, the tumor-associated antigens (TAAs) could help promote the maturation of dendritic cells (DCs) and antigen presentation, which further activates infiltration of CD8+ T cells through synergistically inhibiting the indoleamine 2, 3-dioxygenase-1. Additionally, Cu3P/1-MT NPs decreased the suppressive immune cells such as regulatory T cells (Tregs) and M2 macrophages, indicating an immune suppression modulation effect. Conclusion: Cu3P/1-MT nanocomposites with excellent photothermal conversion efficiency and immunomodulatory properties were prepared. In addition to enhanced the PTT efficacy and induced immunogenic tumor cell death, it also modulated the immunosuppressive microenvironment. Thereby, this study is expected to offer a practical and convenient approach to amplify the antitumor therapeutic efficiency with photothermal-immunotherapy.

Nanoplatforms Potentiated Ablation-Immune Synergistic Therapy through Improving Local Control and Suppressing Recurrent Metastasis.

Minimally invasive ablation has been widely applied for treatment of various solid tumors, including hepatocellular carcinoma, renal cell carcinoma, breast carcinomas, etc. In addition to removing the primary tumor lesion, ablative techniques are also capable of improving the anti-tumor immune response by inducing immunogenic tumor cell death and modulating the tumor immune microenvironment, which may be of great benefit to inhibit the recurrent metastasis of residual tumor. However, the short-acting activated anti-tumor immunity of post-ablation will rapidly reverse into an immunosuppressive state, and the recurrent metastasis owing to incomplete ablation is closely associated with a dismal prognosis for the patients. In recent years, numerous nanoplatforms have been developed to improve the local ablative effect through enhancing the targeting delivery and combining it with chemotherapy. Particularly, amplifying the anti-tumor immune stimulus signal, modulating the immunosuppressive microenvironment, and improving the anti-tumor immune response with the versatile nanoplatforms have heralded great application prospects for improving the local control and preventing tumor recurrence and distant metastasis. This review discusses recent advances in nanoplatform-potentiated ablation-immune synergistic tumor therapy, focusing on common ablation techniques including radiofrequency, microwave, laser, and high-intensity focused ultrasound ablation, cryoablation, and magnetic hyperthermia ablation, etc. We discuss the advantages and challenges of the corresponding therapies and propose possible directions for future research, which is expected to provide references for improving the traditional ablation efficacy.

Thermoacoustic Imaging-Guided Thermo-Chemotherapy for Hepatocellular Carcinoma Sensitized by a Microwave-Responsive Nitric Oxide Nanogenerator.

Imaging-guided percutaneous microwave thermotherapy has been regarded as an important alternative nonsurgical therapeutic strategy for hepatocellular carcinoma (HCC) that provides excellent local tumor control and favorable survival benefit. However, providing a high-resolution, real-time, and noninvasive imaging technique for intraoperative guidance and controlling postoperative residual tumor recurrence are urgent needs for the clinical setting. In this study, a cisplatin (CDDP)-loaded nanocapsule (NPs@CDDP) with microwave responsive property was prepared to simultaneously serve as a contrast agent of emerging thermoacoustic imaging and a sensitizing agent of microwave thermo-chemotherapy. Accompanying the enzymolysis in the tumor microenvironment, the NPs@CDDP responsively release l-arginine (l-Arg) and CDDP. l-Arg with excellent microwave-absorbing property allowed it to serve as a thermoacoustic imaging contrast agent for accurately delineating the tumor and remarkably increasing tumor temperature under ultralow power microwave irradiation. Apart from the chemotherapeutic effect, CDDP elevated the intracellular H2O2 level through cascade reactions and further accelerated the continuous transformation of l-Arg to nitric oxide (NO), which endowed the NPs@CDDP with NO-generation capability. Notably, the high concentration of intracellular NO was proved to aggravate lipid peroxidation and greatly improved the efficacy of microwave thermo-chemotherapy. Thereby, NPs@CDDP was expected to serve as a theranostic agent integrating the functions of tumor microenvironment-responsive drug delivery system, contrast agent of thermoacoustic imaging, thermal sensitizing agent, and NO nanogenerator, which was promising to provide a potential imaging-guided therapeutic strategy for HCC.

Hydrogen sulfide activatable metal-organic frameworks for Fluorescence Imaging-Guided Photodynamic Therapy of colorectal cancer.

Photodynamic therapy (PDT) is a promising alternative and palliative therapeutic strategy for colorectal cancer (CRC). A novel photosensitizer with higher selectivity for CRC and fewer side effects is vital for clinical application. Given that the overexpression of hydrogen sulfide (H2S) in CRC, it is expected to provide a selective stimulus for activatable photosensitizers that in respond to the specific microenvironment. Herein, we report a novel development of metal-organic frameworks (MOFs) composed of meso-Tetra (4-carboxyphenyl) porphine (TCPP) and ferric ion (Fe3+) through a facile one-pot process. Experiments both in vitro and in vivo reveal that the MOF is capable of depredating in response to the high content of H2S in tumor microenvironment of CRC. Accompanying with the degradation and release of TCPP, the fluorescence and photosensitivity effect is switched from "off" to "on", enabling the MOF to serve as a H2S activatable nano-photosensitizer for real-time fluorescence imaging-guided and targeted PDT of CRC.

Multifunctional Nanosystems Powered Photodynamic Immunotherapy.

Photodynamic Therapy (PDT) with the intrinsic advantages including non-invasiveness, spatiotemporal selectivity, low side-effects, and immune activation ability has been clinically approved for the treatment of head and neck cancer, esophageal cancer, pancreatic cancer, prostate cancer, and esophageal squamous cell carcinoma. Nevertheless, the PDT is only a strategy for local control of primary tumor, that it is hard to remove the residual tumor cells and inhibit the tumor metastasis. Recently, various smart nanomedicine-based strategies are developed to overcome the barriers of traditional PDT including the drawbacks of traditional photosensitizers, limited tissue penetrability of light, inefficient induction of tumor cell death and tumor resistance to the therapy. More notably, a growing number of studies have focused on improving the therapeutic efficiency by eliciting host immune system with versatile nanoplatforms, which heralds a broader clinical application prospect of PDT in the future. Herein, the pathways of PDT induced-tumor destruction, especially the host immune response is summarized, and focusing on the recent progress of nanosystems-enhanced PDT through eliciting innate immunity and adaptive immunity. We expect it will provide some insights for conquering the drawbacks current PDT and expand the range of clinical application through this review.

Tumor Microenvironment-Responsive Nanodrug for Clear-Cell Renal Cell Carcinoma Therapy via Triggering Waterfall-Like Cascade Ferroptosis.

The most common type of kidney tumor, clear-cell renal cell carcinoma (ccRCC) with relatively insidious development and easily metastatic characteristics is generally insensitive to cytotoxic chemotherapy. The abundant polyunsaturated fatty acids (PUFAs) content in advanced ccRCC allows it to be intrinsically vulnerable to ferroptosis-based therapeutic strategies. Nevertheless, the strategy to cause the "iron overload" by administration with iron-based nanomaterials has limited therapeutic efficacy. And the classic ferroptosis agonist (RSL3) with low specificity for tumors, short half-life in the blood, poor water solubility and deficient accumulation at the tumor site prevents its reliable application in vivo. In this study, iron-based metal-organic framework nanoparticles (MIL-101(Fe) NPs) delivered RSL3 to ccRCC tumors, and then released the iron ions and RSL3 accompanied by the degradation of MIL-101(Fe) NPs in the acidic tumor microenvironment. The MIL-101(Fe)@RSL3 as a pH-responsive nanodrug causes cellular iron overload and promotes the hydroxyl radical (•OH) generation by Fenton reaction to attack PUFAs, leading to the aberrant accumulation of lipid peroxides (L-OOH). Additionally, RSL3 directly inhibits glutathione peroxidase 4 (GPX4) to detoxify L-OOH, and ferrous ions further catalyze the irreversible conversion of highly reactive lipid alkoxyl radicals (L-O•) from L-OOH to triggering waterfall-like cascade ferroptosis. In contrast to the limited antitumor efficiency of free RSL3, MIL-101(Fe)@RSL3 with high encapsulation efficiency (88.7%) shows a significant ccRCC-specific antitumor effect and negligible side effects. Taken together, MIL-101(Fe)@RSL3 could aggravate ferroptosis and be expected to be a promising nanodrug for ccRCC systemic therapy due to the targeted delivery and responsive release of RSL3 and iron ions.

Doxorubicin-Loaded Metal-Organic Framework Nanoparticles as Acid-Activatable Hydroxyl Radical Nanogenerators for Enhanced Chemo/Chemodynamic Synergistic Therapy.

Doxorubicin (DOX) is a widely used first-line antitumor agent; however, acquired drug resistance and side effects have become the main challenges to effective cancer therapy. Herein, DOX is loaded into iron-rich metal-organic framework/tannic acid (TA) nanocomplex to form a tumor-targeting and acid-activatable drug delivery system (MOF/TA-DOX, MTD). Under the acidic tumor microenvironment, MTD simultaneously releases DOX and ferrous ion (Fe2+) accompanied by degradation. Apart from the chemotherapeutic effect, DOX elevates the intracellular H2O2 levels through cascade reactions, which will be beneficial to the Fenton reaction between the Fe2+ and H2O2, to persistently produce hydroxyl radicals (•OH). Thus, MTD efficiently mediates chemodynamic therapy (CDT) and remarkably enhances the sensitivity of chemotherapy. More encouragingly, the cancer cell killing efficiency of MTD is up to ~86% even at the ultralow equivalent concentration of DOX (2.26 µg/mL), while the viability of normal cells remained >88% at the same concentration of MTD. Taken together, MTD is expected to serve as drug-delivery nanoplatforms and •OH nanogenerators for improving chemo/chemodynamic synergistic therapy and reducing the toxic side effects.

Carbon-Coated Magnetic Nanoparticle Dedicated to MRI/Photoacoustic Imaging of Tumor in Living Mice.

Multimodality imaging can reveal complementary anatomic and functional information as they exploit different contrast mechanisms, which has broad clinical applications and promises to improve the accuracy of tumor diagnosis. Accordingly, to attain the particular goal, it is critical to exploit multimodal contrast agents. In the present work, we develop novel cobalt core/carbon shell-based nanoparticles (Cobalt at carbon NPs) with both magnetization and light absorption properties for dual-modality magnetic resonance imaging (MRI) and photoacoustic imaging (PAI). The nanoparticle consists of ferromagnetic cobalt particles coated with carbon for biocompatibility and optical absorption. In addition, the prepared Cobalt at carbon NPs are characterized by transmission electron microscope (TEM), visible-near-infrared spectra, Raman spectrum, and X-ray powder diffraction for structural analysis. Experiments verify that Cobalt at carbon NPs have been successfully constructed and the designed Cobalt at carbon NPs can be detected by both MRI and PAI in vitro and in vivo. Importantly, intravenous injection of Cobalt at carbon NPs into glioblastoma-bearing mice led to accumulation and retention of Cobalt at carbon NPs in the tumors. Using such a multifunctional probe, MRI can screen rapidly to identify potential lesion locations, whereas PAI can provide high-resolution morphological structure and quantitative information of the tumor. The Cobalt at carbon NPs are likely to become a promising candidate for dual-modality MRI/PAI of the tumor.

Spherical-matching hyperbolic-array photoacoustic computed tomography.

Linear-array photoacoustic computed tomography (LA-PACT), for its flexibility and simplicity, has great potential in providing anatomical and functional information of tissues. However, the limited coverage view impedes the LA-PACT obtaining high-quality images. In this study, a photoacoustic tomographic system with a hyperbolic-array transducer was developed for stereoscopic PA imaging of carotid artery. The hyperbolic-array PACT increases the receiving sensitivity for PA signal detection due to its transducer's geometric structure matching with the spherical wave. The control phantom experiment shows that the proposed system can expand the angular coverage of ∼1/3 more than that of the LA-PACT system, and the volumetric PA images of rat's carotid artery demonstrates the potential of the system for carotid artery imaging. Furthermore, volumetric imaging of the human forearm verifies that the system has significant capability in human imaging, which indicates that it has bright prospect for assisting diagnosis in the vascular disease.

Dual-Responsive Polyprodrug Nanoparticles with Cascade-Enhanced Magnetic Resonance Signals for Deep-Penetration Drug Release in Tumor Therapy.

Smart transformable nanocarriers are promising to treat deep-seated diseases but require adaptable diagnostic/imaging potency to reflect the morphology change and therapeutic feedback, yet their design and synthesis remains challenging. Herein, stimuli-responsive polyprodrug nanoparticles (SPNs) are formulated from the co-assembly of negatively charged corona and positively charged polyprodrug cores, exhibiting high loading content of camptothecin (CPT, ∼28.6 wt %) tethered via disulfide linkages in the core. SPNs are sequentially sensitive to tumor acidic condition and elevated reductive milieu in the cytosol for deep-penetration drug delivery. Upon accumulation at acidic tumor sites, SPNs dissociate to release smaller positively charged polyprodrug nanoparticles, which efficiently enter deep-seated tumor cells to trigger high-dosage parent CPT release in the reductive cytosolic milieu. Meanwhile, the polyprodrug cores of SPNs labeled with DTPA(Gd), a magnetic resonance imaging contrast agent, can trace the cascade degradation and biodistribution of SPNs as well as the resulting intracellular CPT release. The longitudinal relaxivity of SPNs increases stepwise in the above two processes. The size-switchable polyprodrug nanoparticles exhibit remarkable tumor penetration and noteworthy tumor inhibition in vitro and in vivo, which are promising for endogenously activated precision diagnostics and therapy.

Mitochondrial specific photodynamic therapy by rare-earth nanoparticles mediated near-infrared graphene quantum dots.

Photodynamic therapy (PDT) has been proposed in cancer treatment for decades, but its clinical translation is significantly impeded by the low yield of ROS, poor tissue penetration depth of most current photosensitizers, and short lifetime of ROS. These limitations directly affect the therapeutic effect of PDT in cancer therapy. Here we proposed a new strategy by collaboratively integrating rare-earth doped upconversion nanoparticles (UCNP) with graphene quantum dot (GQD) for highly efficacious PDT, based on the merits of UCNP, which can emit UV-vis light under near-infrared light (NIR) excitation, and GQD, which can produce 1O2 efficiently. For GQD-decorated UCNP nanoparticles (UCNP-GQD), the emission light from UCNP can further excite GQD with prominent 1O2 generation for NIR-triggered PDT. Furthermore, a hydrophilic rhodamine derivative, TRITC, is covalently tethered to afford the resultant UCNP-GQD/TRITC, possessing distinct mitochondrial targeting property. Thus mitochondrial specific PDT with in-situ1O2 burst in mitochondria induces sharp decrease of mitochondrial membrane potential, which initiates the tumor cell apoptosis irreversibly. Importantly, in vivo experiments demonstrate the tumor inhibition of mitochondrial targeting UCNP-GQD/TRITC with improved therapeutic efficiency compared with non-targeting UCNP-GQD. The proposed strategy highlights the advantages of precision organelles-specific PDT in cancer therapy.

Thermoacoustic Imaging and Therapy Guidance based on Ultra-short Pulsed Microwave Pumped Thermoelastic Effect Induced with Superparamagnetic Iron Oxide Nanoparticles.

Multifunctional nanoparticle-mediated imaging and therapeutic techniques are promising modalities for accurate localization and targeted treatment of cancer in clinical settings. Thermoacoustic (TA) imaging is highly sensitive to detect the distribution of water, ions or specific nanoprobes and provides excellent resolution, good contrast and superior tissue penetrability. TA therapy is a potential non-invasive approach for the treatment of deep-seated tumors. In this study, human serum albumin (HSA)-functionalized superparamagnetic iron oxide nanoparticle (HSA-SPIO) is used as a multifunctional nanoprobe with clinical application potential for MRI, TA imaging and treatment of tumor. In addition to be a MRI contrast agent for tumor localization, HSA-SPIO can absorb pulsed microwave energy and transform it into shockwave via the thermoelastic effect. Thereby, the reconstructed TA image by detecting TA signal is expected to be a sensitive and accurate representation of the HSA-SPIO accumulation in tumor. More importantly, owing to the selective retention of HSA-SPIO in tumor tissues and strong TA shockwave at the cellular level, HSA-SPIO induced TA effect under microwave-pulse radiation can be used to highly-efficiently kill cancer cells and inhibit tumor growth. Furthermore, ultra-short pulsed microwave with high excitation efficiency and deep penetrability in biological tissues makes TA therapy a highly-efficient anti-tumor modality on the versatile platform. Overall, HSA-SPIO mediated MRI and TA imaging would offer more comprehensive diagnostic information and enable dynamic visualization of nanoagents in the tumorous tissue thereby tumor-targeted therapy.

Imaging-guided photoacoustic drug release and synergistic chemo-photoacoustic therapy with paclitaxel-containing nanoparticles.

Here, a novel triggered drug release modality was developed for oncotherapy. Paclitaxel (PTX), perfluorohexane (PFH) and gold nanorods (AuNRs) loaded nanoparticles (PTX-PAnP) were synthesized. Folic acid (FA) conjugated PTX-PAnP (PTX-PAnP-FA) could be selectively taken into folate receptor-overexpressed tumor cells. Upon pulsed laser irradiation, the PTX-PAnP-FA could be rapidly destructed because of the PFH vaporization, resulting in fast drug release, which induced apoptosis of cancer cells efficiently. Stimulated fragmentation of the PTX-PAnP-FA nanoparticles can facilitate multiple mechanisms such as bubble implosion, shockwave generation, and sonoporation that further enhance the therapeutic efficiency. The in vivo therapy study further confirmed this new approach resulted in efficient tumor suppression. The results demonstrate a unique drug release mechanism based on photoacoustic effect. It provides an all-in-one platform for photoacoustic image-guided drug release and synergistic chemo-photoacoustic therapy.

Microwave pumped high-efficient thermoacoustic tumor therapy with single wall carbon nanotubes.

The ultra-short pulse microwave could excite to the strong thermoacoustic (TA) shock wave and deeply penetrate in the biological tissues. Based on this, we developed a novel deep-seated tumor therapy modality with mitochondria-targeting single wall carbon nanotubes (SWNTs) as microwave absorbing agents, which act efficiently to convert ultra-short microwave energy into TA shock wave and selectively destroy the targeted mitochondria, thereby inducing apoptosis in cancer cells. After the treatment of SWNTs (40 µg/mL) and ultra-short microwave (40 Hz, 1 min), 77.5% of cancer cells were killed and the vast majority were caused by apoptosis that initiates from mitochondrial damage. The orthotopic liver cancer mice were established as deep-seated tumor model to investigate the anti-tumor effect of mitochondria-targeting TA therapy. The results suggested that TA therapy could effectively inhibit the tumor growth without any observable side effects, while it was difficult to achieve with photothermal or photoacoustic therapy. These discoveries implied the potential application of TA therapy in deep-seated tumor models and should be further tested for development into a promising therapeutic modality for cancer treatment.

Imaging-guided high-efficient photoacoustic tumor therapy with targeting gold nanorods.

Photoacoustic therapy using the large photoacoustic effect of agents for selectively killing cancer cells is demonstrated. Herein, a highly efficient photoacoustic treatment using gold nanorods (AuNRs) and its antitumor effect are reported. Folic acid conjugated AuNRs are designed to specifically target folate receptor-expressing cancer cells. Following photoacoustic treatment, most of the cancer cells with intracellular AuNRs die within 20s. Compared with single-walled carbon nanotubes and indocyanine green containing nanoparticles, AuNRs can produce much stronger shock waves by absorbing the optical energy and thus induced the more efficient cell death at equal molar concentrations. In addition, the laser-induced shock waves can be detected for photoacoustic imaging. Our in vivo experiments demonstrated that the AuNR-mediated photoacoustic treatment resulted in efficient tumor suppression in mice. Thus, both efficient cancer cell diagnostics and selective photoacoustic treatment can be realized with a single-particle formulation. FROM THE CLINICAL EDITOR: Nanotechnology has enabled the development of many novel methods for the treatment of cancer. One of these is photoacoustic therapy. In this article, the authors demonstrated the efficacy of Folic acid conjugated gold nanorods in killing cancer cells after photoacoustic treatment. The findings should provide impetus for future clinical studies.