Oxygen Vacancy Defect Enhanced NIR-II Photothermal Performance of BiOxCl Nanosheets for Combined Phototherapy of Cancer Guided by Multimodal Imaging.

Narrow photo-absorption range and low carrier utilization are significant barriers that restrict the antitumor efficiency of 2D bismuth oxyhalide (BiOX, X = Cl, Br, I) nanosheets (NSs). Introducing oxygen vacancy (OV) defects can expand the absorption range and improve carrier utilization, which are crucial but also challenging. In this study, a series of BiOxCl NSs with different OV defect concentrations (x = 1, 0.7, 0.5) is developed, which shows full spectrum absorption and strong absorption in the second near-infrared region (NIR-II). Density functional theory calculations are utilized to calculate the crystal structure and density states of BiOxCl, which confirm that part of the carriers is separated by OV enhanced internal electric field to improve carrier utilization. The carriers without redox reaction can be trapped in the OV, leading to great majority of photo-generated carriers promoting the photothermal performance. Triggered by single NIR-II (1064 nm), BiOxCl NSs' bidirectional efficient utilization of carriers achieves synchronously combined phototherapy, leading to enhanced tumor ablation and multimodal diagnostic in vitro and vivo. It is thus believed that this work provides an innovative strategy to design and construct nanoplatforms of indirect band gap semiconductors for clinical phototheranostics.

Polydopamine nanomaterials and their potential applications in the treatment of autoimmune diseases.

The conventional treatment methods used for the management of autoimmune diseases (ADs) have limited efficacy and also exhibit significant side effects. Thus, identification of novel strategies to improve the efficacy and safety of ADs treatment is urgently required. Overactivated immune response and oxidative stress are common characteristics associated with ADs. Polydopamine (PDA), as a polymer material with good antioxidant and photothermal conversion properties, has displayed useful application potential against ADs. In addition, PDA possesses good biosafety, simple preparation, and easy functionalization, which is conducive for the pharmacological development of PDA nanomaterials with clinical transformation prospects. Here, we have first reviewed the preparation of PDA, the different functional integration strategies of PDA-based biomaterials, and their potential applications in ADs. Next, the mechanism of action of PDA in ADs has been elaborated in detail. Finally, the application opportunities and challenges linked with PDA nanomaterials for ADs treatment are discussed. This review is contributed to design reasonable and effective PDA nanomaterials for the diagnosis and treatment of ADs.

Gold nanorods with iron oxide dual-modal bioprobes in SERS-MRI enable accurate programmed cell death ligand-1 expression detection in triple-negative breast cancer.

The efficiency of immunotherapy for triple-negative breast cancer (TNBC) is relatively low due to the difficulty in accurately detecting immune checkpoints. The detection of TNBC-related programmed cell death ligand-1 (PD-L1) expression is important to guide immunotherapy and improve treatment efficiency. Surface-enhanced Raman spectroscopy (SERS) and magnetic resonance (MR) imaging exhibit great potential for early TNBC diagnosis. SERS, an optical imaging mode, has the advantages of high detection sensitivity, good spatial resolution, and "fingerprint" spectral characteristics; however, the shallow detection penetration of SERS bioprobes limits its application in vivo. MR has the advantages of allowing deep penetration with no radiation; however, its spatial resolution needs to be improved. SERS and MR have complementary imaging features for tumor marker detection. In this study, gold nanorod and ultrasmall iron oxide nanoparticle composites were developed as dual-modal bioprobes for SERS-MRI to detect PD-L1 expression. Anti-PD-L1 (aPD-L1) was utilized to improve the targeting ability and specificity of PD-L1 expression detection. TNBC cells expressing PD-L1 were accurately detected via the SERS imaging mode in vitro, which can image at the single-cell level. In addition, bioprobe accumulation in PD-L1 expression-related tumor-bearing mice was simply and dynamically monitored and analyzed in vivo using MR and SERS. To the best of our knowledge, this is the first time a SERS-MRI dual-modal bioprobe combined with a PD-L1 antibody has been successfully used to detect PD-L1 expression in TNBC. This work paves the way for the design of high-performance bioprobe-based contrast agents for the clinical immunotherapy of TNBC.

Sequential targeting biomimetic nano platform for enhanced mild photothermal therapy and chemotherapy of tumor.

Tumor targeting drug delivery is of significant importance for the treatment of triple negative breast cancer (TNBC) considering the presence of appreciable amount of tumor matrix and the absence of effective targets on the tumor cells. Hence in this study, a new therapeutic multifunctional nanoplatform with improved TNBC targeting ability and efficacy was constructed and used for therapy of TNBC. Specifically, curcumin loaded mesoporous polydopamine (mPDA/Cur) nanoparticles were synthesized. Thereafter, manganese dioxide (MnO2) and a hybrid of cancer-associated fibroblasts (CAFs) membranes as well as cancer cell membranes were sequentially coated on the surface of mPDA/Cur to obtain mPDA/Cur@M/CM. It was found that two distinct kinds of cell membranes were able to endow the nano platform with homologous targeting ability, thereby achieving accurate delivery of drugs. Nanoparticles gathered in the tumor matrix can loosen the tumor matrix via the photothermal effect mediated by mPDA to rupture the physical barrier of tumor, which is conducive to the penetration and targeting of drugs to tumor cells in the deep tissues. Moreover, the existence of curcumin, MnO2 and mPDA was able to promote the apoptosis of cancer cells by promoting increased cytotoxicity, enhanced Fenton-like reaction, and thermal damage, respectively. Overall, both in vitro and in vivo results showed that the designed biomimetic nanoplatform could significantly inhibit the tumor growth and thus provide an efficient novel therapeutic strategy for TNBC.

Two-dimensional peptide nanosheets functionalized with gold nanorods for photothermal therapy of tumors.

Self-assembled peptide nanomaterials exhibit great potential for applications in materials science, energy storage, nanodevices, analytical science, biomedicine, tissue engineering, and others due to their tailorable ordered nanostructures and unique physical, chemical, and biological properties. Although one-dimensional peptide nanofibers and nanotubes have been widely used for biomedical applications, the design and synthesis of two-dimensional (2D) peptide nanostructures for cancer therapy remain challenging. In this work, we describe the creation of 2D biocompatible peptide nanosheets (PNSs) through molecular self-assembly, which can provide support matrixes for conjugating gold nanorods (AuNRs) to form high-performance 2D nanomaterials for photothermal conversion. After molecular modification, AuNRs can be chemically conjugated onto the surface of 2D PNSs, and the created PNS-AuNR nanohybrids serve as a potential nanoplatform for photothermal therapy of tumor cells. The obtained results indicate that both PNSs and AuNRs contribute to the improved efficiency of photothermal therapy (PTT) of tumors, in which 2D PNSs provide high biocompatibility and a large surface area for binding AuNRs, and AuNRs show a high PTT ability towards tumors. The strategies of molecular design and functional tailoring of self-assembled peptide nanomaterials shown in this study are valuable and inspire the synthesis of biomimetic nanomaterials for biomedicine and tissue engineering applications.

Remediation effects and mechanisms of typical minerals combined with inorganic amendment on cadmium-contaminated soil: a field study in wheat.

The remediation of cadmium (Cd)-contaminated soil has gained much attention recently because Cd in soil threatens human health through the food chain. Although tremendous progress has been made in the remediation of Cd-contaminated soil in rice acid soil system, the mechanism and effects of Cd-contaminated soil remediation under these amendments in wheat weak alkaline soil are still limited. In this study, the remediation effect and related mechanism of Cd in weakly alkaline soil were carried out using zeolite, diatomite, and sodium bentonite as the main remediation components, supplemented by calcium dihydrogen phosphate and fulvic acid. The results of field experiments showed that the concentration of Cd reduced by 27.3 ~ 31.2% in rhizosphere soil and 34.3 ~ 54.2% in non-rhizosphere soil, and the maximum reduction rate of Cd concentration in wheat grain was 25.5%. The main factors affecting the concentration of Cd in wheat grains include the change in exchangeable Cd, the absorption capacity of wheat root, and the inhibitory effect on Cd transport from stem to grain in this paper. In general, this work provides a new potential management feasible pathway to alleviate the Cd toxicity of weakly alkaline soil and wheat grain.

"Double-punch" strategy against triple-negative breast cancer via a synergistic therapy of magneto-mechanical force enhancing NIR-II hypothermal ablation.

Triple-negative breast cancer (TNBC) is a form of breast cancer that is more aggressive and harder to treat than others, with a higher probability of relapse. Its nefarious capabilities for migrating and invading other parts of the body together with the current lack of clinically established effective therapies account for a low survival rate. In this work, we demonstrate the in-tandem use of two complementary therapeutic routes to effectively combat TNBC. A versatile magnetic-photothermal converter (MPC) consisting of zinc-doped ferrite nanoparticles and polyethene glycol, is shown to display excellent therapeutic efficiency, being capable to fight TNBC via two distinct routes: magneto-mechanical force (MMF) and near-infrared-II (NIR-II) hypothermal ablation. The combined use of these two complementary and synergistic therapies, which are less aggressive to the human body compared to conventional chemotherapeutic approaches, results in the splendid suppression of TNBC migration and invasion. Remotely controlling the MPCs by an external magnetic field, results in cellular MMF effects that cause direct mechanical destruction to the cancer cell membrane, leading to its necrosis. Furthermore, the MMF disrupts intracellular lysosomes, thereby triggering the release of large amounts of protein hydrolases, which induce intracellular oxidative stress, and accelerate the induction of apoptosis. Complementing the therapeutic approach based on MMF, the excellent photothermal performance of the MPC in the NIR-II region (1064 nm) is exploited to enable effective hypothermal ablation of the tumours, which can be achieved in deep tissue layers. The proposed multifunctional nanocomposites, together with the demonstrated "double-punch" therapeutic approach, hold significant potential to pave the way for future cutting-edge weapons against the dreadful TNBC.

Biomimetic Yolk-Shell Nanocatalysts for Activatable Dual-Modal-Image-Guided Triple-Augmented Chemodynamic Therapy of Cancer.

Fenton reaction-based chemodynamic therapy (CDT), which applies metal ions to convert less active hydrogen peroxide (H2O2) into more harmful hydroxyl peroxide (·OH) for tumor treatment, has attracted increasing interest recently. However, the CDT is substantially hindered by glutathione (GSH) scavenging effect on ·OH, low intracellular H2O2 level, and low reaction rate, resulting in unsatisfactory efficacy. Here, a cancer cell membrane (CM)-camouflaged Au nanorod core/mesoporous MnO2 shell yolk-shell nanocatalyst embedded with glucose oxidase (GOD) and Dox (denoted as AMGDC) is constructed for synergistic triple-augmented CDT and chemotherapy of tumor under MRI/PAI guidance. Benefiting from the homologous adhesion and immune escaping property of the cancer CM, the nanocatalysts can target tumor and gradually accumulate in tumor site. For triple-augmented CDT, first, the MnO2 shell reacts with intratumoral GSH to generate Mn2+ and glutathione disulfide, which achieves Fenton-like ion delivery and weakening of GSH-mediated scavenging effect, leading to GSH depletion-enhanced CDT. Second, the intratumoral glucose can be oxidized to H2O2 and gluconic acid by GOD, achieving supplementary H2O2-enhanced CDT. Next, the AuNRs absorbing in NIR-II elevate the local tumor temperature upon NIR-II laser irradiation, achieving photothermal-enhanced CDT. Dox is rapidly released for adjuvant chemotherapy due to responsive degradation of MnO2 shell. Moreover, GSH-activated PAI/MRI can be used to monitor CDT process. This study provides a great paradigm for enhancing CDT-mediated antitumor efficacy.

Controllable synthesis of layered black bismuth oxidechloride nanosheets and their applications in internal tumor ablation.

The recently emerging bismuth oxyhalide (BiOX) nanomaterials are promising indirect band gap photosensitizer for ultraviolet (UV) light-triggered phototherapy due to their unique layered nanosheet structure. However, the low absorption and poor photothermal conversion efficiency have always impeded their further applications in cancer clinical therapy. Herein, BiOCl rich in oxygen vacancies has been reported to have full-spectrum absorption properties, making it possible to achieve photothermal property under near-infrared laser. Under 808 nm irradiation, the photothermal conversion efficiency of black BiOCl nanosheets (BBNs) is up to 40%. BBNs@PEG can effectively clear primary subcutaneous tumors and prevent recurrence, achieving good synergistic treatment effect. These results not only broke the limitation of UV on the BiOCl material and provided a good template for other semiconductor materials, but also represent a promising approach to fabricate BBN@PEG a novel, potent and multifunctional theranostic platform for precise photothermal therapy and prognostic evaluation.

The strategy of precise targeting and in situ oxygenating for enhanced triple-negative breast cancer chemophototherapy.

The absence of effective therapeutic targets and tumor hypoxia are the main causes of failure in the treatment of triple-negative breast cancer (TNBC). Biomimetic nanotechnology and tumor microenvironment (TME) responsiveness bring hope and opportunity to address this problem. Here, we develop a core membrane nanoplatform (HM/D-I-BL) using hollow mesoporous manganese dioxide (HM) coated with a biomimetic cancer cell membrane for enhanced chemotherapy/phototherapy via the strategy of precise drug delivery and hypoxia amelioration. Cancer cell membrane modification endows HM/D-I-BL with excellent homologous targeting and immune escape performance. Cellular uptake and fluorescence imaging studies confirmed that HM/D-I-BL can be accurately delivered to tumor sites. HM/D-I-BL also features efficient in situ O2 generation in tumors upon laser irradiation, and subsequently enhanced chemotherapy/phototherapy, pointing to its usefulness as a TME-responsive nanozyme to alleviate tumor hypoxia in the presence of H2O2. In addition, HM/D-I-BL showed good fluorescence and magnetic resonance imaging performances, which offers a reliable multimodal image-guided combination tumor therapy for precision theranostics in the future. In general, this intelligent biomimetic nanoplatform with its homotypic tumor targeting, in situ alleviation of tumor hypoxia and synergetic chemophototherapy would open up a new dimension for the precision treatment of TNBC.

Black TiO2 nanoprobe-mediated mild phototherapy reduces intracellular lipid levels in atherosclerotic foam cells via cholesterol regulation pathways instead of apoptosis.

Given that apoptosis increases the risk of plaque rupture, strategies that reduce intracellular lipid levels without killing foam cells are warranted for safe and effective treatment of atherosclerosis. In this study, a mild phototherapy strategy is carried out to achieve the hypothesis. Foam cell-targeted nanoprobes that allow photothermal therapy (PTT) and/or photodynamic therapy (PDT) were prepared by loading hyaluronan and porphine onto black TiO2 nanoparticles. The results showed that when temperatures below 45 °C, PTT alone and PTT + PDT significantly reduced the intracellular lipid burden without inducing evidently apoptosis or necrosis. In contrast, the use of PDT alone resulted in only a slight reduction in lipid levels and induced massive apoptosis or necrosis. The protective effect against apoptosis or necrosis after mild-temperature PTT and PTT + PDT was correlated with the upregulation of heat shock protein 27. Further, mild-temperature PTT and PTT + PDT attenuated intracellular cholesterol biosynthesis and excess cholesterol uptake via the SREBP2/LDLR pathway, and also triggered ABCA1-mediated cholesterol efflux, ultimately inhibiting lipid accumulation in foam cells. Our results offer new insights into the mechanism of lipid regulation in foam cells and indicate that the black TiO2 nanoprobes could allow safer and more effective phototherapy of atherosclerosis.

Reasonable design of NIR AIEgens for fluorescence imaging and effective photothermal/photodynamic cancer therapy.

The development of a multifunctional single molecule phototherapeutic agent with excellent fluorescence imaging, photothermal therapy and photodynamic therapy at the same time is still a challenging task, which mainly arises from the low absorbance of the molecule, and the complexity of energy dissipation and molecular design. Herein, four donor-acceptor (D-A) compounds were synthesized by linking triphenylamine (TPA), thiophene/thieno[3,2-b]thiophene and different cyano acceptor structures. In this design, we propose a molecular design strategy to redshift absorption and increase the molar extinction coefficient (ε) by enhancing electron-withdrawing acceptors and enlarging the π-conjugation plane unit. Due to the twisted structure of TPA, these compounds exhibit aggregation-induced emission (AIE) characteristics. Notably, these AIEgens have long emission wavelengths, excellent photostability, biocompatibility, photothermal stability and singlet oxygen (1O2) generation performance. Among them, the photothermal conversion efficiency of a compound (named TCF-SS-TPA NPs) can reach 84.5%. Cellular internalization and therapy showed that TCF-SS-TPA NPs have good biocompatibility, excellent cell bioimaging and cancer phototherapy capabilities in vitro. This study will stimulate the molecular design of multifunctional phototherapeutics to realize effective synergistic cancer therapy.

Programmed Stimuli-Responsive Carbon Dot-Nanogel Hybrids for Imaging-Guided Enhanced Tumor Phototherapy.

For harmonizing the contradiction of nanotheranostic agents between enhanced tumor accumulation and penetration, efficient cell internalization and fast elimination are key tactics for promoting their clinical applications. Herein, programmed stimuli-responsive poly(N-isopropylacrylamide)-carbon dot (PNIPAM-CD) hybrid nanogels are designed to address the abovementioned conflicts. The enlarged particle size of PNIPAM-CDs enables one to effectively improve their accumulation at tumor sites. Once the hybrid nanogels are docked in tumors and exposed to deep-red-light (660 nm) irradiation, heat and reactive oxygen species (ROS) are generated from the CDs, consequently activating photothermal therapy (PTT) and photodynamic therapy (PDT) effects and meanwhile inducing partial degradation of PNIPAM-CDs for deep tissue penetration. Further, enhanced cellular internalization of the functional components can be achieved owing to the pH-responsive charge reversal and temperature-dependent hydrophilic/hydrophobic conversion characteristics of PNIPAM-CDs. Finally, the overexpressed glutathione (GSH) in tumor cells would trigger further cleavage of the partially degraded hybrid nanogels, which is beneficial for their rapid clearance from the body. This work not only proposed a novel strategy to fabricate nanotheranostic agents using just a single functional component (i.e., the versatile CDs) to simplify the preparation process but also achieved effective delivery of agents into tumor cells by overcoming the multiple biological barriers to enhance therapeutic efficacy and decrease side effects.

Nanoscale covalent organic frameworks: from controlled synthesis to cancer therapy.

Covalent organic frameworks (COFs), as a new type of crystalline porous materials, mainly consist of light-weight elements (H, B, C, N and O) linked by dynamic covalent bonds to form periodical structures of two or three dimensions. As an attribute of their low density, large surface area, and excellent adjustable pore size, COFs show great potential in many fields including energy storage and separation, catalysis, sensing, and biomedicine. However, compared with metal organic frameworks (MOFs), the relatively large size and irregular morphology of COFs affect their biocompatibility and bioavailability in vivo, thus impeding their further biomedical applications. This Review focuses on the controlled design strategies of nanoscale COFs (NCOFs), unique properties of NCOFs for biomedical applications, and recent progress in NCOFs for cancer therapy. In addition, current challenges for the biomedical use of NCOFs and perspectives for further improvements are presented.

Intelligent Pore Switch of Hollow Mesoporous Organosilica Nanoparticles for High Contrast Magnetic Resonance Imaging and Tumor-Specific Chemotherapy.

Hollow mesoporous organosilica nanoparticles (HMONs) are widely considered as a promising drug nanocarrier, but the loaded drugs can easily leak from HMONs, resulting in the considerably decreased drug loading capacity and increased biosafety risk. This study reports the smart use of core/shell Fe3O4/Gd2O3 (FG) hybrid nanoparticles as a gatekeeper to block the pores of HMONs, which can yield an unreported large loading content (up to 20.4%) of DOX. The conjugation of RGD dimer (R2) onto the DOX-loaded HMON with FG capping (D@HMON@FG@R2) allowed for active tumor-targeted delivery. The aggregated FG in D@HMON@FG@R2 could darken the normal tissue surrounding the tumor due to the high r2 value (253.7 mM-1 s-1) and high r2/r1 ratio (19.13), and the intratumorally released FG as a result of reducibility-triggered HMON degradation could brighten the tumor because of the high r1 value (20.1 mM-1 s-1) and low r2/r1 ratio (7.01), which contributed to high contrast magnetic resonance imaging (MRI) for guiding highly efficient tumor-specific DOX release and chemotherapy.

An intelligent tumor microenvironment responsive nanotheranostic agent for T1/T2 dual-modal magnetic resonance imaging-guided and self-augmented photothermal therapy.

Photothermal therapy (PTT), as a promising antineoplastic therapeutic strategy, has been harnessed to restrain tumor growth through near-infrared (NIR) irradiation mediated thermal ablation. Nevertheless, its biological applications are hampered by thermal diffusion and up-regulated heat shock proteins (HSPs). Herein, a versatile nanotheranostic agent is developed via integrating Zn0.2Fe2.8O4 nanoparticles (NPs), polydopamine (PDA), and MnO2 NPs for T1/T2 dual-modal magnetic resonance (MR) imaging-guided and self-augmented PTT. The as-designed Zn0.2Fe2.8O4@PDA@MnO2 NPs adequately serve as a PTT agent to realize effective photothermal conversion and obtain local hyperthermia. Additionally, the Zn0.2Fe2.8O4@PDA@MnO2 NPs can significantly consume overexpressed glutathione (GSH) and generate Mn2+ in the tumor microenvironment (TME), thus destroying redox homeostasis and catalytically generating hydroxyl radicals (˙OH) for HSP suppression and PTT enhancement. Meanwhile, Mn2+ and Zn0.2Fe2.8O4 NPs significantly strengthen T1- and T2-weighted MR contrast for tumor imaging and PTT guidance. Hence, this study offers proof of concept for self-augmented PTT and T1/T2 dual-modal MR imaging for tumor elimination.

Facile synthesis of biocompatible magnetic titania nanorods for T1-magnetic resonance imaging and enhanced phototherapy of cancers.

Cancer treatment has been recently energized by nanomaterials that simultaneously offer diagnostic and therapeutic effects. Among the imaging and treatment modalities in frontline research today, magnetic resonance imaging (MRI) and phototherapy have gained significant interest due to their noninvasiveness among other intriguing benefits. Herein, Fe(iii) was adsorbed on titanium dioxide to develop magnetic Fe-TiO2 nanocomposites (NCs) which leverage the Fe moiety in a double-edge-sword approach to: (i) achieve T1-weighted MRI contrast enhancement, and (ii) improve the well-established photodynamic therapeutic efficacy of TiO2 nanoparticles. Interestingly, the proposed NCs exhibit classic T1 MRI contrast agent properties (r1 = 1.16 mM-1 s-1) that are comparable to those of clinically available contrast agents. Moreover, the NCs induce negligible cytotoxicity in traditional methods and show remarkable support to the proliferation of intestine organoids, an advanced toxicity evaluation system based on three-dimensional organoids, which could benefit their potential safe application for in vivo cancer theranostics. Aided by the Fenton reaction contribution of the Fe component of the Fe-TiO2 NCs, considerable photo-killing of cancer cells is achieved upon UV irradiation at very low (2.5 mW cm-2) intensity in typical cancer PDT. It is therefore expected that this study will guide the engineering of other biocompatible magnetic titania-based nanosystems with multi-faceted properties for biomedical applications.

Arsenene Nanodots with Selective Killing Effects and their Low-Dose Combination with ß-Elemene for Cancer Therapy.

Arsenical drugs have achieved hallmark success in treating patients with acute promyelocytic leukemia, but expanding their clinical utility to solid tumors has proven difficult with the contradiction between the therapeutic efficacy and the systemic toxicity. Here, leveraging efforts from materials science, biocompatible PEGylated arsenene nanodots (AsNDs@PEG) with high monoelemental arsenic purity that can selectively and effectively treat solid tumors are synthesized. The intrinsic selective killing effect of AsNDs@PEG is closely related to high oxidative stress in tumor cells, which leads to an activated valence-change of arsenic (from less toxic As0 to severely toxic oxidation states), followed by decreased superoxide dismutase activity and massive reactive oxygen species (ROS) production. These effects occur selectively within cancer cells, causing mitochondrial damage, cell-cycle arrest, and DNA damage. Moreover, AsNDs@PEG when applied in a multi-drug combination strategy with ß-elemene, a plant-derived anticancer drug, achieves synergistic antitumor outcomes, and its newly discovered on-demand photothermal properties facilitate the elimination of the tumors without recurrence, potentially further expanding its clinical utility. In line of the practicability for a large-scale fabrication and negligible systemic toxicity of AsNDs@PEG (even at high doses and with repetitive administration), a new-concept arsenical drug with high therapeutic efficacy for selective solid tumor therapy is provided.

Metal-Free Organo-Theranostic Nanosystem with High Nitroxide Stability and Loading for Image-Guided Targeted Tumor Therapy.

The desire for all-organic-composed nanoparticles (NPs) of considerable biocompatibility to simultaneously diagnose and treat cancer is undeniably interminable. Heretofore, metal-based agents dominate the landscape of available magnetic resonance imaging (MRI) contrast agents and photothermal therapeutic agents, but with associated metal-specific downsides. Here, an all-organic metal-free nanoprobe, whose appreciable biocompatibility is synergistically contributed by its tetra-organo-components, is developed as a viable alternative to metal-based probes for MRI-guided tumor-targeted photothermal therapy (PTT). This rationally entails a glycol chitosan (GC)-linked polypyrrole (PP) nanoscaffold that provides abundant primary and secondary amino groups for amidation with the carboxyl groups in a nitroxide radical (TEMPO) and folic acid (FA), to obtain GC-PP@TEMPO-FA NPs. Advantageously, the appreciably benign GC-PP@TEMPO-FA features high nitroxide loading (r1 = 1.58 mM-1 s-1) and in vivo nitroxide-reduction resistance, prolonged nitroxide-systemic circulation times, appreciable water dispersibility, potential photodynamic therapeutic and electron paramagnetic resonance imaging capabilities, considerable biocompatibility, and ultimately achieves a 17 h commensurate MRI contrast enhancement. Moreover, its GC component conveys a plethora of PP to tumor sites, where FA-mediated tumor targeting enables substantial NP accumulation with consequential near-complete tumor regression within 16 days in an MRI-guided PTT. The present work therefore promotes the engineering of organic-based metal-free biocompatible NPs in synergism, in furtherance of tumor-targeted image-guided therapy.

Rational design of nanomedicine for photothermal-chemodynamic bimodal cancer therapy.

Given the diversity, complexity, and heterogeneity of persistent tumors, traditional nanoscale monotherapeutic systems suffer from dissatisfactory curative efficiency with incidence of metastasis or relapse. In parallel, the trend of clinical research on the basis of nanomedicines has increasingly shifted from monotherapy toward combinatorial therapy for admirable synergetic performances. In this regard, cutting-edge nanomedicines harnessing photothermal-chemodynamic bimodal therapy (PTT/CDT) have opened up a highly-efficient and relatively-safe cancer theranostic paradigm. Still, the integration of PTT/CDT functional units into one nanomedicine remains a herculean but meaningful task to achieve notable super-additive effects. This review aims to elucidate underlying synergistic interactions of PTT/CDT and highlight intriguing designs of nanomedicines for PTT/CDT including nanomaterial selection, performance optimization, multimodal therapy, visualization strategies, and targeting strategies. Furthermore, an outlook on further improvements of PTT/CDT is provided, emphasizing significant scientific issues that require remediation for clinical translation. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.