The nonradiative conversion of light energy into heat (photothermal therapy, PTT) or sound energy (photoacoustic imaging, PAI) has been intensively investigated for the treatment and diagnosis of ...cancer, respectively. By taking advantage of nanocarriers, both imaging and therapeutic functions together with enhanced tumour accumulation have been thoroughly studied to improve the pre-clinical efficiency of PAI and PTT. In this review, we first summarize the development of inorganic and organic nano photothermal transduction agents (PTAs) and strategies for improving the PTT outcomes, including applying appropriate laser dosage, guiding the treatment via imaging techniques, developing PTAs with absorption in the second NIR window, increasing photothermal conversion efficiency (PCE), and also increasing the accumulation of PTAs in tumours. Second, we introduce the advantages of combining PTT with other therapies in cancer treatment. Third, the emerging applications of PAI in cancer-related research are exemplified. Finally, the perspectives and challenges of PTT and PAI for combating cancer, especially regarding their clinical translation, are discussed. We believe that PTT and PAI having noteworthy features would become promising next-generation non-invasive cancer theranostic techniques and improve our ability to combat cancers.
Controllable self-assembly of nanoscale building blocks into larger specific structures provides an effective route for the fabrication of new materials with unique optical, electronic, and magnetic ...properties. The ability of nanoparticles (NPs) to self-assemble like molecules is opening new research frontiers in nanoscience and nanotechnology. We present a new class of amphiphilic “colloidal molecules” (ACMs) composed of inorganic NPs tethered with amphiphilic linear block copolymers (BCPs). Driven by the conformational changes of tethered BCP chains, such ACMs can self-assemble into well-defined vesicular and tubular nanostructures comprising a monolayer shell of hexagonally packed NPs in selective solvents. The morphologies and geometries of these assemblies can be controlled by the size of NPs and molecular weight of BCPs. Our approach also allows us to control the interparticle distance, thus fine-tuning the plasmonic properties of the assemblies of metal NPs. This strategy provides a general means to design new building blocks for assembling novel functional materials and devices.
Glucose is a key energy supplier and nutrient for tumor growth. Herein, inspired by the glucose oxidase (GOx)‐assisted conversion of glucose into gluconic acid and toxic H2O2, a novel treatment ...paradigm of starving‐like therapy is developed for significant tumor‐killing effects, more effective than conventional starving therapy by only cutting off the energy supply. Furthermore, the generated acidic H2O2 can oxidize l‐Arginine (l‐Arg) into NO for enhanced gas therapy. By using hollow mesoporous organosilica nanoparticle (HMON) as a biocompatible/biodegradable nanocarrier for the co‐delivery of GOx and l‐Arg, a novel glucose‐responsive nanomedicine (l‐Arg‐HMON‐GOx) has been for the first time constructed for synergistic cancer starving‐like/gas therapy without the need of external excitation, which yields a remarkable H2O2–NO cooperative anticancer effect with minimal adverse effect.
Synergistic therapy: A biocompatible and biodegradable nanomedicine based on glucose oxidase/l‐arginine co‐loaded hollow mesoporous organosilica nanoparticles has been successfully constructed for converting intratumoral glucose into high concentrations of toxic hydrogen peroxide and nitric oxide. An endogenous synergistic cancer therapy for efficient tumor eradication has been developed.
Chemodynamic therapy (CDT) utilizes iron‐initiated Fenton chemistry to destroy tumor cells by converting endogenous H2O2 into the highly toxic hydroxyl radical (.OH). There is a paucity of ...Fenton‐like metal‐based CDT agents. Intracellular glutathione (GSH) with .OH scavenging ability greatly reduces CDT efficacy. A self‐reinforcing CDT nanoagent based on MnO2 is reported that has both Fenton‐like Mn2+ delivery and GSH depletion properties. In the presence of HCO3−, which is abundant in the physiological medium, Mn2+ exerts Fenton‐like activity to generate .OH from H2O2. Upon uptake of MnO2‐coated mesoporous silica nanoparticles (MS@MnO2 NPs) by cancer cells, the MnO2 shell undergoes a redox reaction with GSH to form glutathione disulfide and Mn2+, resulting in GSH depletion‐enhanced CDT. This, together with the GSH‐activated MRI contrast effect and dissociation of MnO2, allows MS@MnO2 NPs to achieve MRI‐monitored chemo–chemodynamic combination therapy.
Self‐reinforcing weapon: The Fenton‐like Mn2+ delivery and glutathione (GSH) depletion abilities of MnO2 allow it to exert enhanced chemodynamic efficacy in cancer treatment. An activatable theranostic platform based on multifunctional MnO2‐coated mesoporous silica nanoparticles (MS@MnO2 NPs) has been developed for MRI‐monitored combination chemotherapy and chemodynamic therapy (CDT). ADS=antioxidant defense system.
Biocatalytic reactions in living cells involve complex transformations in the spatially confined microenvironments. Inspired by biological transformation processes, we demonstrate effective ...biocatalytic cascade driven photodynamic therapy in tumor-bearing mice by the integration of an artificial enzyme (ultrasmall Au nanoparticles) with upconversion nanoparticles (NaYF4@NaYb0.92F4:Er0.08@NaYF4)zirconium/iron porphyrin metal–organic framework core–shell nanoparticles (UMOF NPs) which act as biocatalysts and nanoreactors. The construction of core–shell UMOF NPs are realized by using a unique “solvent-assisted self-assembly” method. The integration of ultrasmall AuNPs on the UMOFs matrix leads to glucose depletion, providing Au-mediated cancer therapy via glucose oxidase like catalytic activity. Meanwhile, the UMOF matrix acts as a near-infrared (NIR) light photon-activated singlet oxygen generator through a continuous supply of oxygen via hydrogen peroxide decomposition upon irradiation. Such kinds of biocatalysts offer exciting opportunities for biomedical, catalytical ,and energy applications.
Cancer is one of the leading causes of morbidity and mortality in the world, but more cancer therapies are needed to complement existing regimens due to problems of existing cancer therapies. Herein, ...we term ferroptosis therapy (FT) as a form of cancer therapy and hypothesize that the FT efficacy can be significantly improved via accelerating the Fenton reaction by simultaneously increasing the local concentrations of all reactants (Fe2+, Fe3+, and H2O2) in cancer cells. Thus, Fenton-reaction-acceleratable magnetic nanoparticles, i.e., cisplatin (CDDP)-loaded Fe3O4/Gd2O3 hybrid nanoparticles with conjugation of lactoferrin (LF) and RGD dimer (RGD2) (FeGd-HN@Pt@LF/RGD2), were exploited in this study for FT of orthotopic brain tumors. FeGd-HN@Pt@LF/RGD2 nanoparticles were able to cross the blood–brain barrier because of its small size (6.6 nm) and LF-receptor-mediated transcytosis. FeGd-HN@Pt@LF/RGD2 can be internalized into cancer cells by integrin αvβ3-mediated endocytosis and then release Fe2+, Fe3+, and CDDP upon endosomal uptake and degradation. Fe2+ and Fe3+ can directly participate in the Fenton reaction, whereas the CDDP can indirectly produce H2O2 to further accelerate the Fenton reaction. The acceleration of Fenton reaction generates reactive oxygen species to induce cancer cell death. FeGd-HN@Pt@LF/RGD2 successfully delivered reactants involved in the Fenton reaction to the tumor site and led to significant inhibition of tumor growth. Finally, the intrinsic magnetic resonance imaging (MRI) capability of the nanoparticles was used to assess and monitor tumor response to FT (self-MRI monitoring).
It is essential to control the size and morphology of nanoparticles strictly in nanomedicine. Protein cages offer significant potential for templated synthesis of inorganic nanoparticles. In this ...study, we successfully synthesized ultrasmall copper sulfide (CuS) nanoparticles inside the cavity of ferritin (Fn) nanocages by a biomimetic synthesis method. The uniform CuS–Fn nanocages (CuS–Fn NCs) showed strong near-infrared absorbance and high photothermal conversion efficiency. In quantitative ratiometric photoacoustic imaging (PAI), the CuS–Fn NCs exhibited superior photoacoustic tomography improvements for real-time in vivo PAI of entire tumors. With the incorporation of radionuclide 64Cu, 64CuS–Fn NCs also served as an excellent PET imaging agent with higher tumor accumulation compared to free copper. Following the guidance of PAI and PET, CuS–Fn NCs were applied in photothermal therapy to achieve superior cancer therapeutic efficiency with good biocompatibility both in vitro and in vivo. The results demonstrate that the bioinspired multifunctional CuS–Fn NCs have potential as clinically translatable cancer theranostics and could provide a noninvasive, highly sensitive, and quantitative in vivo guiding method for cancer photothermal therapies in experimental and clinical settings.
Enzyme-based colorimetric assays have been widely used in research laboratories and clinical diagnosis for decades. Nevertheless, as constrained by the performance of enzymes, their detection ...sensitivity has not been substantially improved in recent years, which inhibits many critical applications such as early detection of cancers. In this work, we demonstrate an enzyme-free signal amplification technique, based on gold vesicles encapsulated with Pd–Ir nanoparticles as peroxidase mimics, for colorimetric assay of disease biomarkers with significantly enhanced sensitivity. This technique overcomes the intrinsic limitations of enzymes, thanks to the superior catalytic efficiency of peroxidase mimics and the efficient loading and release of these mimics. Using human prostate surface antigen as a model biomarker, we demonstrated that the enzyme-free assay could reach a limit of detection at the femtogram/mL level, which is over 103-fold lower than that of conventional enzyme-based assay when the same antibodies and similar procedure were used.
Nanomedicines that co-deliver DNA, RNA, and peptide therapeutics are highly desirable yet remain underdeveloped for cancer theranostics. Herein, we report self-assembled intertwining DNA-RNA ...nanocapsules (iDR-NCs) that efficiently delivered synergistic DNA CpG and short hairpin RNA (shRNA) adjuvants, as well as tumor-specific peptide neoantigens into antigen presenting cells (APCs) in lymph nodes for cancer immunotherapy. These nanovaccines were prepared by (1) producing tandem CpG and shRNA via concurrent rolling circle replication and rolling circle transcription, (2) self-assembling CpG and shRNA into DNA-RNA microflowers, (3) shrinking microflowers into iDR-NCs using PEG-grafted cationic polypeptides, and (4) physically loading neoantigen into iDR-NCs. CpG and shRNA in iDR-NCs synergistically activate APCs for sustained antigen presentation. Remarkably, iDR-NC/neoantigen nanovaccines elicit 8-fold more frequent neoantigen-specific peripheral CD8
T cells than CpG, induce T cell memory, and significantly inhibit the progression of neoantigen-specific colorectal tumors. Collectively, iDR-NCs represent potential DNA/RNA/peptide triple-co-delivery nanocarriers and synergistic tumor immunotherapeutic nanovaccines.
Integration of magnetic resonance imaging (MRI) and other imaging modalities is promising to furnish complementary information for accurate cancer diagnosis and imaging‐guided therapy. However, most ...gadolinium (Gd)–chelator MR contrast agents are limited by their relatively low relaxivity and high risk of released‐Gd‐ions‐associated toxicity. Herein, a radionuclide‐64Cu‐labeled doxorubicin‐loaded polydopamine (PDA)–gadolinium‐metallofullerene core–satellite nanotheranostic agent (denoted as CDPGM) is developed for MR/photoacoustic (PA)/positron emission tomography (PET) multimodal imaging‐guided combination cancer therapy. In this system, the near‐infrared (NIR)‐absorbing PDA acts as a platform for the assembly of different moieties; Gd3N@C80, a kind of gadolinium metallofullerene with three Gd ions in one carbon cage, acts as a satellite anchoring on the surface of PDA. The as‐prepared CDPGM NPs show good biocompatibility, strong NIR absorption, high relaxivity (r
1 = 14.06 mM−1 s−1), low risk of release of Gd ions, and NIR‐triggered drug release. In vivo MR/PA/PET multimodal imaging confirms effective tumor accumulation of the CDPGM NPs. Moreover, upon NIR laser irradiation, the tumor is completely eliminated with combined chemo‐photothermal therapy. These results suggest that the CDPGM NPs hold great promise for cancer theranostics.
A versatile cancer theranostic agent, with good biocompatibility, high relaxivity, low risk of release of Gd ions, and near‐infrared‐triggered drug release, is developed based on core–satellite polydopamine–gadolinium metallofullerene, for magnetic resonance/photoacoustic/positron emission tomography multimodal imaging and chemo‐photothermal combination therapy.
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