Developing
multifunctional and easily prepared nanoplatforms with
integrated different modalities is highly challenging for molecular
imaging. Here, we report the successful transfer of an important molecular
target, melanin, into a novel multimodality imaging nanoplatform.
Melanin is abundantly expressed in melanotic melanomas and thus has
been actively studied as a target for melanoma imaging. In our work,
the multifunctional biopolymer nanoplatform based on ultrasmall (<10
nm) water-soluble melanin nanoparticle (MNP) was developed and showed
unique photoacoustic property and natural binding ability with metal
ions (for example, 64Cu2+, Fe3+).
Therefore, MNP can serve not only as a photoacoustic contrast agent,
but also as a nanoplatform for positron emission tomography (PET)
and magnetic resonance imaging (MRI). Traditional passive nanoplatforms
require complicated and time-consuming processes for prebuilding reporting
moieties or chemical modifications using active groups to integrate
different contrast properties into one entity. In comparison, utilizing
functional biomarker melanin can greatly simplify the building process.
We further conjugated αvβ3 integrins,
cyclic c(RGDfC) peptide, to MNPs to allow for U87MG tumor accumulation
due to its targeting property combined with the enhanced permeability
and retention (EPR) effect. The multimodal properties of MNPs demonstrate
the high potential of endogenous materials with multifunctions as
nanoplatforms for molecular theranostics and clinical translation.
Despite its growing promise in cancer treatment, ferrotherapy has low therapeutic efficacy due to compromised Fenton catalytic efficiency in tumor milieu. We herein report a hybrid semiconducting nanozyme (HSN) with high photothermal conversion efficiency for photoacoustic (PA) imaging-guided second near-infrared photothermal ferrotherapy. HSN comprises an amphiphilic semiconducting polymer as photothermal converter, PA emitter and iron-chelating Fenton catalyst. Upon photoirradiation, HSN generates heat not only to induce cytotoxicity but also to enhance Fenton reaction. The increased ·OH generation promotes both ferroptosis and apoptosis, oxidizes HSN (42 nm) and transforms it into tiny segments (1.7 nm) with elevated intratumoral permeability. The non-invasive seamless synergism leads to amplified therapeutic effects including a deep ablation depth (9 mm), reduced expression of metastasis-related proteins and inhibition of metastasis from primary tumor to distant organs. Thereby, our study provides a generalized nanozyme strategy to compensate both ferrotherapy and phototherapeutics for complete tumor regression.
SignificanceTumor cells reprogram their metabolism to support cell growth, proliferation, and differentiation, thus driving cancer progression. Profiling of the metabolic signatures in heterogeneous tumors facilitates the understanding of tumor metabolism and introduces potential metabolic vulnerabilities that might be targeted therapeutically. We proposed a spatially resolved metabolomics method for high-throughput discovery of tumor-associated metabolite and enzyme alterations using ambient mass spectrometry imaging. Metabolic pathway-related metabolites and metabolic enzymes that are associated with tumor metabolism were efficiently discovered and visualized in heterogeneous esophageal cancer tissues. Spatially resolved metabolic alterations hold the key to defining the dependencies of metabolism that are most limiting for cancer growth and exploring metabolic targeted strategies for better cancer treatment.
In order to promote imaging-guided chemotherapy for preclinical and clinical applications, endogenous nanosystems with both contrast and drug-delivery properties are highly desired. Here, the simple use of melanin is first reported, and this biopolymer with good biocompatibility and biodegradability, binding ability to drugs and ions, and intrinsic photoacoustic properties, can serve as an efficient endogenous nanosystem for imaging-guided tumor chemotherapy in living mice.
Cell‐membrane‐coated nanoparticles (CCNPs) that integrate the biophysiological advantages of cell membranes with the multifunctionalities of synthetic materials hold great promise in cancer immunotherapy. However, strategies have yet to be revealed to further improve their immunotherapeutic efficacy. Herein, a polymer multicellular nanoengager (SPNE) for synergistic second‐near‐infrared‐window (NIR‐II) photothermal immunotherapy is reported. The nanoengager consists of an NIR‐II absorbing polymer as the photothermal core, which is camouflaged with fused membranes derived from immunologically engineered tumor cells and dendritic cells (DCs) as the cancer vaccine shell. In association with the high accumulation in lymph nodes and tumors, the multicellular engagement ability of the SPNE enables effective cross‐interactions among tumor cells, DCs, and T cells, leading to augmented T cell activation relative to bare or tumor‐cell‐coated nanoparticles. Upon deep‐tissue penetrating NIR‐II photoirradiation, SPNE eradicates the tumor and induces immunogenic cell death, further eliciting anti‐tumor T cell immunity. Such a synergistic photothermal immunotherapeutic effect eventually inhibits tumor growth, prevents metastasis and procures immunological memory. Thus, this study presents a general cell‐membrane‐coating approach to develop photo‐immunotherapeutic agents for cancer therapy.
Discrete Pt(II) metallacycles have potential applications in biomedicine. Herein, we engineered a dual-modal imaging and chemo-photothermal therapeutic nano-agent 1 that incorporates discrete Pt(II) metallacycle 2 and fluorescent dye 3 (emission wavelength in the second near-infrared channel [NIR-II]) into multifunctional melanin dots with photoacoustic signal and photothermal features. Nano-agent 1 has a good solubility, biocompatibility, and stability in vivo. Both photoacoustic imaging and NIR-II imaging in vivo confirmed that 1 can effectively accumulate at tumor sites with good signal-to-background ratio and favorable distribution. Guided by precise dual-modal imaging, nano-agent 1 exhibits a superior antitumor performance and less severe side effects compared with a single treatment because of the high efficiency of the chemo-photothermal synergistic therapy. This study shows that nano-agent 1 provides a promising multifunctional theranostic platform for potential applications in biomedicine.
Whole-body molecular imaging is able to directly map spatial distribution of molecules and monitor its biotransformation in intact biological tissue sections. Imaging mass spectrometry (IMS), a label-free molecular imaging method, can be used to image multiple molecules in a single measurement with high specificity. Herein, a novel easy-toimplement, whole-body IMS method was developed with air flow-assisted ionization in a desorption electrospray ionization mode. The developed IMS method can effectively image molecules in a large whole-body section in open air without sample pretreatment, such as chemical labeling, section division, or matrix deposition. Moreover, the signal levels were improved, and the spatial assignment errors were eliminated; thus, high-quality whole-body images were obtained. With this novel IMS method, in situ mapping analysis of molecules was performed in adult rat sections with picomolar sensitivity under ambient conditions, and the dynamic information of molecule distribution and its biotransformation was provided to uncover molecular events at the whole-animal level. A global view of the differential distribution of an anticancer agent and its metabolites was simultaneously acquired in whole-body rat and model mouse bearing neuroglioma along the administration time. The obtained drug distribution provided rich information for identifying the targeted organs and predicting possible tumor spectrum, pharmacological activity, and potential toxicity of drug candidates.
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