Red/Near‐Infrared Emissive Metalloporphyrin‐Based Nanodots for Magnetic Resonance Imaging‐Guided Photodynamic Therapy In Vivo

Near‐infrared emissive (NIR) porphyrin‐implanted carbon nanodots (PCNDs or MPCNDs) are prepared by selectively carbonization of free base or metal complexes [M = Zn(II) or Mn(III)] of tetra‐(meso‐aminophenyl)porphyrin in the presence of citric acid. The as‐prepared nanodots exhibit spontaneously NIR emission, small size, good aqueous dispersibility, and favorable biocompatibility characteristic of both porphyrins and pristine carbon nanodots. The subcellular localization experiment of nanodots indicates a lysosome‐targeting feature. And the in vitro photodynamic therapy (PDT) results on HeLa cells indicate the nanodots alone have no adverse effect on tumor cells, but display remarkable photodynamic efficacy upon irradiation. Moreover, MnPCNDs containing paramagnetic Mn(III) ions, which possesses good biocompatibility, NIR luminescence, and magnetic resonance imaging and efficient singlet oxygen production, are further studied in magnetic resonance imaging‐guided photodynamic therapy in vivo.     

Tumor‐Targeting W18O49 Nanoparticles for Dual‐Modality Imaging and Guided Heat‐Shock‐Response‐Inhibited Photothermal Therapy in Gastric Cancer

Photothermal therapy (PTT) is an emerging noninvasive and precise localized therapeutic modality; however, it is deeply limited by its poor tumor accumulation, inadequate photothermal conversion efficiency, and the thermoresistance of cancer cells. Aimed at these shortcomings, tumor‐targeting nanoparticles (iRGD‐W₁₈O₄₉‐17AAG) comprising carboxyl‐group‐functionalized W₁₈O₄₉ nanoparticles, integrin‐targeting peptide iRGD, and HSP90‐inhibitor 17AAG are developed. The W₁₈O₄₉ nanoparticles act as excellent PTT carriers and computed tomography (CT) imaging contrast agents. The ring type polypeptide iRGD promotes the accumulation of nanoparticles in the tumour and further penetration into cancer cells. The introduction of 17AAG can inhibit the heat‐shock response and overcome the thermoresistance, thus increasing the curative effect of PTT and reducing the chance of tumor recurrence. The W₁₈O₄₉ nanoparticles can also be used to monitor and guide the phototherapeutic through CT and near‐infrared fluorescence imaging after modification with Cy5.5. In addition, superior biosafety is also indicated in both preliminary in vitro and in vivo assessments. The potential of iRGD‐W₁₈O₄₉‐17AAG in tumor targeting, dual modality imaging‐guided and remarkable enhanced PTT of gastric cancer with ignorable side effect both in vitro and in vivo, which may be further applied in clinic, is highlighted.     

Therapeutic Pretargeting with Gold Nanoparticles as Drug Candidates for Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) is a binary approach for cancer treatment in which boron-10 atoms and thermal neutrons need to colocalize to become effective. Recent research in the development of BNCT drug candidates focuses increasingly on nanomaterials, with the advantages of high boron loadings and passive targeting due to the enhanced permeability and retention (EPR) effect. The use of small boron-rich gold nanoparticles (AuNPs) in combination with a pretargeting approach is proposed. Small sized polyethylene glycol–stabilized AuNPs (core size 4.1 ± 1.5 nm), are synthesized and functionalized with thiolated cobalt bis(dicarbollide) and tetrazine. To enable in vivo tracking of the AuNPs by positron emission tomography (PET), the core is doped with [⁶⁴Cu]CuCl₂. For the pretargeting approach, the monoclonal antibody Trastuzumab is functionalized with trans-cyclooctene-N-hydroxysuccinimide ester. After proving in vitro occurrence of the antibody conjugation onto the AuNPs by click reaction and the low toxicity of the AuNPs, the boron delivery system is evaluated in vivo using breast cancer xenograft bearing mice and PET imaging. Tumor uptake due to the EPR effect can be witnessed with ≈5% injected dose (ID) cm⁻³ at 24 h postinjection, but with slower clearance than expected. Therefore, no increased retention can be observed using the pretargeting strategy.     

Hydrophilic Cu3BiS3 Nanoparticles for Computed Tomography Imaging and Photothermal Therapy

Hydrophilic Cu₃BiS₃ nanoparticles (NPs) have been prepared using the thermal decomposition of precursor complexes in oily‐mixed solvent followed by coating the produced Cu₃BiS₃ NPs with polyvinylpyrrolidone (PVP). The resulting Cu₃BiS₃/PVP NPs remain stable in aqueous solutions over a long period of time, and meanwhile, they show low in vitro cytotoxicity and negligible toxicity to mice in vivo. Cu₃BiS₃/PVP NPs could operate as an efficient dual‐modal contrast agent to simultaneously enhance X‐ray computed tomography imaging and photothermal imaging of tumor model in vivo. Moreover, highly efficient ablation of cancer cells both in vitro and in vivo has been successfully achieved by combining Cu₃BiS₃/PVP NPs with near‐infrared (NIR) laser irradiation. All of the positive results in this study highlight that Cu₃BiS₃/PVP NPs could serve as a promising platform for cancer diagnosis and therapy.