Codelivery of CuS and DOX into Deep Tumors with Size and Charge-Switchable PAMAM Dendrimers for Chemo-photothermal Therapy.

Accurate targeting of therapeutic agents to specific tumor tissues, especially via deep tumor penetration, has been an effective strategy in cancer treatments. Here, we described a flexible nanoplatform, pH-responsive zwitterionic acylsulfonamide betaine-functionalized fourth-generation PAMAM dendrimers (G4-AB), which presented multiple advantages for chemo-photothermal therapy, including template synthesis of ultrasmall copper sulfide (CuS) nanoparticles and further encapsulation of doxorubicin (DOX) (G4-AB-DOX/CuS), long-circulating performance by a relatively large size and zwitterionic surface in a physiological environment, combined size shrinkage, and charge conversions via pH-responsive behavior in an acidic tumor microenvironment (TME). Accordingly, high tumor penetration and positive cell uptake for CuS and DOX have been determined, which triggered an excellent combination treatment under near-infrared irradiation in comparison to the monochemotherapy system and irresponsive chemo-photothermal system. Our study represented great promise in constructing multifunctional carriers for the effective delivery of photothermal nanoparticles and drugs in chemo-photothermal therapy.

Octopod PtCu Nanoframe for Dual-Modal Imaging-Guided Synergistic Photothermal Radiotherapy.

Heavy atom nanoparticles have high X-ray absorption capacity and near infrared (NIR) photothermal conversion efficiency, which could be used as radio-sensitizers. We hypothesized that concave PtCu octopod nanoframes (OPCNs) would be an efficient nanoplatform for synergistic radio-photothermal tumor ablation. Methods: In this study, we newly exploited a folic acid-receptor (FR) mediated photothermal radiotherapy nanoagent base on OPCNs. OPCNs were synthesized with a hydrothermal method and then modified with polyethylene glycol (PEG) and folic acid (FA). A series of physical and chemical characterizations, cytotoxicity, targeting potential, endocytosis mechanism, biodistribution, systematic toxicological evaluation, pharmacokinetics, applications of OPCNs-PEG-FA for in vitro and in vivo infrared thermal imaging (ITI)/photoacoustic imaging (PAI) dual-modal imaging and synergistic photothermal radiotherapy against tumor were carried out. Results: The OPCNs-PEG-FA demonstrated good biocompatibility, strong NIR absorption and X-ray radio-sensitization, which enabling it to track and visualize tumor in vivo via ITI/PAI dual-modal imaging. Moreover, the as-synthesized OPCNs-PEG-FA exhibited remarkable photothermal therapy (PTT) and radiotherapy (RT) synergistic tumor inhibition when treated with NIR laser and X-ray. Conclusion: A novel multifunctional theranostic nanoplatform based on OPCNs was designed and developed for dual-modal image-guided synergistic tumor photothermal radiotherapy.

Drug "Pent-Up" in Hollow Magnetic Prussian Blue Nanoparticles for NIR-Induced Chemo-Photothermal Tumor Therapy with Trimodal Imaging.

The study reports a biocompatible smart drug delivery system based on a doxorubicin (DOX) blending phase-change material of 1-pentadecanol loaded hollow magnetic Prussian blue nanoparticles, resulting in HMNP-PB@Pent@DOX. The system possesses concentration-dependent high thermogenesis (>50 °C) when applying a near-infrared (NIR) laser irradiation only for 5 min. Furthermore, the system realizes near "zero release" of drug and is efficiently triggered by NIR for drug delivery in an "on" and "off" manner, thus inducing cell apoptosis in vitro and in vivo. Moreover, the system clearly indicates tumor site with trimodal imaging of magnetic resonance imaging, photoacoustic tomography imaging, and infrared thermal imaging. Furthermore, the system achieves efficient chemo-photothermal combined tumor therapy in vivo with 808 nm laser irradiation for 5 min at 1.2 W cm-2 , revealing the good tumor inhibition effect comparing with those of chemotherapy or photothermal therapy alone. The system is also confirmed to be biocompatible in regard to the mortality rate.