Fluorescence intensity (upper panel) and lifetime (bottom panel) images of KB cells stained with FITC (B), Si NPs (C) and unstained control (A).

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Cisplatin has long been the first-line treatment for a variety of solid tumors. However, the poor pharmacokinetics and intrinsic or acquired drug resistance are the main challenges in cancer therapy. Herein, endogenous enzymeresponsive cisplatin polyprodrug nanoplatforms were developed for cascade-promoted photo-chemotherapy against drugresistant cancers. The polyprodrug nanoplatforms, ICG/Poly(Pt), were fabricated from the indocyanine green (ICG) photosensitizer and cisplatin polyprodrug amphiphiles, PEG-b-P(Ptco-GFLG)-b-PEG, consisting of repeated enzyme-degradable GFLG peptides and cisplatin prodrug units in the hydrophobic block and hydrophilic PEG chains, exhibiting ∼24.7 wt % cisplatin loading. Upon cellular uptake in lysosomes, cathepsin B could partially degrade the nanoplatforms into cisplatin prodrug, and then 808 nm laser irradiation would excite ICG to afford reactive oxygen species (ROS) and local hyperthermia, thus launching the phototherapy. Furthermore, the concurrent photodynamic and photothermal process could damage lysosomes to accelerate the cytosolic movement of the cisplatin prodrug away from lysosomes, which was followed by GSH reduction into active cisplatin to initiate cascade chemotherapy. In addition, the polyprodrug nanoplatforms provided dual-model photoacoustic and fluorescence imaging to guide the therapeutic treatments. In vitro and in vivo explorations proved that ICG/Poly(Pt) could significantly inhibit the cisplatin-resistant A549/DDP cancers. The well-defined polyprodrug nanoplatforms exhibited great potential for imaging-guided cascade treatments of resistant cancers in intelligent biomedicine.

Targeting peptide-modified magnetic graphene-based mesoporous silica (MGMSPI) are synthesized, characterized, and developed as a multifunctional theranostic platform. This system exhibits many merits, such as biocompatibility, high near-infrared photothermal heating, facile magnetic separation, large T2 relaxation rates (r2), and a high doxorubicin (DOX) loading capacity. In vitro and in vivo results demonstrate that DOX-loaded MGMSPI (MGMSPID) can integrate magnetic resonance imaging, dual-targeting recognition (magnetic targeting and receptor-mediated active targeting), and chemo-photothermal therapy into a single system for a visualized-synergistic therapy of glioma. In addition, it is observed that the MGMSPID system has heat-stimulated, pH-responsive, sustained release properties. All of these characteristics would provide a robust multifunctional theranostic platform for visualized glioma therapy.

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