Cascade-Promoted Photo-Chemotherapy against Resistant Cancers by Enzyme-Responsive Polyprodrug Nanoplatforms

Abstract

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.

Boosting Non‐Radiative Decay to Do Useful Work: Development of a Multi‐Modality Theranostic System from an AIEgen

“…At 12 hp ost-injection, the PA signal was much weaker than that of 3h post-injection, indicating the almost complete clearance of the TFM NPs. [34] After intravenous injection with TFM NPs sized % 72 nm for 4h,t he tumor fluorescence was much more significant than that of TFM NPs sized % 180 nm (Figure S20 a). [32,33] These results solidly demonstrated that TFM NPs possess ap rominent EPR effect, enabling them to efficiently accu-mulate in tumor tissue combined with rapid clearance,t hus making them excellent agents for PA Ii nahigh-contrast and safe manner.…”

“…Thei nvivo biodistribution of the TFM NPs was examined by encapsulating slightly fluorescent indocyanine green (ICG). [34] After intravenous injection with TFM NPs sized % 72 nm for 4h,t he tumor fluorescence was much more significant than that of TFM NPs sized % 180 nm (Figure S20 a). Them ore efficient tumor accumulation of TFM NPs with as ize of % 72 nm was also confirmed by ex vivo fluorescence imaging of isolated tissues (Figure S20 b,c), indicating that the tumor accumulation potency of the TFM NPs with as maller size was superior,w hich was optimized for efficient theranostics.…”

<p>Applications of Inorganic Nanomaterials in Photothermal Therapy Based on Combinational Cancer Treatment</p>

“…Upon cellular uptake in lysosomes, ICG could induce local hyperthermia and ROS under NIR light irradiation and it could also assist the escape of cisplatin prodrugs into the reductive cytosol by damaging lysosomes. 34 In addition, the combination treatment of PDT can benefit from pathogen inhibition. Liu et al developed azonia-containing polyelectrolytes with extraordinary performance for ROS generation for antibacterial applications.…”

Boosting Non‐Radiative Decay to Do Useful Work: Development of a Multi‐Modality Theranostic System from an AIEgen

“…Furthermore, it was observed that the size of the TFM NPs can be increased to ≈180 nm by enhancing the feed content of TFM and PEG‐ b ‐PLA in the formation of the TFM NPs (Figure S19). The in vivo biodistribution of the TFM NPs was examined by encapsulating slightly fluorescent indocyanine green (ICG) . After intravenous injection with TFM NPs sized ≈72 nm for 4 h, the tumor fluorescence was much more significant than that of TFM NPs sized ≈180 nm (Figure S20 a).…”