Radio- and Photosensitizing Os(II)-Based Nanocage for Combined Radio-/Chemo-/X-ray-Induced Photodynamic Therapies, NIR Imaging, and Drug Delivery

Abstract

Integration of clinical imaging and collaborative multimodal therapies into a single nanomaterial for multipurpose diagnosis and treatment is of great interest to theranostic nanomedicine. Here, we report a rational design of a discrete Os-based metal–organic nanocage Pd6(OsL3)8 28+ (MOC-43) as a versatile theranostic nanoplatform to meet the following demands simultaneously: (1) synergistic treatments of radio-, chemo-, and X-ray-induced photodynamic therapies (X-PDT) for breast cancer, (2) NIR imaging for cancer cell tracking and tumor-targeting, and (3) anticancer drug transport through a host–guest strategy. The nanoscale MOC-43 incorporates high-Z Os-element to interact with X-ray irradiation for dual radiosensitization and photosensitization, showing efficient energy transfer to endogenous oxygen in cancer cells to enhance X-PDT efficacy. It also features intrinsic NIR emission originating from metal-to-ligand charge transfer (MLCT) as an excellent imaging probe. Meanwhile, its 12 pockets can capture and concentrate low-water-soluble molecules for anticancer drug delivery. These multifunctions are implemented and demonstrated by micellization of coumarin-loaded cages with DSPE-PEG2000 into coumarin ⊂ MOC-43 nanoparticles (CMNPs) for efficient subcellular endocytosis and uptake. The cancer treatments in vitro/in vivo show promising antitumor performance, providing a conceptual protocol to combine cage-cargo drug transport with diagnosis and treatment for collaborative cancer theranostics by virtue of multifunction synergism on a single-nanomaterial platform.

Facile synthesis of an acid-responsive cinnamaldehyde-pendant polycarbonate for enhancing the anticancer efficacy of etoposide via glutathione depletion

“…Coumarin 6 (C6), a fluorescent probe, is widely used to monitor nanoparticle-based drug delivery via fluorescence confocal microscopy, as cellular internalization is critical for drug efficacy. 25 To investigate the intracellular distribution of nanoparticles, C6@PCA was prepared through dialysis, with a C6 loading of approximately 0.5% (w/w) in the nanoparticles. Cellular localization was evaluated using laser confocal microscopy after incubating 4T1 cells with C6@PCA for 1, 3, and 5 hours, respectively.…”

Dynamic Stereochemistry of M8Pd6 Supramolecular Cages Based on Metal‐Center Lability for Differential Chiral Induction, Resolution, and Recognition

“…Totally 24 BINOLs are dually packed in the 12 chiral pockets of the cage, where the guests are captured through the O−H⋅⋅⋅N hydrogen bonds between BINOL and imidazole‐N, as well as the cage‐guest and guest‐guest π‐π stacking interactions (Figures 4a, S50–55 and Table S14–16). All Ru/Ni/Fe/Zn‐cages are competent for this kind of host–guest chiral selection [6c,16–17,26] …”

“…All Ru/Ni/Fe/Zn-cages are competent for this kind of host-guest chiral selection. [6c, [16][17]26] As the solvent conditions are able to influence crystallization process and host-guest interactions, [3a,16,27] we also tried co-crystallization in an Et 2 OÀ CH 3 CN solvent system (Figures 1, S56-59 and Tables S17-18). Strikingly, the same chiral guest inducers present reverse host-guest recognition behaviors, [6c,16] i.e., the R-BINOL guests choose to cocrystallize with Λ 8 À M 8 Pd 6 , while the S-BINOL guests select Δ 8 À M 8 Pd 6 .…”