Targeted delivery
of enzyme-activatable probes into cancer cells
to facilitate accurate imaging and on-demand photothermal therapy
(PTT) of cancers with high spatiotemporal precision promises to advance
cancer diagnosis and therapy. Here, we report a tumor-targeted and
matrix metalloprotease-2 (MMP-2)-activatable nanoprobe (T-MAN) formed
by covalent modification of Gd-doping CuS micellar nanoparticles with
cRGD and an MMP-2-cleavable fluorescent substrate. T-MAN displays
a high r
1 relaxivity (∼60.0 mM–1 s–1 per Gd3+ at 1 T)
and a large near-infrared (NIR) fluorescence turn-on ratio (∼185-fold)
in response to MMP-2, allowing high-spatial-resolution magnetic resonance
imaging (MRI) and low-background fluorescence imaging of gastric tumors
as well as lymph node (LN) metastasis in living mice. Moreover, T-MAN
has a high photothermal conversion efficiency (PCE, ∼70.1%)
under 808 nm laser irradiation, endowing it with the ability to efficiently
generate heat to kill tumor cells. We demonstrate that T-MAN can accumulate
preferentially in gastric tumors (∼23.4% ID%/g at 12 h) after
intravenous injection into mice, creating opportunities for fluorescence/MR
bimodal imaging-guided PTT of subcutaneous and metastatic gastric
tumors. For the first time, accurate detection and laser irradiation-initiated
photothermal ablation of orthotopic gastric tumors in intraoperative
mice was also achieved. This study highlights the versatility of using
a combination of dual biomarker recognition (i.e., αvβ3 and MMP-2) and dual modality imaging (i.e., MRI
and NIR fluorescence) to design tumor-targeting and activatable nanoprobes
with improved selectivity for cancer theranostics in vivo.
Eindringlinge: Der effiziente Transport von Antikrebswirkstoffen in Zellen gelingt mithilfe reversibel vernetzender Dextrannanopartikel, die unter reduktiven Bedingungen – wie sie im Zellinneren vorherrschen – schnell destabilisiert werden. Die Nanopartikel nehmen große Wirkstoffmengen auf, und sie können Doxorubicin nach Reduktion in vitro wie auch in Tumorzellen besonders im Zellkern freisetzen (siehe Schema).
Noninvasive physical treatment with relatively low intensity stimulation and the development of highly efficient anticancer medical strategy are still desirable for cancer therapy. Herein a versatile, biodegradable, hollow mesoporous organosilica nanocapsule (HMONs) nanoplatform that is capped by the gemcitabine (Gem) molecule through a pH-sensitive acetal covalent bond is designed. The fabricated nanocapsule exhibits desirable small molecule release at the tumor tissues/cell sites and shows a reduced risk for drug accumulation. After loading indocyanine green (ICG), the heatshock protein 90 (Hsp 90) inhibitor, and 17AAG and modification with polyethylene glycol (NH 2 -PEG), the resulting ICG−17AAG@HMONs−Gem−PEG exhibited a precisely controlled release of ICG and 17AAG and low-temperature photothermal therapy (PTT) (∼41 °C) with excellent tumor destruction efficacy. In addition, ICG loading conferred the nanoplatform with near-infrared fluorescence imaging (FL) and photoaccoustic (PA) imaging capability. In short, this work not only presents a smart drug self-controlled nanoplatform with pH-responsive payload release and theranostic performance but also provides an outstanding low-temperature PTT strategy, which is highly valid in the inhibition of cancer cells with minimal damage to the organism. Therefore, this research provides a paradigm that has a chemodrug-gated HMONsbased theranostic nanoplatform with intrinsic biodegradability, multimodal imaging capacity, high low-temperature PTT/ chemotherapy efficacy, and reduced systemic toxicity.
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