Tumor-Microenvironment-Activated NIR-II Nanotheranostic Platform for Precise Diagnosis and Treatment of Colon Cancer

Abstract

Rational design of tumor-microenvironment (TME)activated nanoformulation for precisely targeted cancer treatment has recently attracted an enormous attention. However, the all-in-one TME-activated theranostic nanosystems with a simple preparation and high biocompatibility are still rarely reported. Herein, catalase nanocrystals (CatCry) are first introduced as a tumor microenvironment activatable nanoplatform for selective theranostics of colon cancer. They are engaged as (i) a "nanoreactor" for silver nanoparticles (AgNP) synthesis, (ii) a nanovehicle for tumor delivery of anticancer drug doxorubicin (DOX), and (iii) an in situ O 2 generator to relief tumor hypoxia. When CatCry-AgNP-DOX nanoformulation is within a tumor, the intratumoral H 2 S turns AgNP into Ag 2 S nanoparticles, inducing a photothermal effect and NIR-II emission under 808 nm laser irradiation and also triggering DOX release. Simultaneously, CatCry catalyzes intratumoral H 2 O 2 into O 2 , relieving hypoxia and enhancing chemotherapy. In contrast, when delivered to healthy tissue without increased concentration of H 2 S, the developed nanoformulation remains in the "off" state and no theranostic action takes place. Studies with colon cancer cells in vitro and a murine colon cancer model in vivo demonstrated that CatCry-AgNP-DOX delivered a synergistic combination of PTT and enhanced chemotherapy, enabling complete eradication of tumor with minimal side effects. This work not only introduces nanoplatform for theranostics of H 2 S-rich tumors but also suggests a general strategy for protein-crystal-based nanomedicine.

Hemoglobin Nanocrystals for Drugs Free, Synergistic Theranostics of Colon Tumor

“…[ 38 ] To confirm this assumption, Na 2 S was employed to simulate the interaction of tumor‐abundant H 2 S with protein nanocrystals. [ 17 ] As it is illustrated by the TEM images (Figure 1b), HbC degraded after the addition of Na 2 S, and a clear S element mapping showed up, correlating with the original Fe, O element distribution and confirming that the S element is associated with HbC after the reaction. In addition, a clear lattice pattern with a spacing of 0.097 nm is observed in the high‐resolution TEM (HRTEM) image, which can be well assigned to the (104) lattice fringes of Fe 1− x S. [ 39,40 ] The HRTEM image of Fe 1− x S nanoparticle resulted from HbC and Na 2 S reaction is shown in Figure S6, Supporting Information.…”

“…As has been illustrated in Figures 1 and 2 and Figure S6, Supporting Information, Fe 1−x S nanoparticles (nanocrystals) are generated as a result of the reaction between HbC and Na 2 S, which is used as a substitute of H 2 S, a known trigger in TMEactivated tumor theranostics. [17,44] It is also well documented that Fe 1−x S can serve as an MRI contrast and photothermal agent. [45,46] Thus, it is natural to suggest that HbC can also be employed as H 2 S activated agent for MRI-guided PTT.…”

“…[ 16 ] Furthermore, we reported a CatCry‐based theranostic nanoplatform that integrated tumor microenvironment (TME) activated NIR photothermal effect, NIR imaging, tumor hypoxia relief, and controlled release of chemotherapeutic drug to achieve synergetically enhanced, a highly specific and efficient combination of chemo and photothermal therapies of colon cancer. [ 17 ] While the obtained results suggest a general strategy of protein crystals as smart drug delivery nanosystems, the proposed nanocarriers still require drug loading for efficient cancer therapy, which is unavoidably associated with a possibility of off‐tumor drug release and corresponding toxicity for healthy tissues. At the same time, protein crystals themselves can be engineered to achieve the desired cancer theranostics, though the related reports are quite rare.…”

Implications of hydrogen sulfide in colorectal cancer: Mechanistic insights and diagnostic and therapeutic strategies

“…It is worth noting that the tedious preparation steps, the introduction of toxic reagents, and uncertain long-term toxicity may cause unpredictable limitations to the clinical application of nanocarriers [ 245 ]. Zhou et al introduced catalase nanocrystals (CatCry) as a TME-activated nanoplatform into the CRC treatment and prepared a nanoformulation (CatCry-AgNP-DOX) by a one-step co-crystallization method using catalase, AgNO 3 , and DOX as substrates [ 246 ]. The CatCry-AgNP-DOX nanoformulation reacted in situ to form Ag 2 S nanoparticles under the action of large amounts of H 2 S in the tumor, which provided NIR-I-activated photothermal effects and NIR-II imaging capabilities while triggering the release of loaded DOX chemotherapeutics.…”

Recent Progress in Second Near-Infrared (NIR-II) Fluorescence Imaging in Cancer

“…NIR-II fluorescence imaging is expected to provide great help for precise cancer identification and location. Additionally, cancer diagnosis can be combined with phototherapy to achieve the integration of cancer diagnosis and treatment, improving the efficiency and accuracy of cancer therapy [ 17 , 18 ]. In this review, we attempt to summarize the recent advances of NIR-II fluorescence imaging in cancer diagnosis and theranostics ( Figure 1 )and discuss the current challenges as well as perspectives for the near future.…”