Novel nanomedicine with a chemical-exchange saturation transfer effect for breast cancer treatment in vivo

Abstract

BackgroundNanomedicine is a promising new approach to cancer treatment that avoids the disadvantages of traditional chemotherapy and improves therapeutic indices. However, the lack of a real-time visualization imaging technology to monitor drug distribution greatly limits its clinical application. Image-tracked drug delivery is of great clinical interest; it is useful for identifying those patients for whom the therapy is more likely to be beneficial. This paper discusses a novel nanomedicine that displays features of nanoparticles and facilitates functional magnetic resonance imaging but is challenging to prepare.ResultsTo achieve this goal, we synthesized an acylamino-containing amphiphilic block copolymer (polyethylene glycol-polyacrylamide-polyacetonitrile, PEG-b-P(AM-co-AN)) by reversible addition-fragmentation chain transfer (RAFT) polymerization. The PEG-b-P(AM-co-AN) has chemical exchange saturation transfer (CEST) effects, which enable the use of CEST imaging for monitoring nanocarrier accumulation and providing molecular information of pathological tissues. Based on PEG-b-P(AM-co-AN), a new nanomedicine PEG-PAM-PAN@DOX was constructed by nano-precipitation. The self-assembling nature of PEG-PAM-PAN@DOX made the synthesis effective, straightforward, and biocompatible. In vitro studies demonstrate decreased cytotoxicity of PEG-PAM-PAN@DOX compared to free doxorubicin (half-maximal inhibitory concentration (IC50), mean ~ 0.62 μg/mL vs. ~ 5 μg/mL), and the nanomedicine more efficiently entered the cytoplasm and nucleus of cancer cells to kill them. Further, in vivo animal experiments showed that the nanomedicine developed was not only effective against breast cancer, but also displayed an excellent sensitive CEST effect for monitoring drug accumulation (at about 0.5 ppm) in tumor areas. The CEST signal of post-injection 2 h was significantly higher than that of pre-injection (2.17 ± 0.88% vs. 0. 09 ± 0.75%, p < 0.01).ConclusionsThe nanomedicine with CEST imaging reflects the characterization of tumors and therapeutic functions has great potential medical applications.

Glutamate Chemical Exchange Saturation Transfer (GluCEST) Magnetic Resonance Imaging in Pre-clinical and Clinical Applications for Encephalitis

“…Chemical exchange saturation transfer (CEST) is a relatively novel MR molecular imaging approach that utilizes a frequency selective radiofrequency (RF) irradiation pulse on particular exchangeable protons (e.g., hydroxyls, amides, and amines), thus resulting in attenuated water signals that can be measured via the loss of water signal intensity to indirectly characterize the microenvironment of the solution (Ward et al, 2000;Li et al, 2017). CEST MRI has several advantages (Wu et al, 2015;Jia et al, 2019;Wang et al, 2019), as follows: (1) it allows amplified detection of low concentration agents; (2) it can be switched "on" and "off " at will by adjusting the RF irradiation pulse parameters;…”

“…Chemical exchange saturation transfer (CEST) is a relatively novel MR molecular imaging approach that utilizes a frequency selective radiofrequency (RF) irradiation pulse on particular exchangeable protons (e.g., hydroxyls, amides, and amines), thus resulting in attenuated water signals that can be measured via the loss of water signal intensity to indirectly characterize the microenvironment of the solution ( Ward et al, 2000 ; Li et al, 2017 ). CEST MRI has several advantages ( Wu et al, 2015 ; Jia et al, 2019 ; Wang et al, 2019 ), as follows: (1) it allows amplified detection of low concentration agents; (2) it can be switched “on” and “off” at will by adjusting the RF irradiation pulse parameters; (3) it has the potential to provide metabolite information from biological tissues as well as anatomical features; (4) it has high spatial resolution, is non-invasive, and does not require the injection of contrast agents; and (5) it can be specifically tailored to respond to a given stimulus (e.g., pH, enzyme, temperature, metabolite levels, etc.). Given these advantages and good performance, CEST MRI has received much attention and is now widely used in preclinical and clinical research.…”

Synergistic inhibition of metastatic breast cancer by dual-chemotherapy with excipient-free rhein/DOX nanodispersions

“…Thus, the efficient co-delivery of multiple therapeutic agents to a target tissue with a controlled dose ratio and synergistic efficacy is highly desirable for future clinical translation. To address this need, many nanosized co-delivery architectures, such as liposomes [12], micelles [13,14], mesoporous silica nanoparticles [15] and hydrogel [16], have been reported. For instance, the all-in-one brush-arm star polymer nanoparticles (NPs) were designed by ring-opening metathesis polymerization, which could generate precise molar ratios of doxorubicin (DOX), camptothecin and cisplatin.…”

Synergistic inhibition of metastatic breast cancer by dual-chemotherapy with excipient-free rhein/DOX nanodispersions

“…Thus, the e cient codelivery of multiple therapeutic agents to a target tissue with a controlled dose ratio and synergistic e cacy is highly desirable for future clinical translation. Many nanosized codelivery architectures, such as liposomes [14], micelles [15,16], mesoporous silica nanoparticles [17] and hydrogels [18], have been reported to address this need. For instance, the all-in-one brush-arm star polymer nanoparticles (NPs) were designed by ring-opening metathesis polymerization, which generated precise molar ratios of doxorubicin (DOX) [19], camptothecin [20] and cisplatin [21].…”