Construction of Intelligent Responsive Drug Delivery System and Multi-Mode Imaging Based on Gold Nanodots.

Cancer remains a formidable global problem with a high mortality rate. There are many effective anti-cancer drugs in clinical use, among which paclitaxel (PTX) has good effects on non-small cell lung cancer, ovarian cancer, and breast cancer. However, when applied to the clinic, PTX still has many limitations, such as poor water solubility, drug resistance, and side effects on healthy tissues. A gold nanodots-paclitaxel-polylysine (AuNDs-PTX-PLL) core-shell nano-system of integrated diagnosis and treatment is constructed to achieve intelligent responsive drug delivery. On the one hand, the problem of poor water-solubility and drug resistance of PTX are solved. On the other hand, the nano-system has an excellent intelligent response effect. Drugs can only be released in the weakly acidic environment of the tumor, which reduces the damage and side effects to normal tissues. Moreover, the nano-system can be used for real-time tracking and auxiliary diagnosis for the tumor through the multi-mode imaging mode, such as fluorescence, photoacoustic, and computed tomography to achieve accurate visualization. The photothermal effect of AuNDs is beneficial to promote the release of drugs. The nano-system integrates multi-mode imaging, chemotherapy, intelligent drug release in tumor weakly acidic environment, and has excellent practical application prospects in tumor diagnosis and treatment.

Multifunctional nanoprobe for multi-mode imaging and diagnosis of metastatic prostate cancer.

The high incidence and complex subtypes of prostate cancer put forward higher requirements for accurate diagnosis. Furthermore, advanced prostate cancer is prone to metastasis. Single biological imaging mode faces a challenge of sensitive and fast bioimaging of metastasic prostate cancer. Thus, exploring a nanoprobe with multi-mode imaging function has an important impact on preoperative imaging and intraoperative visualization guide of metastatic prostate cancer. Herein, based on the optical properties and X-ray attenuation capability of Au nanodots as well as the slow electronic relaxation of Gd3+, we designed and fabricated the multifunctional nanoprobe Au/Gd nanodots for multi-mode imaging and accurate diagnosis of bone metastatic prostate cancer. The results showed that multiple imaging modes complement each other to achieve high-precision of metastasic prostate cancer detection and accurately guide treatment. In addition, in vitro/vivo experiments showed that Au/Gd nanodots had good biocompatibility and biosafety. Therefore, the prepared multifunctional nanoprobe may provide new strategies and insights for precise diagnosis of metastatic prostate cancer in clinical practice.

Multifunctional nano-system for multi-mode targeted imaging and enhanced photothermal therapy of metastatic prostate cancer.

Prostate cancer (PCa) routinely employs magnetic resonance (MR) imaging, while metastatic PCa needs more complicated detection methods for precise localization. The inconvenience of using different methods to detect PCa and its metastases in patients and the limitations of single-mode imaging have brought great challenges to clinicians. Meanwhile, clinical treatments for metastatic PCa are still limited. Herein, we report a targeted theranostic platform of Au/Mn nanodots-luteinising hormone releasing hormone (AMNDs-LHRH) nano-system for multi-mode imaging guided photothermal therapy of PCa. The nano-system not only can simultaneously target Gonadotropin-Releasing Hormone Receptor (GnRH-R) positive PCa and its metastases for accurate preoperative CT/MR diagnosis, but also possesses fluorescence (FL) visualization navigated surgery, demonstrating its potential application in clinical cancer detection and surgery guidance. Meanwhile, the AMNDs-LHRH with promising targeting and photothermal conversion ability significantly improve the photothermal therapy effect of metastatic PCa. The AMNDs-LHRH nano-system guarantees the diagnostic accuracy and enhanced therapeutic effect, which provides a promising platform for clinical diagnosis and treatment of metastatic PCa. STATEMENT OF SIGNIFICANCE: Accurate clinical diagnosis and treatment of prostate cancer and its metastases is challenging. A targeted theranostic platform of AMNDs-LHRH nano-system for multi-mode imaging (FL/CT/MR) guided photothermal therapy of metastatic prostate cancer has been reported. The nano-system not only can simultaneously target prostate cancer and its metastases for accurate preoperative CT/MR diagnosis, but also possesses fluorescence visualization navigated surgery, demonstrating its potential application in clinical cancer detection and surgery guidance. The nano-system with great targeting and photothermal conversion ability significantly improve the photothermal therapy effect of metastatic prostate cancer. Overall, the AMNDs-LHRH nano-system integrates tumor targeting, multi-mode imaging and enhanced therapeutic effect, which can provide an effective strategy for the clinical diagnosis and treatment of metastatic PCa.

AuNCs-LHRHa nano-system for FL/CT dual-mode imaging and photothermal therapy of targeted prostate cancer.

As the most common cancer in men worldwide, prostate cancer has a serious impact on people's health. Until now, the development of a platform for integrating tumor targeting, imaging and an effective treatment for prostate cancer has remained challenging. Herein, a nano-system is designed to improve both diagnosis and treatment for prostate cancer. We successfully synthesized an AuNCs-LHRHa nano-system by combining PEI-modified gold nanoclusters (AuNCs) with LHRH analogues (LHRHa). Due to the good tunable optical properties and photothermal properties of AuNCs, the nano-system can not only achieve efficient fluorescence/computed tomography dual-mode imaging, but can also be used for photothermal therapy (PTT). After modifying the LHRHa antibody of a prostate tumor, AuNCs-LHRHa can be more effectively recognized by the gonadotropin-releasing hormone receptors (GnRH-R) on the membrane of RM-1 cells, enhancing the tumor cell uptake of the nano-system, improving the targeting accuracy and PTT therapy efficacy for prostate cancer. It is hoped that the nano-system, which combines dual-mode imaging and targeted therapy, will provide a promising strategy for the integration of FL/CT diagnosis and PTT therapy for GnRH-R positive prostate cancer.